Application evaluation of cardiopulmonary exercise test to guide comprehensive pulmonary rehabilitation in patients with pneumoconiosis / 环境与职业医学

Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO2/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO2), maximum metabolic equivalent (METs), and maximum work (Wmax). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO2/kg, AT, EqCO2, METs, or Wmax between the two groups (P>0.05). At the end of the trail, the indicators like pVO2/kg [(19.81±2.38) mL·(min·kg)−1], AT [(14.48±2.33) mL·(min·kg)−1], METs (5.64±0.69), and Wmax [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)−1, (11.70±1.94) mL·(min kg)−1, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO2 between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.

Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

Mechanism of Qizhu Kang'ai Prescription for Inhibiting Proliferation of Hepatocellular Carcinoma by Regulating Tumor Metabolic Reprogramming via PCK1/Akt/p21 Signal Axis / 中国实验方剂学杂志

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl4） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G0/G1 phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G0/G1 phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Eye diseases associated with developmental abnormality of neural crest / 国际眼科杂志(Guoji Yanke Zazhi)

The neural crest represents a dynamic population of embryonic stem cells, playing a pivotal role in the development of the eye. Through interactions with the surrounding neuroectoderm, superficial ectoderm and mesoderm, the neural crest contributes to the formation of numerous ocular structures, encompassing the corneal stroma and endothelium, trabecular meshwork, iris stroma, ciliary muscle, vitreous and choroidal vessels, and Müller cells. Aberrant migration and development of neural crest cells within the eye can instigate a complex series of ocular diseases. Such diseases include anterior segment like Axenfeld-Rieger syndrome, Peters anomaly, aniridia, primary congenital glaucoma, and Nail-Patella syndrome. Defects that impact the posterior segment may lead to CHARGE syndrome and Branchio-oculo-facial syndrome. Further, rare neurocristopathies such as Waardenburg syndrome, Treacher-Collins syndrome, and Char syndrome can also present with ocular abnormalities. In this review, we explore the ocular diseases that arise from abnormal neural crest cell development, and delve into the related genes involved in neural crest migration and development. We further discuss how mutations and defects in these genes can precipitate ocular diseases.

Construction and application value of CT based radiomics model in predicting the prognosis of patients with gastric neuroendocrine neoplasm / 中华消化外科杂志

Objective:To construct of a computed tomography (CT) based radiomics model for predicting the prognosis of patients with gastric neuroendocrine neoplasm (GNEN) and inves-tigate its application value.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 182 patients with GNEN who were admitted to 2 medical centers, including the First Affiliated Hospital of Zhengzhou University of 124 cases and the Affiliated Cancer Hospital of Zhengzhou University of 58 cases, from August 2011 to December 2020 were collected. There were 130 males and 52 females, aged 64(range, 56-70)years. Based on random number table, all 182 patients were divided into the training dataset of 128 cases and the validation dataset of 54 cases with a ratio of 7:3. All patients underwent enhanced CT examination. Observation indicators: (1) construction and validation of the radiomics prediction model; (2) analysis of prognostic factors for patients with GNEN in the training dataset; (3) construction and evaluation of the prediction model for prognosis of patients with GNEN. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and the chi-square test, corrected chi-square test or Fisher exact probability were used for comparison between groups. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. The R software (version 4.0.3) glmnet software package was used for least absolute shrinkage and selection operator (LASSO)-COX regression analysis. The rms software (version 4.0.3) was used to generate nomogram and calibration curve. The Hmisc software (version 4.0.3) was used to calculate C-index values. The dca.R software (version 4.0.3) was used for decision curve analysis. Results:(1) Construction and valida-tion of the radiomics prediction model. One thousand seven hundred and eighty-one radiomics features were finally extracted from the 182 patients. Based on the feature selection using intra-group correlation coefficient >0.75, and the reduce dimensionality using LASSO-COX regression analysis, 14 non zero coefficient radiomics features were finally selected from the 1 781 radiomics features. The radiomics prediction model was constructed based on the radiomics score (R-score) of these non zero coefficient radiomics features. According to the best cutoff value of the R-score as -0.494, 128 patients in the training dataset were divided into 64 cases with high risk and 64 cases with low risk, 54 patients in the validation dataset were divided into 35 cases with high risk and 19 cases with low risk. The area under curve (AUC) of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the training dataset was 0.83[95% confidence interval ( CI ) as 0.76-0.87, P<0.05], 0.84(95% CI as 0.73-0.91, P<0.05), 0.91(95% CI as 0.78-0.95, P<0.05), respectively. The AUC of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the validation dataset was 0.84(95% CI as 0.75-0.92, P<0.05), 0.84 (95% CI as 0.73-0.91, P<0.05), 0.86(95% CI as 0.82-0.94, P<0.05), respectively. (2) Analysis of prognostic factors for patients with GNEN in the training dataset. Results of multivariate analysis showed gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression were independent factors influencing prognosis of patients with GNEN in the training dataset ( P<0.05). (3) Construction and evaluation of the prediction model for prognosis of patients with GNEN. The clinical prediction model was constructed based on the independent factors influen-cing prognosis of patients with GNEN including gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression. The C-index value of clinical prediction model in the training dataset and the validation dataset was 0.86 (95% CI as 0.82-0.90) and 0.80(95% CI as 0.72-0.87), respectively. The C-index value of radiomics prediction model in the training dataset and the validation dataset was 0.80 (95% CI as 0.74-0.86, P<0.05) and 0.75(95% CI as 0.66-0.84, P<0.05), respectively. The C-index value of clinical-radiomics combined prediction model in the training dataset and the validation dataset was 0.88(95% CI as 0.85-0.92) and 0.83 (95% CI as 0.77-0.89), respectively. Results of calibration curve show that clinical prediction model, radiomics prediction model and clinical-radiomics combined prediction model had good predictive ability. Results of decision curve show that the clinical-radiomics combined prediction model is superior to the clinical prediction model, radiomics prediction model in evaluating the prognosis of patients with GNEN. Conclusions:The predection model for predicting the prognosis of patients with GNEN is constructed based on 14 radiomics features after selecting. The prediction model can predict the prognosis of patients with GNEN well, and the clinical-radiomics combined prediction model has a better prediction efficiency.

Clinical analysis of 17 cases of neonatal lupus erythematosus / 中国小儿急救医学

Objective:To summarize the clinical features of neonatal lupus erythematosus(NLE) and improve the understanding of the disease.Methods:The clinical data of 17 NLE neonates admitted to the First Affiliated Hospital of Zhengzhou University from February 2015 to September 2021 were retrospectively analyzed, and relevant literatures were reviewed.Results:Of the 17 patients, nine were boys and eight were girls.There were 13 cases of skin damage and eight cases of heart damage, including four cases of atrioventricular block, one case of QT interval prolongation complicated with atrial premature beat, three cases of atrial septal defect, one case of ventricular septal defect, two cases of patent ductus arteriosus, one case of pericardial effusion, one case of pulmonary hypertension, and two cases of cardiac insufficiency.One case developed skin damage and heart block at the same time.There were 15 patients with blood system damage and 11 patients with hepatobiliary system damage.Among the serological indicators, 17 cases were positive for anti-ANA antibody, 12 cases were positive for anti-SSA-60, 13 cases were positive for anti-SSA-52, seven cases were positive for SSB, one case was positive for Sm, and three cases were positive for RNP.Among them, four neonates with atrioventricular block were positive for anti-SSA-60 and anti-SSA-52.Most of the patients with skin lesions had good prognosis, and only one patient had brown scars, one neonate with second-degree type Ⅱ atrioventricular block and one neonate with QT interval prolongation combined with premature atrial contractions had normal electrocardiograms.Additionally, two patients still had third-degree atrioventricular block, and the other one patient was installed with a pacemaker at one year and two months, and left spastic cerebral palsy.A total of 16 mothers had serological tests, among which ten cases had abnormal connective tissue antibodies before delivery and six cases had abnormal connective tissue antibodies after delivery.Conclusion:There is no significant gender difference in NLE, third-degree atrioventricular block is difficult to reverse, and most patients with extracardiac damage have a good prognosis.

Clinical application of nutritional risk scale in pediatric cancer patients:a review / 中国实用护理杂志

The basic information and clinical application of nutritional risk scales for children with cancer were reviewed, and the strengths and weaknesses of each scale were analyzed. After systematic search and reading, the scales with more clinical applications included universal scales: Pediatric Malnutrition Assessment Screening Tool (STAMP), Nutritional Risk and Stunting Malnutrition Screening Tool (STRONG kids), Pediatric Yorkhill Malnutrition Score (PYMS), Pediatric Subjective Global Nutritional Risk Assessment (SGNA); specific scales: Nutritional Screening Tool for Childhood Cancer (SCAN), Nutritional Risk Screening for Childhood Cancer (NRS-PC). In order to effectively manage the nutritional risk of pediatric cancer patients, we should selectively use and further actively Chinese or develop specific nutritional risk measurement tools adapted to our national conditions.

Serum monocyte/high-density lipoprotein cholesterol ratio and urinary albumin/creatinine ratio in evaluating osteoporosis in diabetic nephropathy patients / 中华内分泌外科杂志

Objective:To investigate the value of serum monocyte/high-density lipoprotein cholesterol ratio (MHR) and urinary albumin/creatinine ratio (ACR) in the evaluation of osteoporosis in diabetic nephropathy patients.Methods:Diabetic nephropathy patients treated in Hangzhou Ninth People’s Hospital from Jun. 2019 to Jun. 2022 were selected. Gender, age, height and weight of all patients were collected and recorded, and body mass index (BMI) was calculated. Blood calcium (Ca), blood phosphorus (P), parathyroid hormone (PTH), monocyte count (M), high density lipoprotein (HDL-C), urinary microalbumin and creatinine were measured and recorded in all patients. MHR and ACR were calculated, MHR=M/HDL-C, ACR=urinary microalbumin/creatinine. Lumbar spine bone mineral density (L1-L4) was measured by dual-energy X-ray absorptiometry, which was divided into osteoporosis group and non-osteoporosis group.Results:Among the 117 diabetic nephropathy patients, 47 cases were osteoporotic and 70 cases were non-osteoporotic. The proportion of women in osteoporosis group was significantly higher than that in non-osteoporosis group, and BMI, PTH, MHR, ACR and bone mineral density were significantly higher than those in non-osteoporosis group, with statistical significance (all P<0.05). Multivariate binary Logistic regression analysis showed that female, MHR and ACR were independent risk factors for osteoporosis in diabetic nephropathy patients (all P<0.05). Spearman correlation analysis showed that serum MHR and ACR were negatively correlated with lumbar bone density, with statistical significance ( r=0.524 and 0.497, P=0.004 and 0.009, respectively). ROC curve analysis showed that the area under the curve (AUC) of serum MHR and ACR for evaluating osteoporosis in diabetic nephropathy patients was 0.870 (0.809-0.931) and 0.849 (0.792-0.905), respectively. The AUC of serum MHR combined with ACR for osteoporosis in diabetic nephropathy patients was 0.927 (0.891-0.964) . Conclusion:Serum MHR and ACR can be used as the evaluation indexes of osteoporosis in diabetic nephropathy patients, and their combined efficacy is better.

Application of scenario simulation teaching combined with modular training in nursing education of medical rescue in manned space flight / 中华急诊医学杂志

Objective:To study the application of scenario simulation teaching combined with modular training in nursing education of medical rescue in manned space flight.Methods:Twenty nurses from the medical rescue team of Strategic Support Force Characteristic Medical Center were selected as the research objects. The research objects were randomly divided into the scenario simulation combined with practical training group (practical training group, n=10) and traditional teaching group (control group, n=10). Scenario simulation teaching combined with modular training and traditional teaching were used to carry out nursing training. After the training, theoretical assessment, operation assessment and satisfaction survey were organized. Results:The scenario simulation teaching combined with modular training group was significantly better than the traditional training group in theory assessment, operation assessment and satisfaction survey of nursing staff (all P<0.05). Conclusions:Scenario simulation teaching combined with modular training has obvious teaching effect, which can improve the ability and quality of nursing staff, and help to complete the manned space medical rescue mission efficiently.

Construction and application of the module of medical first-aid at the door of the space capsule and the air evacuation after the manned spaceflight lands / 中华急诊医学杂志

Objective:To explore the module of the construction and application of medical first-aid at the door of the space capsule and the air evacuation.Methods:According to the purpose, principle, and method set by the module, it was divided into two sub-modules: medical first-aid at the door of the space capsule and the air evacuation. During the comprehensive first-aid training, independent training and combined training were carried out respectively according to different mission stages of launch and recovery and different recovery terrain. Meanwhile, research was performed to ensure that medical carrying equipment was lightweight, modular, and portable, and the efficiency of modularization construction was tested in the comprehensive training.Results:The module of medical first-aid at the door of the space capsule and the air evacuation obviously shortened the rescuing time during the comprehensive training, the saving effect was remarkable, and the overall saving efficiency was significantly improved.Conclusions:The module of medical first-aid at the door of the space capsule and the air evacuation meet the requirements that the emergency support system of aerospace medicine should function on an immediate basis, ensuring accurate treatment and air evacuation without any delay, so that to achieve the aim of aerospace medicare.

Research progress in the influence of needling different acupoints on heart rate variability and the mechanism of autonomic nerve regulation / 国际中医中药杂志

By summarizing and analyzing the research status of the influence of needling different acupoints on heart rate variability (HRV) and autonomic nervous function, it is found that Neiguan (PC 6), Zusanli (ST 36) and Shenmen (HT 7) are common acupoints for HRV analysis involving Tongli (HT 5), Hegu (LI 4), Taichong (LR 3), Zhongwan (RN 12), Danzhong (RN 17), Xinshu (BL 15), Shenshu (BL 23) and other acupoints. Different acupoints have different influences on HRV but followed by some rules, which are possibly related to the efficacy of acupoints, meridian tropism and acupoint distributions. Needling on the same acupoint also has different influences on HRV, which is possibly affected by sample size, intervention object, data processing method and other factors, so more standardized measurement process is required in further studies.

To explore the application status and prospect of sham acupuncture in clinical trials of acupuncture based on 5G+VR technology / 国际中医中药杂志

Acupuncture has been proved to be safe and effective by large-scale and authoritative clinical observation at home and abroad. However, in recent years, the results of some randomized controlled trials of acupuncture in JAMA showed no significant difference between acupuncture effect and sham acupuncture effect. Acupuncture and moxibustion in clinical practice is a summary of academic and clinical rules. Different from chemical drugs, the amount of stimulation, methods of operation and techniques vary. At present, sham acupuncture in clinical trials at home and abroad has been questioned by many scholars, who believe that sham acupuncture is not fake, and call for "fake targeted research" to be stopped. In order to improve the sham acupuncture control design, 5G + VR technology and the principle elements of sham acupuncture should be combined. We also discussed and analyzed advantages and prospects of modern intelligent medical technology of 5G + VR technology in the sham acupuncture RCT. We hope to promote standardization of acupuncture clinical trials, and the development, innovation and application of acupuncture research at home and abroad.

Research progress of 4-nitroquinoline-1-oxide-induced esophageal squamous cell carcinoma model in mice / 国际肿瘤学杂志

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a poor prognosis. 4-nitroquinoline-1-oxide (4NQO) is a water-soluble quinoline derivative that can successfully induce the production of squamous cell carcinoma in vivo. Establishing and optimizing experimental methods for 4NQO induced ESCC formation in mice can provide a more suitable in situ model for the study of ESCC.

Advances in the fluid management strategies of pediatric acute respiratory distress syndrome / 国际儿科学杂志

Pediatric acute respiratory distress syndrome(PARDS)is a pulmonary inflammation syndrome caused by a variety of proinflammatory factors induced by many causes, which is mainly characterized by noncardiogenic pulmonary edema.The main pathophysiological feature is the destruction of the integrity of the alveolar capillary membrane, and the loss of the alveolar epithelial-endothelial barrier function.In the PARDS′s clinical practice, the mainstay of the treatment is supportive.Although there is still no clear definition and general consensus or guidelines, appropriate liquid therapy is an important part of non-ventilatory treatment measures.Proper fluid management strategy is helpful to improve pulmonary edema, maintain normal circulatory perfusion, prevent functional failure of important organs and improve the prognosis of patients.According to volume status, implementing the goal-oriented and phased differentiated fluid management strategy is significant for the therapy of PARDS patients.However, the effects of fluid strategy management according to PARDS phenotypes remain to be evaluated.

Progress in the pathogenesis of eosinophilic gastrointestinal diseases / 国际儿科学杂志

Eosinophilic gastrointestinal diseases are a group of diseases with repeated or persistent gastrointestinal symptoms and the increase of eosinophils in gastrointestinal mucosa.Pathology shows an increase in the number of eosinophils in gastrointestinal mucosa.Fibrosis can be seen in the lamina propria of esophageal mucosa in patients with eosinophilic esophagitis.A variety of cytokines may be chemotactic to the aggregation of eosinophils, including Th2 cytokines, eotaxin, thymic stromal lymphopoietin, macrophage migration inhibitory factor, sialic acid-binding immunoglobulin-like lectin, integrin and extracellular matrix protein.The intestinal tissue injury of eosinophilic gastrointestinal diseases may be related to eosinophil degranulation and secretion of specific products, inflammatory response, oxidative damage, fibrosis, tissue remodeling and impaired barrier function.

Application and prospect of artificial intelligence in antimicrobial peptides screening / 中国药科大学学报

@#Antimicrobial peptides (AMPs) are a class of small molecule peptides with broad-spectrum antimicrobial activity.Their unique antimicrobial mechanism can effectively treat infectious diseases, with rare drug resistance.However, though AMPs with antimicrobial activity can be screened by traditional methods, the whole process is complicated.The artificial intelligence (AI) screening method is faster and more convenient, with great potential in exploring new natural antimicrobial peptides.In this paper, strategies related to AMPs screening by AI were summarized and compared, including data sources applied to model training, artificial intelligence machine model and omics data applied to model screening of novel antimicrobial peptides.The application prospects and advantages were reviewed, in hope of providing new ideas for identification, research and development of antimicrobial peptides.

FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.

Acetylcorynoline inhibits microglia activation by regulating EGFR/MAPK signaling to promote functional recovery of injured mouse spinal cord / 南方医科大学学报

OBJECTIVE@#To investigate the effect of acetylcorynoline (Ace) for promoting functional recovery of injured spinal cord in rats and explore the underlying mechanism.@*METHODS@#Rat models of spinal cord injury (SCI) were treated with intraperitoneal injection of different concentrations of Ace, with the sham-operated rats as the control group. After the treatment, the changes in motor function of the rats and the area of spinal cord injury were assessed with BBB score and HE staining, and the changes in pro-inflammatory cytokine levels and microglial activation were determined using PCR, ELISA and immunofluorescence staining. In a lipopolysaccharide (LPS)-treated BV2 cell model, the effects of different concentrations of Ace or DMSO on microglial activation and inflammatory cytokine production were observed. Network pharmacology analysis was performed to predict the target protein and signaling mechanism that mediated the inhibitory effect of Ace on microglia activation, and AutoDock software was used for molecular docking between Ace and the target protein. A signaling pathway blocker (Osimertinib) was used to verify the signaling mechanism in rat models of SCI and LPS-treated BV2 cell model.@*RESULTS@#In rat models of SCI, Ace treatment significantly increased the BBB score, reduced the area of spinal cord injury, and lowered the number of activated microglia cells and the levels of pro-inflammatory cytokines (P < 0.05). The cell experiments showed that Ace treatment significantly lower the level of cell activation and the production of inflammatory cytokines in LPS-treated BV2 cells (P < 0.05). Network pharmacology analysis suggested that EGFR was the main target of Ace, and they bound to each other via hydrogen bonds as shown by molecular docking. Western blotting confirmed that Ace inhibited the activation of the EGFR/MAPK signaling pathway in injured mouse spinal cord tissue and in LPS-treated BV2 cells, and its inhibitory effect was comparable to that of Osimertinib.@*CONCLUSION@#In rat models of SCI, treatment with Ace can inhibit microglia-mediated inflammatory response by regulating the EGFR/MAPK pathway, thus promoting tissue repair and motor function recovery.

Enhanced endoplasmic reticulum RyR1 receptor phosphorylation leads to diaphragmatic dysfunction in septic rats / 南方医科大学学报

OBJECTIVE@#To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction.@*METHODS@#Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting.@*RESULTS@#In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05).@*CONCLUSION@#Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.