Study on spleen strengthening effects and mechanisms of Atractylodes chinensis and Atractylodes coreana / 中国药理学通报

Aim To analyze the differences in plasma biomarkers and metabolic pathways between Atractylodes chinensis and Atractylodes coreana after intervention in spleen deficiency rats, and discuss the spleen strengthening mechanism of the two from a non targeted metabolomics perspective. Methods A spleen deficiency model was established in SD rats using a composite factor method of improper diet, excessive fatigue, and bitter cold diarrhea. To determine the content of gastrointestinal and immunological indicators, UHPLC-QE-MS technology was used, combined with principal component analysis (PC A) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) methods to search for biomarkers in plasma of spleen deficiency rats, and metabolic pathways were induced using the Pathway database. Results After administration of Atractylodes chinensis and Atractylodes coreana, various indicators in plasma of spleen deficiency rats showed varying degrees of regression. Metabolomics analysis showed that Atractylodes chinensis and Atractylodes coreana respectively recalled 70 and 82 plasma differential metabolites. Atractylodes chinensis mainly regulated two metabolic pathways : "Glycine, serine, and threonine metabolism, and "Thiamine metabolism". Atractylodes coreana mainly regulated five metabolic pathways, "Glycine, serine, and threonine metabolism", "Thiamine metabolism, "Pyrimidine metabolism", "Butanoate metabolism", and "Riboflavin metabolism". Conclusions Both Atractylodes chinensis and Atractylodes coreana have certain regulatory effects on spleen deficiency rats, and their mechanism of action may be related to regulating metabolic pathways such as "Glycine, serine, and threonine metabolism, and "Thiamine metabolism"in spleen deficiency.

Oncologic outcomes of surgical treatments of advanced sinonasal malignancies / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the prognoses of advanced (T3-T4) sinonasal malignancies (SNM). Methods: The clinical data of 229 patients with advanced (T3-4) SNM who underwent surgical treatments in the First Affiliated Hospital of Sun Yat-sen University from 2000 to 2018 were retrospectively analyzed, including 162 males and 67 females, aged (46.8±18.5) years old. Among them, 167 cases received endoscopic surgery alone, 30 cases received assisted incision endoscopic surgery, and 32 cases received open surgery. The Kaplan-Meier method was used to estimate the 3-year and 5-year overall survival (OS) and event-free survival (EFS). Univariate and multivariate Cox regression analyses were performed to explore significant prognostic factors. Results: The 3-year and 5-year OS were respectively 69.7% and 64.0%. The median OS time was 43 months. The 3-year and 5-year EFS were respectively 57.8% and 47.4%. The median EFS time was 34 months. The 5-year OS of the patients with epithelial-derived tumors was better than that of the patients with mesenchymal-derived tumors and malignant melanoma (5-year OS was respectively 72.3%, 47.8% and 30.0%, χ2=36.01, P<0.001). Patients with microscopically margin-negative resection (R0 resection) had the best prognosis, followed by macroscopically margin-negative resection (R1 resection), and debulking surgery was the worst (5-year OS was respectively 78.4%, 55.1% and 37.4%, χ2=24.63, P<0.001). There was no significant difference in 5-year OS between the endoscopic surgery group and the open surgery group (65.8% vs. 53.4%, χ2=2.66, P=0.102). Older patients had worse OS (HR=1.02, P=0.011) and EFS (HR=1.01, P=0.027). Patients receiving adjuvant therapy had a lower risk of death (HR=0.62, P=0.038). Patients with a history of nasal radiotherapy had a higher risk of recurrence (HR=2.48, P=0.002) and a higher risk of death (HR=2.03, P=0.020). Conclusion: For patients with advanced SNM, the efficacy of endoscopic surgery can be comparable to that of open surgery when presence of safe surgical margins, and a treatment plan based on transnasal endoscopic surgery as the main comprehensive treatment is recommended.

Impact of statin use on major adverse cardiovascular events in patients with normal stress myocardial perfusion imaging and elevated coronary artery calcium score

INTRODUCTION@#Normal stress myocardial perfusion imaging (MPI) carries a favourable prognosis. Conversely, elevated coronary artery calcium (CAC) is associated with increased major adverse cardiovascular events (MACE). There is limited information on the prognosis and management of patients with elevated CAC and normal MPI. We aimed to assess the outcomes of patients with elevated CAC and normal MPI in relation to post-MPI statin use.@*METHODS@#A retrospective review of normal MPI with CAC score >300 was performed between 1 March 2016 and 31 January 2017 in a Singapore tertiary hospital. Patients with known atherosclerotic cardiovascular disease or left ventricular ejection fraction <50% on MPI were excluded. Patient demographics, prescriptions and MACE (cardiac death, nonfatal myocardial infarction and/or ischaemic stroke) at 24 months after MPI were traced using electronic records. Binary logistic regression was used to evaluate for independent predictors of MACE.@*RESULTS@#We included 311 patients (median age 71 years, 56.3% male), of whom 65.0% were on moderate to high-intensity statins (MHIS) after MPI. MACE was significantly lower in the post-MPI MHIS group (3.5% vs. 9.2%, P = 0.035). On univariate binary logistic regression, post-MPI MHIS use was the only significant predictor for MACE (odds ratio [OR] 0.355 [95% confidence interval (CI) 0.131-0.962], P = 0.042), even after multivariate adjustment (adjusted OR 0.363, 95% confidence interval 0.134-0.984, P = 0.046).@*CONCLUSION@#Post-MPI MHIS use is associated with lower MACE and is an independent negative predictor for 24-month MACE among patients with normal MPI and CAC >300.

Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury: A Multicenter Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI).@*METHODS@#This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia.@*RESULTS@#The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group.@*CONCLUSION@#Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).

The preliminary study of extracorporeal carbon dioxide removal in acute respiratory distress syndrome for a pediatric patient / 中国小儿急救医学

Objective:Extracorporeal carbon dioxide removal(ECCO 2R) is a technique that aims to decarboxylate the blood and thus to correct hypercapnia and respiratory acidosis in acute respiratory failure, but is rarely used in children.We successfully completed the ECCO 2R treatment for a pediatric case with adenovirus pneumonia, severe acute respiratory distress syndrome(ARDS) and hypercapnia in PICU, which provided clinical references for the use of ECCO 2R in acute respiratory failure for children. Methods:A patient with adenovirus pneumonia and severe ARDS was successfully treated with ECCO 2R-continuous renal replacement therapy(CRRT)combined system after weaning from extracorporeal membrane oxygenation(ECMO). We reported the treatment process, ECCO 2R treatment effect and side effects, so as to provide clinical reference for ECCO 2R treatment of children with ARDS. Results:One-year and four-month-old boy was treated with mechanical ventilation and venous-arterial ECMO due to adenovirus pneumonia and severe ARDS.After ECMO treatment for 25 days, he developed severe hypercapnia after weaning from ECMO.ECCO 2R was initiated.The pH value increased by 11.2%(from 7.222 to 7.303) 1 hour after ECCO 2R treatment, partial pressure of blood carbon dioxide(PCO 2)decreased by 29.1%(from 72.6 mmHg to 51.5 mmHg, 1 mmHg=0.133 kPa) and the average airway pressure of high-frequency ventilation decreased by 5 cmH 2O(from 20 cmH 2O to 15 cmH 2O, 1 cmH 2O=0.098 kPa) after 6 hours of ECCO 2R.The CO 2 removal rate of ECCO 2R system was 29.1 mL/min.It was stopped because of ECCO 2R-membrane clotting after 72 h. There was no increase of PCO 2.Extubation was successfully after undergoing invasive mechanical ventilation for 39 days and with noninvasive ventilation for 5 days.The boy was hospitalized in PICU for 54 days, improved and discharged from the hospital.Followed up for 2 years after discharge, the growth and development were good, but the strenuous exercise endurance was still poor. Conclusion:ECCO 2R is effective in improving gas exchange, reducing PCO 2 and lowering ventilator pressure in children with ARDS and hypercapnia, which allow more protective ventilation.ECCO 2R provide transitional treatment for ECMO weaning and provide meaningful clinical reference for the use of ECCO 2R as part of respiratory support in children with respiratory failure.

Research progress in drugs targeting tumor associated macrophage / 药学学报

Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.

Advances of SHP2 modulators in the cancer immunotherapy / 药学学报

Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke

Background@#and Purpose The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). @*Methods@#We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. @*Results@#IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237–0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity.However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. @*Conclusions@#Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

Progress on targets and therapeutic drugs for pancreatic cancer / 药学学报

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Mental Health Status and Influencing Factors of Pediatricians in Guangzhou / 中山大学学报(医学科学版)

ObjectiveTo investigate the mental health of pediatricians in Guangzhou and its influencing factors， and to provide countermeasures for improving the mental health of pediatricians. MethodsA stratified random sampling method was used to randomly select 400 pediatricians in 11 districts of Guangzhou， and they were surveyed using the Symptom Check List（SCL-90） and the Job Stressor Scale. ResultsThe top three job stressors scored by pediatricians in Guangzhou were external environment （3.23±0.59）， workload （3.19±0.56）， and organizational management （2.74±0.55）. All factor scores were higher than those of the clinician group except for career interest， and the difference was statistically significant （P<0.01）. The number of pediatricians with mental health problems was 109， accounting for 27.25%. All factor scores were higher than the physician norm except for anxiety and paranoia. The correlations between each factor of work stressors and each factor of SCL-90 were positive and statistically significant （P<0.05）， except for two pairs of factors， workload and terror as well as external environment and terror. The results of univariate analysis showed statistically significant differences in the mental health scores of pediatricians with different health status， years of work experience， job satisfaction， job stress， and career prospects （P<0.05）. The results of multiple linear regression showed that health status， years of work experience， professional interest， interpersonal relationship， and doctor-patient relationship were influential factors in the mental health of pediatricians （P<0.05）. ConclusionThe mental health of pediatricians in Guangzhou is unsatisfactory， and the factors affecting them are mainly external objective factors such as workload and organizational management.

CiteSpace knowledge map of gut microbiota research involving traditional Chinese medicine in recent twenty years / 中国中药杂志

We employed bibliometrics to comprehensively study the hotspots and frontiers of gut microbiota research involving traditional Chinese medicine(TCM), aiming to provide new ideas for the subsequent research in this field. The studies of gut microbiota with TCM published from January 1, 2002 to December 31, 2021 were retrieved from CNKI, Wanfang, VIP and Web of Science(WoS). After data screening and cleaning, CiteSpace 5.8.R3 was used to visualize and analyze the authors, journals, and keywords. A total of 1 119 Chinese articles and 815 English articles were included in the study. The period of 2019-2021 witnessed the surge in the number of articles published in this field, being the peak research period. TAN Zhou-jin and DUAN Jin-ao were the authors publishing the most articles in Chinese and English, respectively. The two authors ranked top in both Chinese and English articles, playing a central role in this research field. The top five Chinese and English journals in this field had a large influence in the international research field. High-frequency keywords and keyword clustering showed that the research hotspots in this field were concentrated in four areas: trial and clinical research on the regulation of gut microbiota in disease treatment by TCM, metabolic transformation of Chinese medicines by gut microbiota, and the effect of TCM added to feed on the gut microbiota and growth performance of animals. The study of gut microbiota structure in patients with different TCM syndromes, as well as that of TCM combined with probiotics/flora transplantation in the treatment of diseases, can provide new ideas for clinical diagnosis and traditional drug treatment of diseases and has great research space and research value in the future.

Short-term efficacy of dapagliflozin in children with hereditary proteinuric kidney disease / 中华儿科杂志

Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m2, P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m2), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.

Association between cardiometabolic diseases and quality of life and the mediation effect of perceived stress / 中华心血管病杂志

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a2b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.

β-Catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice / 神经科学通报·英文版

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.

MicroRNA Mediates Post-transcriptional Regulation of Macrophage Polarization / 中国生物化学与分子生物学报

Macrophage polarization is a process of phenotypic regulation based on the surroundingstimulus environment, which is generally polarized into two phenotypes, namely classical activated M1macrophages and alternative activated M2 macrophages. In short, M1 macrophages are characterized aspro-inflammatory and anti-tumor; M2 macrophages are anti-inflammatory and pro-tumor. Macrophagepolarization is considered to be a key regulator of human physiology and pathology processes, and itseffectiveness depends on the coordinated expression of key factors, whose expression is finely regulated bymicroRNAs (miRNAs) at the post-transcriptional level. MicroRNAs are small non-coding RNAs that havethe ability to regulate gene expression and cellular network processes. More and more evidence shows thatmiRNAs play an important role in regulating macrophage polarization. Therefore, in this review, miRNAsregulating macrophage polarization to M1 / M2 type and have bidirectional regulation function are listed, and how they regulate macrophage polarization through transcription factors and their potential in thetreatment of inflammation and tumor.

Mechanism of Mahuang-Dahuang herb pair inhibiting M1 polarization of alveolar macrophages in prevention and treatment of acute lung injury / 中国药理学通报

Aim To investigate the effect of Mahuang-Dahuang(MD)on inhibiting M1 polarization of alveolar macrophages, alleviating inflammatory injury and treating acute lung injury, and the underlying mechanism.Methods Abandoned rats were divided into normal control group(NC), model control group(MC), MD high-dose group(MD-H), medium-dose group(MD-M), low-dose group(MD-L), and DXMS group.Lipopolysaccharide(LPS)was injected intraperitoneally to prepare an acute lung injury(ALI)rat model.After the model was established, different doses of MD were administered by intragastric administration, and the pathological changes of lung tissues were observed; immunohistochemical method was used to detect the expression of alveolar macrophage marker F4/80,F4/80 and CD80, CD80 and IL-6 Co-expression; Flow cytometry was used to detect the content of F4/80 and CD80 in lung tissues; PCR was used to detect the relative expression of IL-6, INOS, TNF-α mRNA in lung tissues; Western blot was used to detect lung tissue CCR2, CCL2, p-p65, P65, p-p38MAPK, p38MAPK protein expression.Results Compared with NC group, rats in MC group had damaged alveolar structure, thickened pulmonary interstitial edema, and infiltrated a large number of inflammatory cells.Among them, the number of macrophages increased significantly, which promoted the increase in the expression of macrophages-related chemokines CCR2 and CCL2.The number and expression of M1 alveolar macrophages in lung tissues increased, the relative expression of M1 alveolar macrophages-related cytokines IL-6, INOS and TNF-α mRNA was up-regulated, and the target protein in the related pathways of alveolar macrophages M1 polarization p-NF-κBp65/NF-κBp65, p-P38MAPK/p38MAPK protein expression was up-regulated.Compared with MC group, the pathological status of lung tissues in MD high, medium, and low dose groups was significantly improved, the number of lung tissue M1 alveolar macrophages decreased, the relative expression of inflammatory factors IL-6, INOS and TNF-α mRNA was down-regulated, and the protein expression of CCR2, CCL2, p-NF-κBp65/ NF-κBp65 and p-P38MAPK/p38MAPK was reduced in lung tissues.Conclusions MD can inhibit the M1 polarization of alveolar macrophages, reduce the activation and release of inflammatory factors, inhibit inflammatory response, and prevent acute lung injury by regulating the expression of related indicators of NF-κB and MAPK signaling pathways.

Combined Therapy of Lung and Intestine in Treatment of Lung Diseases： A Review / 中国实验方剂学杂志

The theoretical origin of the combined therapy of lung and intestine can be traced back to the Inner Canon of Huangdi （《黄帝内经》）， which explains the physiological and pathological interaction between the lung and the large intestine. In recent years， researchers have investigated the scientific essence of the "lung-intestine axis" theory from many aspects， which enriches the relevant theoretical basis， and applied it to the treatment of COVID-19， acute lung injury， and other lung diseases. The close relation between lung and intestine in many aspects embodies the holistic conception of traditional Chinese medicine and explains the holistic theory of interrelation between organs， which correlate to each other physiologically and pathologically. Intestinal microecological disorders can affect lung immune function and cause respiratory diseases， and respiratory diseases are usually accompanied by gastrointestinal symptoms. Lung diseases can be prevented and treated by regulating intestinal flora. According to histoembryology， the epithelial tissue of the lung and intestine comes from primitive foregut. In immunology， both lung and intestine contain mucosa-associated lymphoid tissue， and the pathological changes of the respiratory tract are also closely related to intestinal microorganisms. The tissue origin of lung and large intestine， the correlation of mucosal immunity， and the synchronization of ecological changes provide a scientific basis for the combined therapy of lung and intestine. Therefore， this paper summarizes the theoretical origin， modern research mechanism， and clinical application of combined therapy of lung and intestine， in order to provide a new direction for its application in clinical and scientific research.

Effect of Combined Therapy of Lung and Intestine on VIP and p38 MAPK Signaling Pathways in Bronchial Asthma Mice / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effects of the combined therapy of lung and intestine， a common treatment for pulmonary diseases in traditional Chinese medicine （TCM）， on bronchial asthma mice， and further detect the changes of vasoactive intestinal peptide （VIP） and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway-related proteins which are closely related to the pathogenesis of asthma， in order to elucidate the mechanism of the combined therapy of lung and intestine in the treatment of bronchial asthma. MethodA total of 60 Kunming mice were randomly divided into normal group， model group， dexamethasone group （0.5 mg·kg-1·d-1）， TCM group （2.73 g·kg-1·d-1）， and lung-intestine treatment group （6.825 g·kg-1·d-1）， 12 mice in each group. All mice except the normal group were sensitized by ovalbumin to induce bronchial asthma. After 30 days of intragastric administration， serum and lung tissue samples were obtained. The content of VIP， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum of mice in each group was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of TNF-α， IL-6， and p38 MAPK in lung tissues of mice were detected by real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of TNF-α， IL-6， p38 MAPK， and phosphorylated p38 MAPK （p-p38 MAPK） in lung tissues of mice were assayed by Western blot （WB）. ResultCompared with the normal group， the model group showed decreased content of serum VIP （P<0.05）， increased content of TNF-α and IL-6 （P<0.05）， up-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and elevated protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. Compared with the model group， the treatment groups exhibited increased content of serum VIP， TNF-α， and IL-6 （P<0.05）， down-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and lower protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. As compared with the lung-intestine treatment group， the serum TNF-α and IL-6 levels in the dexamethasone group were increased （P<0.05）， and the mRNA and protein levels of TNF-α and IL-6 in lung tissues were down-regulated （P<0.05）， while the levels of p38 MAPK， VIP mRNA， and p-p38 MAPK/p38 MAPK protein in lung tissues were up-regulated （P<0.05）. The serum VIP， TNF-α， and IL-6 levels in the TCM group were decreased （P<0.05）， and the mRNA levels of TNF-α， IL-6， p38 MAPK and protein levels of TNF-α， IL-6， p-p38 MAPK/p38 MAPK in lung tissues were up-regulated （P<0.05）， while the level of VIP mRNA in lung tissues was down-regulated （P<0.05）. ConclusionThrough increasing endogenous VIP and inhibiting the excessive activation of p38 MAPK signaling pathway， the combined therapy of lung and intestine can reduce the release of inflammatory factors， inhibit pulmonary inflammation response， and treat bronchial asthma.

Mechanism of Combined Therapy of Lung and Intestine in Alleviating Pulmonary Edema in Treatment of Acute Lung Injury Based on VIP/cAMP/PKA/AQPs Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of the combined therapy of lung and intestine （Mahuangtang + Da Chengqitang） in alleviating pulmonary edema in rats with acute lung injury （ALI） induced by lipopolysaccharide （LPS）. MethodWistar rats were randomly divided into blank group， model group， low-， medium-， and high-dose groups with combined therapy of lung and intestine， and positive control group. LPS （10 mg·kg-1） was given （ip） to induce ALI in rats. After modeling， the blank group was given normal saline （25 mL·kg-1）， the combined therapy of lung and intestine treatment groups were given （ig） low- （5 g·kg-1）， medium- （7.5 g·kg-1）， and high-dose （10 g·kg-1） Mahuangtang and Da Chengqitang， and the positive control group was given dexamethasone （5 mg·kg-1）. Medications were administered 0， 8， and 16 h after LPS injection for 3 times. Then lung tissue and serum were collected after administration. The lung tissues were stained with haematoxylin-eosin （HE）， and the pulmonary edema score was evaluated. The dry/wet （D/W） weight ratio of lung tissues in each group was measured， and the content of serum vasoactive intestinal peptide （VIP） in rats was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein levels of aquaporin-1 （AQP1）， AQP5， VIP， cyclic adenosine monophosphate （cAMP）， phosphorylated protein kinase A （p-PKA）， and PKA in lung tissues of rats in each group. The level of VIP mRNA in lung tissues of rats was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group exhibited obvious lung injury， increased edema score， decreased D/W ratio （P<0.01）， declined AQP1， AQP5， cAMP， and p-PKA/PKA in lung tissues （P<0.05， P<0.01）， elevated VIP content （P<0.01）， and up-regulated levels of VIP protein and mRNA in lung tissues （P<0.05， P<0.01）. Compared with the model group， combined therapy of lung and intestine treatment groups showed alleviated lung injury， increased D/W ratio （P<0.01）， elevated AQP1， AQP5， VIP， cAMP， and p-PKA/PKA in lung tissues （P<0.05， P<0.01）， and up-regulated VIP levels in lung tissues （P<0.05， P<0.01）. ConclusionThe combined therapy of lung and intestine can alleviate ALI-induced lung tissue edema， and the mechanism may be related to the activation of the VIP/cAMP/PKA signaling pathway， which further promotes the expression of AQP1 and AQP5 and enhances the water metabolism of lung tissue.

Effect of Combined Therapy of Lung and Intestine on NF-κB Inflammatory Pathway and Macrophage Polarization in LPS-induced Acute Lung Injury Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of combined therapy of lung and intestine （Mahuangtang + Da Chengqitang） on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in rats and its protective mechanism. MethodWistar rats were randomly divided into blank group， model group， low-， medium-， and high-dose groups with combined therapy of lung and intestine ， and dexamethasone group. LPS （10 mg·kg-1） was given （ip） to induce ALI in rats. The general state of rats in each group was observed and recorded. The body temperature of rats in each group was recorded 0-8 h after modeling by means of anal temperature measurement. Serum and lung tissues were collected 24 h after modeling. Serum levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and arginase-1 （Arg-1） were determined by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein levels of nuclear factor kappa B p65 （NF-κB p65）， phosphorylated NF-κB p65 （p-NF-κB p65）， NF-κB inhibitor α （IκBα）， and phosphorylated IκBα （p-IκBα） in lung tissues of rats. The levels of classically activated （M1） macrophage marker CD80 and IL-1β and macrophage markers F4/80 and IL-10 were detected by double immunofluorescence. ResultCompared with the blank group， the model group showed increased body temperature and thermal response index （TRI）， elevated serum levels of pro-inflammatory factor TNF-α and IL-1β and anti-inflammatory factor IL-10 （P<0.01）， up-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.01）， and increased levels of F4/80， CD80， and IL-1β in lung tissues （P<0.01）. Compared with the model group， the lung-intestine combined treatment groups and the dexamethasone group exhibited decreased body temperature and TRI in rats （P<0.01）， declined serum levels of inflammatory factor TNF-α and IL-1β （P<0.05， P<0.01）， elevated serum levels of anti-inflammatory factor IL-10 and Arg-1 （P<0.05， P<0.01）， down-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.05， P<0.01）， decreased levels of CD80 and IL-1β， and increased levels of IL-10 in lung tissues （P<0.01）， while the level of F4/80 was not significantly changed. ConclusionThe combined therapy of lung and intestine can obviously alleviate the fever and inflammatory state of ALI rats， and the mechanism may be related to the inhibition of NF-κB inflammatory pathway and the polarization of lung tissue macrophages to anti-inflammatory phenotype.