Ophiopogonin D attenuates doxorubicin-induced autophagic cell death by relieving mitochondrial damage in vitro and in vivo.

It has been reported that ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from Ophiopogon japonicas, promotes antioxidative protection of the cardiovascular system. However, it is unknown whether OP-D exerts protective effects against doxorubicin (DOX)-induced autophagic cardiomyocyte injury. Here, we demonstrate that DOX induced excessive autophagy through the generation of reactive oxygen species (ROS) in H9c2 cells and in mouse hearts, which was indicated by a significant increase in the number of autophagic vacuoles, LC3-II/LC3-I ratio, and upregulation of the expression of GFP-LC3. Pretreatment with OP-D partially attenuated the above phenomena, similar to the effects of treatment with 3-methyladenine. In addition, OP-D treatment significantly relieved the disruption of the mitochondrial membrane potential by antioxidative effects through downregulating the expression of both phosphorylated c-Jun N-terminal kinase and extracellular signal-regulated kinase. The ability of OP-D to reduce the generation of ROS due to mitochondrial damage and, consequently, to inhibit autophagic activity partially accounts for its protective effects in the hearts against DOX-induced toxicity.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Progress in immunotherapy for neuroendocrine neoplasm of the digestive system.

Neuroendocrine neoplasms (NENs) are rare heterogeneous tumors that can develop in almost any organ, with the digestive organs, including the gastrointestinal tract and pancreas being the most commonly affected sites. Despite the fact that advances in initial therapies have progressed, there is presently no recognized effective treatment for advanced NEN. Immune checkpoint inhibitors (ICIs) have shown superior efficacy in treating several types of solid tumors. Despite their successful role in the treatment of partial NENs, such as small cell lung cancer, and Merkel cell carcinoma, the role of ICIs in most of the NENs remains limited. Nevertheless, due to their specific anti-tumor mechanisms and acceptable safety profile, ICIs are a promising avenue for further study in NENs therapy. Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy, and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies. Therefore, the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system, with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor. Furthermore, this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.

Electrocardiogram-based artificial intelligence for the diagnosis of heart failure: a systematic review and meta-analysis.

BACKGROUND: The electrocardiogram (ECG) is an inexpensive and easily accessible investigation for the diagnosis of cardiovascular diseases including heart failure (HF). The application of artificial intelligence (AI) has contributed to clinical practice in terms of aiding diagnosis, prognosis, risk stratification and guiding clinical management. The aim of this study is to systematically review and perform a meta-analysis of published studies on the application of AI for HF detection based on the ECG. METHODS: We searched Embase, PubMed and Web of Science databases to identify literature using AI for HF detection based on ECG data. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria. Random-effects models were used for calculating the effect estimates and hierarchical receiver operating characteristic curves were plotted. Subgroup analysis was performed. Heterogeneity and the risk of bias were also assessed. RESULTS: A total of 11 studies including 104,737 subjects were included. The area under the curve for HF diagnosis was 0.986, with a corresponding pooled sensitivity of 0.95 (95% CI: 0.86-0.98), specificity of 0.98 (95% CI: 0.95-0.99) and diagnostic odds ratio of 831.51 (95% CI: 127.85-5407.74). In the patient selection domain of QUADAS-2, eight studies were designated as high risk. CONCLUSIONS: According to the available evidence, the incorporation of AI can aid the diagnosis of HF. However, there is heterogeneity among machine learning algorithms and improvements are required in terms of quality and study design.

Reward Design for Customer Referral Programs: Reward-Product Congruence Effect and Gender Difference.

Referral reward design is the core component of customer referral programs, which are often applied to recruit new customers. This research investigates the effectiveness of utilitarian vs. hedonic rewards in terms of referral generation. Through one field study and two laboratory studies, we demonstrate a reward-product congruency effect; that is, utilitarian rewards, compared with hedonic rewards, yield a higher referral likelihood for utilitarian products, while the opposite holds true for hedonic products. However, such a congruency effect would be crippled by gender segmentation. When males make referral decisions toward hedonic products, the effectiveness of utilitarian rewards is at least equal to that of hedonic rewards. When females make referral decisions toward utilitarian products, there is no difference in effectiveness between utilitarian and hedonic rewards. These findings provide novel insights into referral reward design.

YiQi YangYin Decoction Attenuates Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Rats.

BACKGROUND: YiQi YangYin Decoction (YQ) is a modern Chinese formula composed by the guidance of traditional Chinese medicine theory, which consists of nine traditional Chinese medicines and is applied to treat type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver in clinic in China for more than a decade. This study aims to evaluate the antidiabetes and lipid-lowering effect of YQ and explore the possible mechanisms of this action. METHODS: T2DM rat models were established and given YQ at three different doses for three weeks. Tissues, including pancreas islet and liver, and blood serum were collected. The levels of fasting blood glucose (FBG), fasting insulin (Fins), lipid index, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), and hepatic function index such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum were measured. Pancreas islet damage and liver damage were observed by hematoxylin and eosin staining. The glycogen content and lipid accumulation in liver were determined by periodic acid-Schiff (PAS) staining and Oil Red O staining. The expression levels of insulin receptor substrate 2 (IRS-2), phosphatidylinositol 3 kinase-associated p85alpha (PI3K p85α), AKT, and Glucose Transporter 2 (Glut4) in pancreas islet and AMP-activated protein kinase alpha (AMPKα), sterol regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase (ACC1), and peroxisome proliferator-activated receptor-α (PPARα) in liver were determined by western blotting. The relative expressions of ACC1, fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), carnitine palmityl transferase-1 (CPT-1), and SREBP-1 mRNA were detected by qRT-PCR. RESULTS: After administering YiQi for three weeks, the levels of fast blood glucose, fasting insulin, TC, TG, LDL, ALT, AST, and ALP were significantly decreased, while HDL significantly increased compared with the model group. YQ could obviously attenuate pancreatic damage and improve islet α- and ß-cell survival compared with the model group. Furthermore, YQ could attenuate hepatic damage caused by lipid accumulation, decrease the content of lipid, and increase the hepatic glycogen content, compared with the model group. In addition, YQ remarkably elevated the proteins expression of p-PI3K, p-AKT, and GLUT4 in pancreas islet and elevated the proteins expression of p-PI3K, p-AKT, GLUT4, p-AMPK, SREBP1, and PPARα and inhibited the expression of p-ACC1 in liver. Besides, YQ reduced the relative expression of ACC1, FAS, SERBP-1c, and SCD mRNA along with the decreased production of CPT-1 mRNA. CONCLUSIONS: YQ could attenuate type 2 diabetes mellitus by improving islet α- and ß-cells via IRS-2/AKT/GLUT4 pathway and nonalcoholic fatty liver by ameliorating lipid accumulation via AMPK/PPARα/SREBP1/ACC1 pathway.

A case report of congenital dysplasia caused by the ANK3 gene mutation in the newborn / 中华实用儿科临床杂志

The clinical features, examination findings and gene results of the newborn diagnosed with congenital dysplasia by the ANK3 gene heterozygous mutation in the First Hospital of Jilin University were retrospectively analyzed.A female newborn at 10 minutes presented for postnatal asphyxia and 10 minutes after resuscitation.She had a special appearance, with little spontaneous breathing, no swallowing, extremely low muscular tension, and no primal reflexes.Amplitude integrated electroencephalogram(aEEG) suggested the burst suppression (BS) background activity, BS (+ ), lower boundary at 2 μV, upper boundary at 50 μV, no sleep awakening cycle, no convulsive seizure, and mechanical brush seen in the original electroencephalogram burst.Severe abnormal aEEG was detected.Gene results suggested 2 heterozygous mutations in the ANK3 gene [c.4183(exon33) C >G and c. 8239(exon37) C >T], which have not been previously reported.This case report for the first time reported the clinical phenotype of the ANK3 gene mutation in the newborn with congenital dysplasia.

[Expression of receptor activator of nuclear factor-κB ligand in keratocystic odontogenic tumor before and after decompression].

PURPOSE: To investigate the expression of receptor activator of nuclear factor-κB ligand (RANKL) in keratocystic odontogenic tumor (KCOT) before and after decompression. METHODS: Twenty two pairs of paraffin-embeded tissue specimens of KCOT were collected and subjected to immunohistochemical analysis of RANKL.The data were analyzed with SPSS17.0 software package for paired t test. RESULTS: RANKL positive cells were observed in the preoperative KCOT epithelium. The expression of RANKL was down-regulated after decompression(P<0.05). CONCLUSIONS: Decrease of RANKL expression after decompression may facilitate the lining epithelium of KCOT transforming to normal oral mucosal epithelium.

Intestinal microbiome changes in patients with postpartum depression / 西安交通大学学报(医学版)

【Objective】 To analyze the changes of gut microbes in patients with postpartum depression so as to explore the relationship between postpartum depression and gut microbes. 【Methods】 A total of 60 postpartum subjects were recruited to participate in this study. The depression status of the participants was scored using the Edinburgh Postpartum Depression Scale (EPDS). Those with a score ≥13 were included in the postpartum depression group (PPD group), while those with a score less than 13 were included in the postpartum healthy control group (PPHC group). The feces of these 60 subjects were collected, and the fecal whole genome DNA was extracted for 16S rDNA sequencing. The data of changes in the bacterial diversity between the groups were obtained, and the possible correlation between the changes of intestinal microbes and postpartum depression was analyzed. 【Results】 The number of microorganisms in PPD patients was significantly reduced (P<0.001); the Chao1 index (P<0.001) and ACE index (P<0.001) of α diversity decreased significantly. There were also significant differences in β diversity between the two groups. Analysis of the bacteria in the groups showed that Acetanaerobacterium, Adlercreutzia, Allobaculum, Alloprevotella, Bifidobacterium, Christensenella, Escherichia, Eubacterium, Faecalicatena, Fusobacterium, Haemophilus, Intestinimonas, Lactobacillus, Megamonas, Monoglobumus, Muribaculum, Oscillospira, Paraprevotella, Streptococcus, Raoultibacter, Ruminococcus and Stomatobaculum were significantly enriched in PPHC group. In contrast, Kineothrix, Lachnoclostridium, Acinetobacter, Aquisphaera, Enterococcus, and Mucispirillum were enriched in PPD group. RDA/CCA analysis showed that EPDS was positively correlated with Prevotella, Kineothrix, and Alistipes, but negatively correlated with Lachnospira. 【Conclusion】 This study found that the intestinal flora of patients with postpartum depression was significantly disrupted, and there was a correlation between the intestinal flora and postpartum depression symptom score. Therefore, intestinal microbial markers may contribute to the diagnosis and treatment of patients with postpartum depression.

Effect of Yiqi Yangyin Prescription on Lipid Metabolism in Rats with Type 2 Diabetes / 中国实验方剂学杂志

Objective:To observe the effect of Yiqi Yangyin prescription on lipid metabolism in type 2 diabetes rat model induced by high fat diet combined with intraperitoneal injection of streptozocin （STZ）， and explore its mechanism in regulation of lipid metabolism. Method:The rats were fed with high-fat diet for 4 weeks， and intraperitoneal injection of STZ was provided to establish diabetes model. The diabetic rats were randomly divided into model group， Yiqi Yangyin prescription high dose group， medium dose group and low dose group （9.00， 4.50， 2.25 g·kg^-1） and metformin group （0.20 g·kg^-1）. Another blank control group was set up. The high， medium and low dose groups were given with different oral doses of Yiqi Yangyin prescription granules， metformin was given in metformin group， the model group and the blank group received the same volume of normal saline. Intragastric administration was given for three weeks， and then the weight and blood glucose were measured. Automatic biochemical analyzer was used to detect triglyceride （TG）， total cholesterol （TC）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and content of total protein （TP）. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of liver tissues in each group. Periodic acid-schiff stain （PAS） staining was used to observe the pathological changes of liver glycogen. The lipid changes of liver tissues were observed by oil red O staining. The expression of adenosine monophosphate activated protein kinase （AMPK）/ sterol regulatory element binding protein 1c （SREBP1c）/acetyl-coenzyme A carboxylase （ACC1）/peroxisome proliferator activated re-ceptor <italic>α</italic> （PPAR<italic>α</italic>） pathway in liver tissues was observed by Western blot. Result:Compared with the blank group， TG， CHO， LDL-C， AST， ALT and ALP significantly increased and HDL-C significantly decreased in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， TG and LDL-C contents significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）and LDL-C contents significantly increased in Yiqi Yangyin prescription groups （<italic>P</italic><0.05）. Histomorphology showed that Yiqi Yangyin prescription significantly reduced the degree of hepatocyte intercellular vacuoles and steatosis in liver， and significantly reduced the lipid area of liver tissue. Compared with the blank group， the protein expression levels of p-AMPK<italic>α</italic>， PPAR<italic>α</italic>， SREBP-1 （plasma） in the liver tissues significantly decreased in the model group， but such expression levels increased after treatment with Yiqi Yangyin prescription （<italic>P</italic><0.05， <italic>P</italic><0.01）， compared with the blank group， the protein expression levels of p-ACC1 and SREBP-1 （nuclear） significantly increased （<italic>P</italic><0.01） in model group， but such expression significantly decreased after treatment with Yiqi Yangyin prescription （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Yiqi Yangyin prescription can significantly reduce blood lipid in the diabetic rats caused by high-fat feed combined with STZ. The decrease of blood lipid in the type 2 diabetes rats may be related to the influence on AMPK/ACC1/SREBP-1/PPAR pathway in rat liver.

Regulatory T cells, especially ICOS+ FOXP3+ regulatory T cells, are increased in the hepatocellular carcinoma microenvironment and predict reduced survival.

Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3+, CD4+, and CD8+ cytotoxic lymphocytes (CTLs) as well as CD56+ NK cells and CD68+ macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3+ (FOXP3+) Tregs were found in intratumoural tissue. Additionally, regarding ICOS+ FOXP3+ Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3+ cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3+ Tregs/CD4+ T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3+ Tregs, especially ICOS+ FOXP3+ Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC.

Drug clinical trial of COVID-19 in China: A brief analysis / 中国临床药理学与治疗学

AIM: To provide suggestion for research and development of drugs against coronavirus disease 2019 (COVID-19) by analyzing the characteristics of the drug clinical trial registration information of COVID-19 in China. METHODS: The clinical trials of COVID-19 were searched from Chinese Clinical Trial Registry, and the type, purpose, and design of the studies were analyzed. RESULTS: Totally 271 drug clinical trials have been registered till July 1st, 2020. Most of the drugs are marketed ones, including chemical drugs, traditional Chinese medicines, and biologics. Combined applications were adopted in some projects. Randomized or non-randomized parallel control trials were conducted in most projects. Others included single arm, sequential, and factorial design. CONCLUSION: To deal with the epidemic, it is important to conduct emergent drug clinical trials to find out effective drugs as soon as possible. However, some weaknesses and deficiencies on trials design, conduct and supervision were exposed in the drug clinical trials against COVID-19. It is suggested to enhance the scientific evaluation of candidate drugs, standardize the investigator initiated trials, and establish the national multi-subject research and development platform, and the collaborative and innovative key-task tackling mechanism, thus to improve the ability and level of antiviral drug research and development.

[Effects of ginsenoside-Rb on blood lipid metabolism and anti-oxidation in hyperlipidemia rats].

OBJECTIVE: To observe effects of ginsenoside-Rb (G-Rb) on total cholesterol, lipoprotein cholesterol metabolism and anti-oxidation in experimental hyperlipidemia rats. METHOD: Hyperlipidemia rats were respectively given G-Rb 50, 100, 200 mg x kg(-1) x d(-1) ig for twelve days. Total cholesterol, lipoprotein cholesterol and lipid peroxidation (LPO) contents, prostacycline (PGI2), thromboxane (TXA2), superoxide dismutase (SOD) and blood viscosity were measured. Fat accumulation in liver was also observed. RESULT: Triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) in serum, TXA2 in plasma, LPO in serum and liver, and blood viscosity were decreased significantly. High density lipoprotein cholesterol (HDLc) in serum, PGI2 in plasma and SOD in serum and liver were significantly increased by G-Rb (100, 200 mg x kg(-1)) in experimental hyperlipidemia rats. In addition, G-Rb could decrease TC/HDL-c, LDLc/HDL-c ratio, increase PGI2/TXA2 ratio and inhibit fat accumulation in liver. CONCLUSION: G-Rb could have anti-arteriosclerosis effect by improving cholesterol and lipoprotein-cholesterol metabolism, suppressing lipid peroxidation, increasing anti-oxidase activity and PGI2/TXA2 ratio.

Role of international academic communication of pharmacology in scientific and technological innovation / 中国药理学通报

This article is to investigate the role of international academic communication of pharmacology in scientific and technological innovation. The object, the organization mode and the characteristics of international conferences of pharmacology, as well as their effects on pharmacology, were researched and analyzed. As shown in the text, international academic communication plays a key role in promoting scientific and technological development, such as pharmacological theory and technological creativity, new drug research and development, talents cultivation , etc. On the basis of the analysis, this paper suggests how to promote scientific and technological innovation, talents cultivation, and international discourse power through international academic exchange.

A clinical study of endoscopic balloon dilation in treatment of esophageal stenosis after neonatal esophageal atresia surgery / 中华消化内镜杂志

Objective To explore the feasibility and efficacy of endoscopic balloon dilation in treatment of esophageal stenosis caused by operation of congenital esophageal atresia. Methods A retrospective analysis was performed on data of 218 children with type Ⅲ esophageal atresia, who underwent surgery in Zhengzhou Children' s Hospital from January 2009 to December 2017. The occurrence of postoperative complications and efficacy of endoscopic balloon dilation in treatment of esophageal stenosis was analyzed. Results Among the 218 patients with congenital esophageal atresia, 92 were type Ⅲa and 126 were type Ⅲb. Postoperative anastomotic leakage occurred in 46 cases (21. 1％), including 29 (31. 5％) of type Ⅲa and 17 (13. 5％) of type Ⅲb. Postoperative anastomotic stenosis occurred in 53 cases (24. 3％), including 29 ( 31. 5％) of type Ⅲa and 24 ( 19. 0％) of typeⅢb. The incidence of anastomotic leakage and anastomotic stenosis in different types was significantly different (χ2=10. 383, P=0. 001; χ2=4. 497, P=0. 034). The 53 cases of anastomotic stenosis underwent 123 times of endoscopic balloon dilation, with mean time of 3. 5±1. 6, and were finally clinically recovery. No esophagus perforation occurred. Among them, 29 cases of type Ⅲa underwent 73 times with mean of 4. 0±1. 8, and 24 cases of type Ⅲb underwent 50 times with mean of 2. 5±0. 7. The difference between the two types was statistically significant (t=-4. 053, P=0. 027). Conclusion Children with type Ⅲa esophageal atresia has a higher incidence of anastomotic stenosis and leakage, and more times of esophageal dilation. Endoscopic balloon dilation is safe and effective in treatment of esophageal stenosis after surgery for patients with congenital esophageal atresia.

Strategies of preserving urinary continence in transurethral plasmakinetic enucleation of the prostate for benign prostate hyperplasia / 中华男科学杂志

Objective@#To explore the strategies of preserving urinary continence in transurethral plasmakinetic enucleation of the prostate (PKEP) for benign prostate hyperplasia (BPH).@*METHODS@#We treated 65 BPH patients by PKEP with preservation of urinary continence (UC-PKEP), which involved protection of the external urethral sphincter in the beginning of surgery, proper preservation of the anterior lobe of the prostate to protect the internal urethral sphincter in the middle, and preservation of the integrity of the bladder neck towards the end. We compared the postoperative status of urinary continence of the patients with that of the 54 BPH cases treated by complete plasmakinetic enucleation of the prostate (Com-PKEP).@*RESULTS@#All the operations were performed successfully with the urinary catheters removed at 5 days after surgery. In comparison with Com-PKEP, UC-PKEP achieved evidently lower incidence rates of urinary incontinence at 24 hours (31.49% vs 13.85%, P 0.05), and 3 months (3.70% vs 0%, P >0.05) after catheter removal. Compared with the baseline, the maximum urinary flow rate (Qmax) was significantly improved postoperatively in both the Com-PKEP (［7.43 ± 3.26］ vs ［20.58 ± 3.22］ ml, P <0.05) and the UC-PKEP group (［8.04 ± 2.28］ vs ［20.66 ± 3.08］ ml, P <0.05).@*CONCLUSIONS@#Transurethral PKEP is a safe and effective method for the management of BPH, during which the strategies of avoiding blunt or sharp damage to the external urethral sphincter in the beginning, properly preserving the anterior lobe of the prostate in the middle and preserving the integrity of the bladder neck towards the end may help to achieve rapid recovery of urinary continence.

Lipoxin A4 attenuates brain damage and downregulates the production of pro-inflammatory cytokines and phosphorylated mitogen-activated protein kinases in a mouse model of traumatic brain injury.

The present study was designed to investigate the effects of lipoxin A4 (LXA4) on traumatic brain injury (TBI) and to analyze the possible mechanism. Outcome parameters consist of blood-brain barrier (BBB) breakdown, brain edema and lesion volume. Using western blot and quantitative real-time PCR, we examined the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) and activation of mitogen-activated protein kinases (MAPKs) (including ERK, JNK, p38) following TBI. To investigate the cell types in which the LXA4 receptor (ALXR) staining was localized, brain sections pulsed with ALXR were subjected to immunofluorescence staining with antibodies against cell type-specific antigens. Our findings show that LXA4 decreases BBB permeability, attenuates brain edema, and reduces TBI-induced lesion volume. In addition, LXA4 inhibits TBI-induced elevation of mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6). In the injured cortex at 24h post-TBI, the phosphorylated-ERK (p-ERK) and -JNK (p-JNK), but not -p38 (p-p38) levels were increased. The p-ERK and p-JNK production were attenuated by their respective inhibitors (PD98059 and SP600125), as well as LXA4. Moreover, ALXR was found to label more GFAP positive cells, whereas few CD11b-positive cells were labeled by ALXR within the layers of the injured cortex at 24h post-TBI. The activation of ALXR in astrocytes was partially enhanced by LXA4 treatment. Taken together, these data indicate that TBI activates pro-inflammatory cytokines, the MAPK pathways together with ALXR in astrocytes, and these mechanisms may be exploited by pharmacological interventions.

A clinical study of traditional Chinese medicine of fumigation and washing combined with thymalfasin and isotretinoin treatment for verruca plantaris / 国际中医中药杂志

Objective To evaluate the clinical effect of the homemade traditional Chinese medicine bathing prescription combined with Thymalfasin and Isotretinoin treatment for Verruca Plantaris.Methods A total of 120 patients with Verruca Plantaris were randomly divided into 3 groups according to the random number table method (each group 40). The drug therapy group was given Thymalfasin and Isotretinoin to treatment; and the Chinese medicine washing group was given traditional Chinese medicine wash-out on the basis of drug therapy; and the physical therapy group was given liquid nitrogen freezing treatment on the basis of drug therapy. All the groups were treated 12 weeks and follow-up 3 months. Four weeks were a course, and a total of 3 courses. After the treatment, the symptom grading scores (number of skin lesions, the size of skin lesions, the degree of pain and the quality of life) was compared, and the clinical effect rate was evaluated and the recurrence rate was observed.Results Twelve weeks after treatment, Chinese medicine washing group total effective rate was 97.5% (39/40), drug treatment group 87.5% (35/40), and physical treatment group 90.0% (36/40). The Chinese medicine washing group total effective rate was superior to the drug therapy and physicaltherapy groups (Z values were -3.463,-3.122,P values were 0.001, 0.002). after treatment, the number of lesions scores (2.0 ± 1.1 vs. 2.8 ± 1.5, 2.7 ± 1.6,F=3.787), the size of the lesion scores (2.3 ± 1.7 vs. 3.2 ± 1.3, 3.1 ± 1.3, F=4.657), pain degree and the quality of life scores (0.4 ± 0.5 vs. 1.0 ± 1.2, 1.0 ± 1.0,F=5.353) in the Chinese medicine washing group were significantly higher than those in the drug therapy and physical therapy groups (P<0.01). After follow-up period, the recurrence rate of Chinese medicine washing group was 10.3% (4/39), the drug treatment group 25.7% (9/35), the physical therapy group 41.7% (15/36). The difference among 3 groups was statistically significant (Z=-3.188,P<0.01).Conclusions The traditional Chinese medicine combined with Thymalfasin and Isotretinoin could reduce the number of skin lesions, narrow the range of skin lesions and reduce the degree of pain, and improve the quality of life.