Protective efficacy of a novel multivalent vaccine in the prevention of diarrhea induced by enterotoxigenic Escherichia coli in a murine model

Background@#Enterotoxigenic Escherichia coli (ETEC) infection is a primary cause of livestock diarrhea. Therefore, effective vaccines are needed to reduce the incidence of ETEC infection. @*Objectives@#Our study aimed to develop a multivalent ETEC vaccine targeting major virulence factors of ETEC, including enterotoxins and fimbriae. @*Methods@#SLS (STa-LTB-STb) recombinant enterotoxin and fimbriae proteins (F4, F5, F6, F18, and F41) were prepared to develop a multivalent vaccine. A total of 65 mice were immunized subcutaneously by vaccines and phosphate-buffered saline (PBS). The levels of specific immunoglobulin G (IgG) and pro-inflammatory cytokines were determined at 0, 7, 14 and 21 days post-vaccination (dpv). A challenge test with a lethal dose of ETEC was performed, and the survival rate of the mice in each group was recorded. Feces and intestine washes were collected to measure the concentrations of secretory immunoglobulin A (sIgA). @*Results@#Anti-SLS and anti-fimbriae-specific IgG in serums of antigen-vaccinated mice were significantly higher than those of the control group. Immunization with the SLS enterotoxin and multivalent vaccine increased interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations. Compared to diarrheal symptoms and 100% death of mice in the control group, mice inoculated with the multivalent vaccine showed an 80% survival rate without any symptom of diarrhea, while SLS and fimbriae vaccinated groups showed 60 and 70% survival rates, respectively. @*Conclusions@#Both SLS and fimbriae proteins can serve as vaccine antigens, and the combination of these two antigens can elicit stronger immune responses. The results suggest that the multivalent vaccine can be successfully used for preventing ETEC in important livestock.

A review of platelet-rich plasma in the treatment of rotator cuff injury / 中华骨科杂志

Rotator cuff injury is one of the common injuries of the shoulder joint. The tendon-bone interface is the special organizational structure of the multi-layer structure of bone, fibrocartilage and tendon. Further, it has stress concentration point. Thus, rotator cuff injury is often difficult to heal spontaneously once injuries and it has a higher re-tear rate after surgical intervention. Platelet-rich plasma (PRP) is obtained by concentrating autologous whole blood. Its platelet concentration is higher than the baseline level of whole blood. It also contains various growth factors and other blood components. At present, it has been widely used in treating orthopedics, skin and oral disorders. In recent years, the application of PRP in rotator cuff injury has attracted attention. PRP can assist the treatment of rotator cuff injury in regulating inflammation, angiogenesis, matrix synthesis and tissue remodeling. The use of PRP after rotator cuff repair can improve the postoperative shoulder joint function score, relieve postoperative pain in the short term, and effectively reduce the rotator cuff re-tear rate. However, the efficacy of PRP in treating rotator cuff injuries is affected by many factors, such as the type of PRP, the severity of rotator cuff tear, and different using approaches. Currently, we focus on PRP in the treatment of rotator cuff injury, aiming to systematically explain the differences among different studies and reveal the differences in the efficacy of PRP with varied components and different forms of administration. Moreover, we want to provide a reference for the proper and rational use of PRP in the treatment of various rotator cuff injuries. Meanwhile, the present review could provide a basis for future researches in the application of PRP for rotator cuff injury.

Protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae against myocardial injury in septic mice / 南方医科大学学报

OBJECTIVE@#To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.@*METHODS@#Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.@*RESULTS@#Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05).@*CONCLUSION@#Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.

Short-term effectiveness and dosimetry evaluation for 125I seeds implantation in treatment of lymph nodes metastasis from radioactive iodine-refractory differentiated thyroid carcinoma / 中华核医学与分子影像杂志

Objective:To evaluate the efficacy and safety of 125I seeds implantation for lymph nodes metastasis (LNM) from radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC), and to verify the computer three-dimensional treatment planning system (TPS) from the dosimetry accuracy in assisting seeds implantation to treat LNM. Methods:Retrospective analysis was performed on 17 RAIR-DTC patients with LNM admitted to the General Hospital of Northern Theater Command from December 2016 to January 2019 (8 males, 9 females, median age 58 years). All patients underwent preoperative TPS planning design, CT-guided puncture and 125I seeds implantation (seed activity 14.8-25.9 MBq). The dosimetric results of postoperative validation were compared with those of preoperative planning, including the dosimetric parameters such as target volume before and after surgery and the dose received by 90% and 100% gross tumor volume (GTV) ( D90, D100), the percentage received by 100% and 150% of the prescription dose ( V100, V150), homogeneity index (HI). All patients underwent CT after 6 months to compare the LNM size, serum thyroglobulin (Tg) level, and the improvement of complications before and after treatment. Efficacies were divided into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). Paired t test or Wilcoxon signed rank test were used to analyze the data. Results:Among 17 patients, a total of 226 125I radioactive seeds were implanted. Among them, 1 achieved CR, 10 achieved PR, 4 were with SD, and 2 were with PD. The diameter of LNM was 1.40(0.65, 3.05) cm before treatment and was 0.40(0.21, 0.91) cm 6 months after treatment ( z=-3.95, P<0.05). The Tg before treatment was 23.50(20.94, 72.92) μg/L and was 8.90(3.20, 40.22) μg/L 6 months after treatment ( z=-5.009, P<0.001). Tg antibody were all negative. There were 90.90% (20/22) of patients had slightly lower D90 than the prescribed dose ((12 378.8±3 182.0) vs (12 497.8±1 686.4) cGy; t=0.251, P>0.05). The postoperative dose parameters D100 and V150 ((6 881.5±1 381.8) cGy, (58.5±18.4)%) were both lower than those of preoperative plan ((8 085.8±2 330.0) cGy, (66.5±17.7)%; t values: 8.913, 3.032, both P<0.05), and the remaining indicators were not significantly different from those of the preoperative plan ( t values: 0.251, 1.493, z values: from -1.604 to -0.593, all P>0.05). Conclusions:According to the TPS preoperative plan, 125I seeds implantation for treating RAIR-DTC LNM can achieve the expected dose distribution, and the short-term tumor local control is effective. It is a safe and effective treatment method.

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.

AncPhore: A versatile tool for anchor pharmacophore steered drug discovery with applications in discovery of new inhibitors targeting metallo-

We herein describe AncPhore, a versatile tool for drug discovery, which is characterized by pharmacophore feature analysis and anchor pharmacophore (

Multidisciplinary and Comprehensive Chinese Medicine for Advanced Non-Small Cell Lung Cancer Patients: A Retrospective Study of 855 Cases / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of multidisciplinary and comprehensive Chinese medicine (CM) treatments on progression-free survival (PFS) and median survival time (MST) in patients with advanced non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis.@*METHODS@#Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed. Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection. Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling. Key factors correlated to progression and prognosis were screened out, and a Cox proportional hazard model was established to calculate the prognostic index.@*RESULTS@#The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months, respectively. The 1-, 2-, 3-, and 5-year survival rates were 79.2%, 54%, 36.2%, and 17.1%, respectively. Gender, pathologic type, and clinical stage were independent prognostic risk factors; surgical history, radiotherapy, treatment course of Chinese patent medicine, intravenous drip of Chinese herbal preparation, duration of oral administration of Chinese herbal decoction (CHD), and intervention measures were independent prognostic protective factors. Gender was an independent risk factor for progression, while operation history and oral CHD administration duration were independent protective factors (all P<0.05). Women with stage IIIb-IIIc lung adenocarcinoma had the best outcomes.@*CONCLUSIONS@#Female patients have lower progression risk and better prognoses than male patients, younger patients have higher progression risk but better long-term prognoses than the elderlys, and patients with lower performance status scores are at lower risk for progression and have better prognoses. Comprehensive CM treatments could significantly reduce progression risk, improve prognosis, and prolong survival time for patients with advanced NSCLC. This treatment mode offers additional advantages over supportive care alone.

Oxytocin receptor variant rs53576 genotype is associated with dysphoric arousal symptoms of DSM-5 posttraumatic stress disorder in Chinese earthquake survivors / 中华创伤杂志(英文版)

PURPOSE@#Evidence suggests that the oxytocin receptor (OXTR) gene may be involved in the psychopathology of posttraumatic stress disorder (PTSD). This study aimed to investigate the effects of OXTR rs53576 genotype on PTSD symptoms introduced in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5).@*METHODS@#This study was a cross-sectional study conducted among 1140 adults who had personally experienced the Wenchuan earthquake. PTSD symptoms were measured with the PTSD checklist for DSM-5. A custom-by-design 2 × 48-Plex SNPscan@*RESULTS@#The results revealed that the rs53576 genotype could significantly predict PTSD symptoms (β = 0.055, p = 0.045). Further analysis showed that the rs53576 genotype was only significantly associated with dysphoric arousal symptoms of PTSD (β = 0.080, p = 0.005). The rs53576 genotype × earthquake exposure interaction had no significant effect on different symptom clusters (p > 0.05).@*CONCLUSION@#This study showed that the rs53576 genotype was only associated with the dysphoric arousal symptoms but not with other symptom clusters of PTSD. These findings support the role of the OXTR on the psychopathology of PTSD and help us to understand the genetic basis of PTSD.

Efficacy of Hybrid anterior cervical spine surgery on range of motion and curvature in the treatment of cervical degenerative diseases / 中国骨伤

OBJECTIVE@#To observe the change of cervical curvature and range of motion (ROM) on imaging at 6 months after Hybrid surgery.@*METHODS@#A total of 29 patients with cervical degenerative disease who underwent Hybrid surgery from January 2017 to July 2018 were retrospectively analyzed. Also, they all met the inclusion criteria and had complete preoperative and 6 months postoperative imaging data. There were 11 males and 18 females, aged from 34 to 76 (55.86±10.69) years, and the operation time was from 2 to 4(3.03±0.51) hours. The Cobb angle method was used to measure the changes of cervical curvature and ROM of C@*RESULTS@#There was no statistically significant difference in C@*CONCLUSION@#Hybrid surgery reconstructs the lordotic curvature of the entire cervical spine and the responsible segment, retains the ROM of the cervical replacement segment, and restores the biomechanical function of cervical spine.

Chinese Medicine in Fighting against Covid-19: Role and Inspiration / 中国结合医学杂志

Covid-19 pandemic has caused hundreds of thousands deaths and millions of infections and continued spreading violently. Although researchers are racing to find or develop effective drugs or vaccines, no drugs from modern medical system have been proven effective and the high mutant rates of the virus may lead it resistant to whatever drugs or vaccines developed following modern drug development procedure. Current evidence has demonstrated impressive healing effects of several Chinese medicines (CMs) for Covid-19, which urges us to reflect on the role of CM in the era of modern medicine. Undoubtedly, CM could be promising resources for developing drug candidates for the treatment of Covid-19 in a way similar to the development of artemisinin. But the theory that builds CM, like the emphasis of driving away exogenous pathogen (virus, etc.) by restoring self-healing capacity rather than killing the pathogen directly from the inside and the 'black-box' mode of diagnosing and treating patients, is as important, yet often ignored, an treasure as CM herbs and should be incorporated into modern medicine for future advancement and innovation of medical science.

Challenges in treatment of massive rotator cuff tear in the elderly / 中华创伤杂志

The rotator cuff of the elderly always is significantly degenerated and often accompanied by osteoarthritis, muscle weakness and muscle atrophy. Rotator cuff tear is the most common cause of shoulder pain. The incidence of massive rotator cuff tear is high in the elderly. Damaged rotator cuff tissue is difficult to repair with a high retear rate after surgical repair, which seriously reduces the quality of life of patients. Therefore, the authors focus on a brief overview of the characteristics, treatment choices, and rehabilitation exercises of the aged patients with massive rotator cuff tear so as to provide references for treating massive rotator cuff tear in the elderly.

Clinical observation on the treatment of cervical degenerative diseases with Hybrid surgery / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of anterior cervical Hybrid surgery in the treatment of cervical degenerative diseases (CDD) and observe the incidence of heterotopic ossification of disc replacement segment at 1 year after surgery.@*METHODS@#From January 2015 to April 2018, 35 patients who received anterior cervical hybrid surgery met the inclusion and exclusion criteria and the complete clinical follow up data were analyzed retrospectively. Complete imaging follow-up data were obtained from 24 patients. There were 15 males and 20 females, aged from 39 to 70(55.57±7.73) years old. The amount of bleeding was for 20 to 100 (40.29±18.39) ml, and the hospitalstay was for 4 to 28(11.03±4.63) days, and the follow-up time was(12.97±1.36) months. Clinical outcomes were assessed by the Tanaka Yasushi cervical spondylitis symptom scale 20 score (YT20), and Japanese Orthopaedic Association (JOA) score. The occurrence of heterotopic ossification after Hybrid surgery was evaluated by X-ray according to McAfee standard one year after operation. Patients with or without heterotopic ossificationwere divided into two groups and their clinical effects were compared.@*RESULTS@#At the final follow up, the mean YT20 score and JOA score were significantly higher than those before operation (P <0.05), and the average improvement rate of JOA was (70.66 ±0.44)%. One year after operation, the heterotopic ossification occurred in 10 of 24 segments, with incidence of 41.70%(10/24), including 29.20% in gradeⅠand 12.50% in gradeⅡ. The results of clinical efficacy comparison between patients with and without heterotopic ossification were as follows:there was no significant difference in JOA score before and after operation (@*CONCLUSION@#The short-term clinical effect of Hybrid surgery is satisfactory for cervical degenerative diseases, and the cause of heterotopic ossification still needs tobe further explored.

Mechanism of Sanqi Mixture for intervention in hepatic ischemia reperfusion injury based on network pharmacology / 中草药

Objective: Through network pharmacology, the network relationship between the active component of Sanqi Mixture, the target of hepatic ischemia- reperfusion injury(HIRI), and biological pathway was constructed to explore the key target and mechanism of effect of Sanqi Mixture on HIRI. Method: Through literature research at home and abroad, Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform, Pharm Mapper, Swiss Target Prediction and other servers, oral availability (OB) and drug-likeness (DL) were selected as the limited conditions to collect the relevant targets for Sanqi Mixture for intervention in HIRI. The OMIM database was used to screen and collate HIRI related genes and protein targets. Excel table was used to merge and sort the intersection between disease and targets through Cytoscape3.7.2 software plug-ins Network Analyzer, with topological parameters (degree) ≥ 5 (average degrees of freedom 4.5) for the filter to find the core targets; And the intersection targets were imported to the server STRING, and with Confidence Score of 0.85 or higher for the filter conditions to build the core protein interactions (Hub-PPI) network. The intersection target was introduced into FunRich 3.0 software for biological process and biological pathway analysis, and Cytoscape3.7.2 was used to construct the network of "traditional Chinese medicine-active ingredient-HIRI target-biological pathway". Result: Sanqi mixture could reduce the expression of Aspartate aminotransferase (AST) and glutamate transaminase (ALT) in HIRI mice (P < 0.01). After screening, 45 active components of Sanqi Mixture were obtained, corresponding to 3 273 targets, and the main compounds included ursolic acid, oleanolic acid, brucine, quercetin, ginsenoside F2, paeoniflorin, etc. Among the 196 targets obtained by HIRI, 46 targets were intersected with components, including 11-β-hydroxysteroid dehydrogenase (HSD11B1), adenosine receptor A3 (ADORA3), cyclooxygenase 2 (PTGS2), adenosine receptor A1 (ADORA1), protein kinase C-ε (PKC), etc. With the STRING server setting the qualified condition of Confidence Score ≥ 0.85, the PPI network with high Confidence was obtained and clustered into three categories through cluster processing. Five biological processes including protein metabolism, signal transduction, negative regulation of enzyme activity, inflammatory response and transmembrane receptor protein tyrosine kinase signal pathway were analyzed by FunRich software (P < 0.05). 16 biological pathways including integrin-linked kinase signal, TNF receptor signaling pathway, P38 mitogen-activated protein kinase signaling pathway, and TRAIL signaling pathway (P < 0.01). Conclusion: It is preliminarily discussed that Sanqi Mixture intervenes HIRI through the interaction of multiple components and multiple targets, as well as the regulation of multiple biological pathways and biological processes. However, the key core targets and the specific regulation mechanism still need further experimental verification.

Application of pulmonary ultrasound in the diagnosis of COVID-19 pneumonia in neonates / 中华儿科杂志

Objective To investigate the application of pulmonary ultrasound in the diagnosis of neonatal novel coronavirus pneumonia (COVID-19). Methods In this retrospective study, the clinical data of 5 infants, who were admitted to the Department of Neonatology in Wuhan Children's hospital from 31 th January to 25 th February 2020, were collected. Bedside pulmondary ultrasound was conducted on admission, during the hospitalization, and before discharge, and the result were compared with the chest X-ray or CT done at the same time. Results Among the 5 cases who aged 1-18 days, 3 were male. The main clinical manifestations were respiratory and gastrointestinal symptoms. The pulmonary ultrasonography on admission showed abnormal pleural line and pulmonary edema of different severity in all 5 cases, presented as increase and fusion of B-line, and pulmonary interstitial syndrome; among them, one case also had a small-range consolidation. The chest CT on admission showed no obvious parenchymal infiltration in 2 cases, small strip or patchy high-density shadow in 2 cases, and ground glass change in one case. The re-examination of ultrosound during the hospitalization and at discharge showed improvement in all cases and were consistent with the chest X-ray taken at the sametime. Conclusions The main changes on the pulmonary ultrasonography in neonates with COVID-19 pneumonia are increase and fusion of B-line, abnormal pleural line, and nalveolar interstitial syndrome, and may combined with small range of pulmonary consolidation. The sensitivity of pulmonary ultrasound is higher than chest X-ray and CT in the diagnosis of pulmonary edema, and could be used in monitoring and evaluation of the disease.

Role of microglial pyroptosis in hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To investigate the role of microglial pyroptosis in hypoxic-ischemic brain damage.@*METHODS@#An oxygen-glucose deprivation/reoxygenation (OGD/R) model of rat microglial cells were cultured in vitro. Western blot was used to measure the expression of the pyroptosis-related proteins caspase-1, interleukin-1β (IL-1β), and N-terminal gasdermin D (GSDMD-N) at 0, 1, 3, 6, 12, and 24 hours after OGD/R. After the microglial cells were transfected with lentivirus-mediated silenced gasdermin D (GSDMD), immunofluorescence assay and Western blot were used to measure the transfection rate of GSDMD. Microglial cell lines were divided into three groups: normal control, negative control, and LV-sh_GSDMD (lentivirus-mediated GSDMD silencing). CCK-8 assay and LDH kit were used to observe the effect of GSDMD silencing on the viability and toxicity of microglial cells at 24 hours after OGD/R. Western blot was used to observe the effect of GSDMD silencing on the levels of caspase-1, GSDMD-N, and IL-1β in the microglial cells at 24 hours after OGD/R.@*RESULTS@#The expression levels of the pyroptosis-related proteins caspase-1, GSDMD-N, and IL-1β in microglial cells were upregulated since 0 hour after OGD/R and reached the peak levels at 24 hours. A microglial cell model of lentivirus-mediated GSDMD silencing was successfully constructed. At 24 hours after OGD/R, compared with the normal control group, the GSDMD silencing group had a significant increase in the cell viability and a significant reduction in the cytotoxicity (P<0.05), as well as significant reductions in the protein expression levels of caspase-1, GSDMD-N, and IL-1β in microglial cells (P<0.05).@*CONCLUSIONS@#Lentivirus silencing of the key substrate protein for pyroptosis GSDMD can alleviate hypoxic-ischemic brain damage, suggesting that microglial pyroptosis aggravates hypoxic-ischemic brain damage.

A New Perspective for Chinese Medicine Intervention for Coronary Artery Disease: Targeting Inflammation / 中国结合医学杂志

Inflammation, which plays a critical role in atherosclerosis and the occurrence of acute cardiovascular events, may be a new target for treatment of coronary artery disease (CAD) to reduce residual cardiovascular risk. Recently, Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS), the largest scale clinical trial that targeted inflammation but not lipids, has affirmed for the first time the inflammatory hypothesis of artherosclerosis and marked the advent of an exciting era of targeting inflammation for the prevention and treatment of cardiovascular diseases. Chinese medicine (CM) is a promising adjuvant therapy for CAD in light of its safety and pleiotropic effect of anti-inflammation, anti-platelet, lipid-regulating, endothelium-protection, microcirculation-improving, etc. In recent years, exploration of anti-inflammatory treatment of CAD with CM has been going on from theory to practice. Taking CANTOS as an example, the design strategy to combine CM and Western medicine to inhibit inflammation were discussed in this paper, which might provide a new perspective for CM intervention on CAD.

Analysis of KIAA0196 gene mutation in a family with hereditary spastic paraplegia / 中华医学遗传学杂志

OBJECTIVE@#To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey.@*METHODS@#Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members.@*RESULTS@#Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet.@*CONCLUSION@#The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.

Applicatoin progress on click chemistry in targets identification of bioactive components from Chinese materia medica / 中草药

The target is the basis for the active ingredients of Chinese materia medica (CMM), which plays an important role in the patients’ body. Target identification is the key work for the development of CMM. However, the current studies on the target of CMM are still limited, and it has become a bottleneck in the modernization of CMM. Therefore, new ideas and new technologies are required for the research on targets. Recently, a new method for the study of targets has been provided by the technology of activity-based protein profiling represented by click chemistry. The application of click chemistry in target identification of CMM in recent years is briefly reviewed and summarized, and the trends of application and development of click chemistry are prospected in this review.

Feiji Recipe inhibits the growth of lung cancer by modulating T-cell immunity through indoleamine-2,3-dioxygenase pathway in an orthotopic implantation model / 中西医结合学报

<p><b>OBJECTIVE</b>Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe.</p><p><b>METHODS</b>An orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein (2LL-EGFP) and 2LL-EGFP-IDO were investigated, and the apoptosis of T-cells was examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high-performance liquid chromatography.</p><p><b>RESULTS</b>Compared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged (P = 0.0074), and the IDO protein level decreased (P = 0.0072); moreover, the percentages of CD4CD25 T-cells and Foxp3 T-cells were significantly decreased (P < 0.05). The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and regulatory T-cells.</p><p><b>CONCLUSION</b>The molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.</p>

Analysis of TGFBI gene mutation in a pedigree affected with corneal dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutation in a large Chinese pedigree affected with congenital corneal dystrophy.</p><p><b>METHODS</b>Two patients from the pedigree were subjected to whole exome sequencing to determine the candidate gene. Suspected mutation was verified in 13 additional members by directional Sanger sequencing. Ccorrelation between genotype and phenotype was explored.</p><p><b>RESULTS</b>A missense mutation, c.1877A>C (p.His626Pro), was detected in exon 14 of the TGFBI gene in 8 patients from the pedigree, but not in five unaffected members and 100 unrelated healthy controls. Respectively, the mutation was predicted as "affecting protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and MutationTaster.</p><p><b>CONCLUSION</b>The c.1877A>C mutation of the TGFBI gene probably underlies the disease in this pedigree.</p>