Erratum: Author correction to "YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer" Acta Pharmaceutica Sinica B 12 (2022) 2845-2858

[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

Long non-coding RNAs: From disease code to drug role

Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.

A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

Coumarin glycosides from Hydrangea paniculata slow down the progression of diabetic nephropathy by targeting Nrf2 anti-oxidation and smad2/3-mediated profibrosis.

BACKGROUND: Water extract of Hydrangea paniculata (HP) stem, rich in coumarin glycosides, has been demonstrated to have renal protective effect in several experimental kidney injury animal models. Currently, it is under pre-clinical development as a class 5 herbal drug against membranous nephropathy. However, whether it also benefits diabetic nephropathy (DN) is not clear. PURPOSE: This study was performed to investigate the protective effect of HP on streptozotocin-induced experimental DN, and further understand its molecular mechanisms. METHODS: In the present study, type 1 diabetes rat model was established by the intraperitoneal injection of streptozotocin. HP was orally administered every day for three months. Biochemical analysis and histopathological staining were conducted to evaluate the renal functions. In vivo pharmacokinetic study was conducted to analyse the metabolites of HP with high blood drug concentration. In vitro assay using these metabolites was performed to analyse their ability to reduce reactive oxygen species (ROS) production induced under high glucose (HG) condition by flow cytometry. Reverse transcription-polymerase chain reaction was conducted to analyse the mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and IL6 and western blot was performed to analyse the phosphorylation status of smad 2/3 in HK2 cells under TGFß1 stimulation. RESULTS: The treatment with HP significantly reduced the blood urea nitrogen and serum creatinine content, and urine albumin excretion in diabetic rats, and increased the creatinine clearance rate. Periodic acid-schiff and methenamine staining and immunohistochemistry revealed that HP also ameliorated glomerulosclerosis and tubular vacuolar degeneration, as well as the deposition of fibronectin and collagen IV in the glomeruli. Pharmacokinetic study results revealed that the major coumarin compounds from HP were metabolised into umbelliferone and esculetin. By in vitro assay, umbelliferone and esculetin were found to significantly decrease ROS production induced by HG content, as well as increase the mRNA level of Nrf2. HP and its metabolites also can down-regulate fibronectin secretion in HK2 cells stimulated by TGFß1 and inhibit smad2/3 phosphorylation. CONCLUSION: HP has beneficial effect on DN by increasing Nrf2 expression and inhibiting TGF-smad signal activation. Further, it can be a novel herbal drug against DN.

Nicousamide attenuates renal dysfunction and glomerular injury in remnant kidneys by inhibiting TGF-ß1 internalisation and renin activity.

Nicousamide has been shown to exert renal protective effects against diabetic nephropathy and has moved to a phase II clinical trial in China for diabetic nephropathy indication. To expand its clinical indications, 5/6-nephrectomised rats were used to mimic glomerular and vascular sclerosis and tubulointerstitial scarring, with subsequent progression towards end-stage renal disease. Adult Wistar rats underwent 5/6 nephrectomy to induce the development of chronic kidney disease, with a sham operation performed as a control. The nephrectomised animals were treated orally with either saline, nicousamide (7.5,15, or 45 mg/kg), benazepril (4 mg/kg), or losartan (10 mg/kg) daily for 20 weeks. At 8, 16, and 20 weeks of treatment, blood pressure was measured in each animal, and blood and urine samples were collected for biochemical analysis, while kidney remnants were collected for histological examination. Levels of fibronectin and transforming growth factor beta 1 (TGF-ß1) were measured in kidneys by immunohistochemistry. Renin activity in the plasma was measured by an enzyme-linked immunosorbent assay. The results showed that nicousamide treatment significantly reduced systemic hypertension, proteinuria, and blood urea nitrogen (P < 0.05), effectively alleviated glomerular sclerosis scores and tubulointerstitial injuries in a dose-dependent manner (P < 0.01), and markedly decreased fibronectin and TGF-ß1 levels in kidney tissues of the 5/6-nephrectomised animals. In vitro studies suggested that nicousamide could moderately inhibit the renin activity and strongly block the TGF-ß1 internalisation into fibroblast cells. In summary, nicousamide may protect from renal failure through dual targeting, which involves a TGF-ß1-dependent mechanism and inhibition of renin activity.

A case of imported furuncular cutaneous myiasis and cytochrome oxidase Ⅰ gene sequence analysis of the pathogenic Cordylobia anthropophaga / 中华皮肤科杂志

To report a case of imported furuncular cutaneous myiasis,and to analyze the sequence of the mitochondrial cytochrome C oxidase subunit Ⅰ (CO Ⅰ) gene of the pathogenic Cordylobia anthropophaga.A 33-year-old female patient had a travel history to Ghana and Cameroon in Africa 1 month prior to the presentation.No anti-mosquito measures were taken during her stay,and she hung up the laundries outside to dry for several times.Skin examination showed furuncular protuberances with diameters of 1-2 cm on the inner side of the left upper arm as well as on the outer side of the left chest,which were bright red and hard on palpation with irregular borders and a small hole on their central surface.Morphological identification revealed that the larva squeezed from the lesion was suspected as myiasis.After PCR amplification of the CO Ⅰ gene of the larva,an about 650-bp PCR product was acquired.Sequencing and BLAST analysis showed that this product was most closely related to the CO Ⅰ gene (GenBank accession number:FR719158.1) of Cordylobia anthropophaga isolated in Cameroon in 2010 with the sequence similarity being 99.84％,and they were grouped together on the phylogenetic tree.According to the clinical features and travel history of the patient and the sequencing results of the pathogenic Cordylobia anthropophaga,this case was confirmed as imported furuncular cutaneous myiasis caused by Cordylobia anthropophaga.

Clinical effects of arthroscopic anatomical anterior cruciate ligament reconstruction with direct insertion technique / 中国基层医药

Objective To OxplorO thO opOrating mOthods and clinical OffOcts of arthroscopic anatomical antO-rior cruciatO ligamOnt(ACL) rOconstruction with dirOct insOrtion tOchniquO vOrsus traditional mOthod.Methods From January 2017 to DOcOmbOr 2017,totally 52 patiOnts who accOptOd ACL rOconstruction and mOt thO inclusion and Oxclu-sion critOria in BOijing FriOndship Hospital of Capital MOdical UnivOrsity wOrO OnrollOd in this rOtrospOctivO study. ThOy wOrO dividOd into two groups by random sOquOncO softwarO and patiOnts′sOlOction rOsults. ThO obsOrvation group (27 casOs) rOcOivOd dirOct insOrtion tOchniquO,and thO control group(25 casOs) rOcOivOd traditional mOthod. At post-opOrativO 1 month, 3 months, 6 months, 1 yOar, thO clinical OffOct was OvaluatOd by imaging indOx, subjOctivO and objOctivO indicators.Results All 52 patiOnts wOrO availablO for follow up with an avOragO of 11.5 months. No postop-OrativO complications such as infOction, joint instability and soft lOgs, with a satisfiOd rOcovOry of rangO of motion, pain rOliOvOd significantly. ThO Lysholm scorO of thO obsOrvation group was (94.80 ± 4.18)points, which was signifi-cantly highOr than (91.02 ± 1.96)points of thO control group (t=2.674,P<0.05).Lachman tOst and KT-1000 wOrO improvOd significantly comparOd with thosO bOforO opOration ( all P <0.01), whilO thOrO was no statistically significant diffOrOncO bOtwOOn thO two groups(all P>0.05),but thO pivot-tOst of thO obsOrvation group was bOttOr than that of thO control group, thO diffOrOncO was statistically significant ( P < 0. 05 ). ThO ACL anglO of thO obsOrvation group was (51.52 ± 5.18)°, which was significantly lowOr than (55.86 ± 2.45)° of thO control group ( P<0.05). According to modifiOd Lysholm scorOs classification, in thO obsOrvation group, 24 casOs wOrO OxcOllOnt, 2 casOs wOrO good,1 casO was fair, and thO OxcOllOnt and good ratO was 96.3%. In control group,18 casOs wOrO OxcOllOnt,5 casOs wOrO good,2 casOs wOrO fair, and thO OxcOllOnt and good ratO was 92.0%. ThO diffOrOncO in thO OxcOllOnt and good ratO bOtwOOn thO two groups was statistically significant(P<0.05).Conclusion DirOct insOrtion anatomical rOconstruction is a safO and OffOctivO tOchniquO for rOconstruction of ACL. It can rOstorO thO stability of ACL and rotation of knOO joint.

A voxel-based morphometry analysis of brainstem in patients with Alzheimer's disease / 中华神经科杂志

Objective To investigate the morphological changes of the brainstem in patients with Alzheimer's disease (AD) and their relationship with hippocampal morphological changes.Methods Sixty AD patients (AD group) and sixty age-and gender-matched normal elderly (normal control group) were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.The hippocampus and the brainstem of each subject were segmented and their normalized volumes were calculated.According to the hippocampal volume standard value (Z-score),AD patients were divided into two subgroups (hippocampal atrophy group (n=51) and hippocampal spared group (n=9)).A voxel-based morphology (VBM) study was also performed to investigate the morphological differences of the brainstem between the normal control group and the AD group,as well as between the AD subgroups.Results Compared with the normal control group,the brainstem volume in the AD group decreased significantly (16 741.31±1 739.11 vs 15 609.67±1 451.60,t=3.870,P=0.001).In AD subgroups,the volume of the brainstem in the hippocampal atrophy group was significantly smaller than that in the hippocampal spared group (16 556.30 ± 1 514.86 vs 15 442.62 ± 1 389.05,t=2.189,P=0.033).Pearson correlation analysis showed that Mini-Mental State Examination scores were positively correlated with the hippocampal and the brainstem volumes (r=0.590,P＜0.01;r=0.234,P＜0.05),and there was a positive correlation between the hippocampal and the brainstem volume changes in patients with AD (r=0.315,P=0.014).VBM results showed that both the bilateral midbrain and the bilateral pons in the AD group had significant atrophy compared with the normal control group (P＜0.05).In the AD subgroups,the bilateral midbrain and the left pons in the hippocampal atrophy group were significantly atrophied compared with the hippocampal spared group (P＜0.05).Conclusion The brainstem showed morphological changes in patients with AD,and the morphological changes of the brainstem in AD patients with different degrees of hippocampal atrophy were different,indicating the morphological changes of the hippocampus and the brainstem may have an interrelated relationship.

Clinical distribution and antibiotic resistance of Streptococcus pneumonia isolated from pediatric patients in Guangzhou / 国际检验医学杂志

Objective To explore the sample type and drug resistance characteristics of Streptococcus pneu-monia(Spn)isolated from pediatric patients in Guangzhou district,and their age distribution to offer instruc-tions for prevention and clinical treatment.Methods Spn isolates were cultured and identified according to the national standard procedure for clinical laboratory operation,followed by analysis of sample type and age dis-tribution of pediatric patients with positive isolates of Spn in Guangzhou Women and Children′s Medical Cen-ter from 2013 Jan 1st to 2015 Dec 31st,drug resistance status was determined by MIC test.Results Totally, 1 243 strains of Spn were isolated,which were mainly from pediatric patients under 1 year old(42.80%).Spn isolates were mainly isolated from respiratory tract(72.81%),ear secretions(15.37%),blood(5.63%),cere-brospinal fluid(3.06%)and hydrothorax(2.01%).For all Spn isolates,the resistance rate to erythromycin, tetracycline and sulfamethoxazole was especially high as 94.93%,85.76%,73.53% respectively,with relative high resistance to penicillin G(24.70%),amoxicillin(39.59%),ceftriaxone(24.05%),meropenem(22.85%) and cefotaxime(19.89%),low resistance to quinolone antibiotics(<10.00%),and no resistance to vancomycin and linezolid.Conclusion The major age group of children with Spn infection is infants under one year old in Guangzhou,clinicians should be serious about the high resistant rate of Spn to erythromycin,tetracycline and sulfamethoxazole,the significantly increased resistant rate to penicillin,amoxicillin and ceftriaxone.Clinicians should choose antibiotics rationally according to the characteristics of drug sensitivity for better treatment.

Total Coumarins from Hydrangea paniculata Protect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis.

Aim. Hydrangea paniculata (HP) Sieb. is a medical herb which is widely distributed in southern China, and current study is to evaluate renal protective effect of aqueous extract of HP by cisplatin-induced acute kidney injury (AKI) in animal model and its underlying mechanisms. Materials and Methods. HP extract was prepared and the major ingredients were coumarin glycosides. AKI mouse models were established by single i.p. injection of 20 mg/kg cisplatin, and HP was orally administrated for total five times. The renal biochemical functions, pathological staining, kidney oxidative stress, and inflammatory status were measured. Apoptosis of tubular cells and infiltration of macrophages and neutrophils were also tested. Results. HP administration could improve the renal function by decreasing concentration of blood urea nitrogen (BUN) and creatinine and attenuates renal oxidative stress and tubular pathological injury and apoptosis; further research demonstrated that HP could inhibit the overproduction of proinflammatory cytokines and regulate caspase and BCL-2 family proteins. HP also reduced renal infiltration of macrophages and neutrophils, and its effect might be by downregulating phosphorylation of ERK1/2 and stat3 signaling pathway. Conclusions. This present study suggests that HP could ameliorate cisplatin induced kidney damage by antioxidation and suppressing renal inflammation and tubular cell apoptosis.

Effects of Exercises of Different Intensity on Oxidative Stress and Adiponectin/Adiponectin Receptors of Livers in Obese Rats / 中国运动医学杂志

Objective To discuss effects of three different-intensity exercise on oxidative stress and adiponectin/adiponectin receptor1/2 of the liver in obese rats.Methods Thirty-two Sprague-Dawley rats were fed high-lipid fodder and became the obesity model after 16 weeks.Then they were randomly divided into a high-lipid control group (HF),a low-intensity exercise group (HS),a moderate-intensity exercise group (HM) and an exercise group with progressive intensity (HI),each of 8.Another 8 rats were chosen into a normal control group (NC).The speed of treadmill running of group HS and HM was 10m/min and 15m/min respectively,while that of group HI was10m/min for 20 min,followed by another 20min at and still another 20min at 28～30m/min,five days a week for 6 weeks.Six weeks later,the weight,alanine transaminase (ALT),aspartate transaminase (AST),superoxide dismutase (SOD),malondialdehyde (MDA),tumor necrosis factor alpha (TNF-α),interleukin-6 (IL-6),adiponectin receptors1/2,adiponectin,triglyceride (TG),cholesterol (TC),high-density lipoproteincholesterol (HDL-C),low-density lipoproteincholesterol (LDL-C) and free fatty acid (FFA) were tested.Results Compared with group NC,significant increase was observed in the average weight,TG,TC,LDL-C,FFA,ALT,AST,MDA,TNF-α and IL-6 (P＜0.05 or P＜0.01),while significant decrease was found in the average HDL-C,SOD,adiponectin and adiponectin receptors1/2 of group HF (P＜0.05 or P＜0.01).Compared with group HF,there was significant decrease in the average weight,TG,LDL-C,FFA,ALT,MDA,TNF-α and IL-6 (P＜0.05 or P＜0.01),but significant increase in the average SOD,adiponectin,AR1 and AR2 of group HS,HM and HI (P＜0.05 or P＜0.01),and only HDL-C of group HM increased significantly(P＜0.05).Compared with group HS and HI,significant decrease was found in the average FFA and MDA (P＜0.05),while significant increase was found in the average adiponectin and AR2 of group HM (P＜0.05).Conclusion Aerobic exercise can improve abnormal hepatic lipid metabolism and oxidative stress,strengthen free radical scavenging capacity,prevent liver cell inflammation injury and ameliorate liver metabolism disorder of obese rats induced by high-lipid fodder.Moreover,the effect of moderate-intensity exercise is superior to low-intensity exercise or exercise with progressive intensity,whose mechanism may be related to further activating liver adiponectin receptor 2 through increasing serum adiponectin.

Effects of health education on the mental health and life quality of people at high risk of stroke / 中华物理医学与康复杂志

Objective To observe the effect of health education on the mental health and life quality of people at high risk of stroke.Methods Totally 3092 residents of Wuhan aged over 40 were screened for stroke risk.Of those,392 cases were assessed as at high risk of stroke and were chosen as the study's subjects.They were given a 1-year course of standard health education.Before and after the intervention,their diet,exercise,compliance with medication and smoking habits were recorded.They were also assessed using the self-rating depression scale (SDS),the self-rating anxiety scale (SAS) and the Spitzer quality of life index (QLI).Results Significant improvement in healthy behavior was observed after the intervention.The average SDS score and SAS score had decreased significantly,and the average QLI score was significantly higher than before the intervention.Conclusion Health education can improve the healthy behavior,mental state and life quality of people at high risk of stroke.

The roles of NOD1 and NOD2 in tumorigenesis and development / 中国生化药物杂志

Theinnate immunity system of human body has more and more attention for its antibacterial, antiviral, maintainingimmunehemostasis and promoting tissue damage and repair and other physiological functions.As members of NOD-like receptors(NLRs), NOD1 and NOD2 receptors are identified as intracellular pattern recognition receptors(PRRs), can be identified with molecular damage endogenous(damage-associated molecular patterns, DAMPs)and exogenous injury-molecular pathogen associated molecular(pathogen-associated molecular patterns, PAMPs), and initiation of innate and specific immune response, maintain the steady balance of body.Recently, a bunch of evidence have demonstrated that the importance of NOD1 receptor and NOD2 receptor is not limited in field of anti-infection, and the insulin resistance, kidney and liver damage recovery, cardiovascular disease and tumorigenesis are also closely related with these two receptors.So the aim of this article is to interpret the NOD1 and NOD2 general structure and function, and summarize the link between these two PRRs and tumorigenesis and finally make a clue for cancer immunotherapy.

The clinical value and significance of thyroid hormone changes in patients with acute cerebral infarction / 中华地方病学杂志

Objective To observe the thyroid hormone (TH) changes in patients with acute cerebral infarction in acute phase and convalescence,and to explore its clinical value.Methods Fifty cases of acute cerebral infarction patients from March 2015 to May 2016 in Heilongjiang Provincial Hospital were selected as observation group,at the same time 30 cases of healthy check-up people as control group.Serum levels of triiodothyronine (T3),thyroxine (T4),free triiodothyronine (FT3),free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured in 50 cases of acute cerebral infarction patients on the 2nd day (acute phase) and the 14th day (recovery) after onset of the disease,by using chemiluminescence method,and 30 cases of people underwent healthy physical check-up were treated the same way.Neurological injury and recovery of patients with cerebral infarction were evaluated using NIHSS.According to the recovery level of FT3,patients with cerebral infarction were divided into low FT3 group (FT3 ＜ 3.10 pmol/L) and normal FT3 group (FT3 ≥ 3.10 pmol/L).Prognosis of the patients was judged according to the NIHSS scores 90 days after discharged from the hospital,and NIHSS score improving acuity of 2 was judged as good prognosis.Results The T3 and FT3 levels in patients with acute cerebral infarction were significantly lower than those of people underwent healthy physical examination,the differences were statistically significant [(0.68 ± 0.22) vs(1.82 ± 0.31) nmol/L,(2.08 ± 0.31) vs (4.19 ± 0.75) pmol/L,all P ＜ 0.05].The T4,FT4 and TSH levels in patients with acute cerebral infarction were increased significantly,the differences were statistically significant [(142.56 ± 20.78) vs (109.89 ± 12.37) nmol/L,(12.88 ± 1.15) vs (9.77 ± 0.96) pmol/L,(5.15 ± 1.16) vs (2.95 ± 1.31) mU/L,all P ＜ 0.05].Compared with the acute phase,convalescence of cerebral infarction patients' serum T3 and FT3 levels [(1.75 ± 0.19) nmol/L,(3.97 ± 0.61) pmol/L] increased significantly,the differences were statistically significant (all P ＜ 0.05),and T4,FT4 and TSH [(115.64 ± 14.38) nmol/L,(10.05 ± 1.02) pmol/L,(3.16 ± 0.98) mU/L] obviously decreased,the differences were statistically significant (all P ＜ 0.05).Compared with control group,convalescence of cerebral infarction patients' serum T3,T4,FT3,FT4 and TSH were not statistically different (all P ＞ 0.05).There was a negative correlation between FT3 levels and NIHSS scores on admission (r =-0.586,P ＜ 0.05).Ninety days after discharge,7 cases (38.89％) of the patients had a good prognosis in low FT3 group,and normal FT3 group had 22 cases (68.75％) of patients with good prognosis,and the difference was statistically significant (x2 =7.186,P ＜ 0.05).Conclusions The thyroid hormone has a protective stress reaction in patients with acute cerebral infarction.The thyroid hormone level has changed significantly in the acute phase,and returned to normal level with improvement of the patients.As a biochemical indicator thyroid hormone detection can be used to estimate the prognosis of patients with acute cerebral infarction.

Effect of different stimulants on the LAG3 expression and function of spleen lymphocytes in mice / 中国生化药物杂志

Objective To investigate the effect of different stimulants on the LAG3 expression and function of spleen lymphocytes in mice. Methods The spleen lymphocytes from mice were isolated by density centrifugation.The LAG3 expressions in T cell subsets after exposure to conA, PMA, PHA or anti-CD3/28 antibodies for 24 h or 72 h were analyzed by Flow cytometry.The IFN-γsecretions of conditional medium were detected by ELISA kit.The proliferation of lymphocytes was examined by MTT analysis.Results Treatment with conA for 24 h or 72 h dose-dependently increased LAG3 +CD3 +and LAG3 +CD4 +CD3 +T cell percentages.Similarly, an exposure of anti-CD3/28 antibodies for 72 h significantly increased LAG3 +CD3 +and LAG3 +CD4 +CD3 + T cell percentages.Meanwhile, conA and anti-CD3/28 antibodies increased the IFN-γsecretion of lymphocytes in a time-dependent manner.Furthermore, Treatment with conA, PMA, PHA or anti-CD3/28 antibodies for 72 h could enhance the proliferation of lymphocyte. Conclusion conA and anti-CD3/28 antibodies are effective activators of T cells, and both of them could promote the expression of LAG3 and IFN-γsecretion of lymphocytes.

Establishment of malignant pleural effusion model of Lewis lung cancer based on Micro Echo Technology / 中国生化药物杂志

Objective To establish a malignant pleural effusion model of Lewis lung cancer in C57BL/6 mice based on Micro Echo technology. Methods Single tumor cell suspension of Lewis lung cancer was injected into thoracic cavity.The pleural effusion was detected by Micro Echo technology.The volumes of effusion were quantified and the tumor cells were counted.Results After implanted of tumor cell, malignant pleural effusion can be detected by Micro Echo technology and observed after autopsy.Chemotherapy drugs such as Cyclophosphamide and Cisplatin can decrease the effusion volumes.Conclusion Pleural effusion model of Lewis lung cancer based on Micro Echo technology can be used to evaluate the efficacy of antitumor drugs.

Development of the high-throughput screening fluorescence polarization assay for HSP90 inhibitor / 中国生化药物杂志

Objective To establish the high-throughput screening fluorescence polarization assay for HSP90 inhibitor.Methods E.coli strain BL21 ( DE3) competent cells were transformed with pET24α( +)-HSP90αplasmid.The cell lysate supernatant was induced to product the soluble protein and purified with Ni-NTA agarose.Western blot analysis was used to identify whether the purified protein is HSP90α.The fluorescence polarization assay for screening HSP90 inhibitors was established and optimized using varying concentrations of recombinant HSP90 protein and molecular probe VER00051001.Meanwhile, the binding activity of GA and NVP-AUY922 for HSP90αwas measured by fluorescence polarization assay.Results HSP90αwas induced expression and purified successfully.The fluorescence polarization assay was performed using 80 nM probe VER00051001 and 2.01μg/mL HSP90α, with the Z factor of 0.83.GA and NVP-AUY922 competed with the probes VER00051001 for binding sites of HSP90, with IC50 of 55 nM and 13 nM, respectively.Conclusion A reliable model was established using fluorescence polarization assay for screening HSP90 inhibitors.