Objective Zika virus disease is an acute infectious disease caused by Zika virus transmitted through Aedes mosquitoes. To explore the therapeutic effect of integrated traditional Chinese and Western Medicine for Zika virus disease, the treatment process of the first imported case in China was reviewed. Methods The first imported Zika virus disease in China was admitted to Ganxian People's Hospital in Jiangxi Province on February 6th, 2016, and the patient received isolation treatment for 9 days and cured later. The effect of antiviral treatments including Xiyanping injection was evaluated based on clinical diagnosis and treatment process of the patient. Results A 34-year old male patient was admitted with chief complaint of fever for 9 days, orbital pain and itching rash for 4 days on February 6th, 2016. ① Epidemiological characteristics: the patient was bitted by mosquitoes during his business trip in Venezuela since January 1st, where Zika virus disease was spreading. On January 20th he had dizziness without fever, and the symptom disappeared after taking medicines without details. Paroxysmal dizziness, chills and mild fever without myalgia was experienced on January 28th. On February 3rd small red rash appeared in the neck, spreading to anterior part of chest, limbs and trunk, and the fever, fatigue, nausea was continued, and a new symptom of paroxysmal pain in back of ears and orbits appeared, during which he had not go to hospital. The symptoms relieved on February 4th. He returned to Ganxian County on February 5th, he had yellow stool 3 times with normal temperature, without abdominal pain, and red rash still appeared in the neck. He went to Ganxian People's Hospital on February 6th, 2016. ② Clinical manifestation: the vital signs showed a temperature of 36.8 ℃, a pulse rate of 80 bpm, a respiratory rate of 20 bpm, and a blood pressure of 110/70 mmHg (1 mmHg = 0.133 kPa). It was showed by physical examination that red rash appeared in the neck, and no superficial enlarged lymph nodes were found. Bilateral conjunctival congestion was obvious, physiological reflex existed and pathological reflex was not found. ③ Auxiliary lab test and examination: no abnormal finding were revealed throughout examination and laboratory tests, including routine blood test, liver function, renal function, serum myocardial enzyme, electrolyte, blood sugar, C-reactive protein (CRP), troponin I (TnI), and procalcitonin (PCT), except slight prolongation in activated partial thromboplastin time (APTT, 38.6 s) on February 6th; and slightly dense shadow in left lung in lung CT scan, considering inflammatory changes and slight emphysema (especially in the left lower lung) as well as bilateral renal calculus on February 8th. No significant abnormalities were found in electrocardiogram and B ultrasound test of liver, spleen, and pancreas. ④ Virus confirmation: Zika virus nucleic acid was positive reported by Jiangxi Province Center for Disease Control and Prevention (CDC) on February 7th and Chinese CDC on February 9th, respectively, though Dengue virus were negative reported by Ganzhou CDC on February 6th. Right after the first diagnosis, anyone who had been in close contact with the patient received medical monitoring. ⑤Treatment process: on February 6th, symptomatic treatment was prescribed since admitted into the infectious isolation wards and daily intravenous drip of Xiyanping injection 250 mg was prescribed for antiviral therapy. On February 7th, the patient had no fever, with occasional chills, neck rash was disappeared, orbital pain relieved and bilateral conjunctival hyperemia range was paler and narrowed, and his condition improved. Ibuprofen was administered for defervesce 3 times a day when his temperature reached to 37.5 ℃ at 16:00. On February 8th, the patient had no fever, times of chills was significantly reduced, without myalgia and rash, orbital pain and conjunctival hyperemia further recovered. On February 9th, bilateral eyes slightly tingling, mild conjunctival congestion, no fever chills or other discomfort was found. The chloramphenicol eye drops was prescribed for relieving sting pain with conjunctival congestion twice a day as recombinant human interferon alpha eye drops was out of store. The patient was comfortable from February 11th to February 13th. Blood and urine test for Zika were reported negative by the Chinese CDC and Jiangxi Province CDC. Because all the discharge criteria were satisfied, the patient was discharged on February 14th. Conclusions At present, there is no specific effective drug to prevent and treat Zika virus disease effectually. After receiving symptomatic treatment and antiviral treatments including Xiyanping injection, the patient's symptoms were relieved. Zika virus nucleic acid in blood and urine was negative. The patient was discharged. Combination of traditional Chinese medicine and Western medicine maybe a good method to prevent and treat Zika virus disease.

Objective To investigate the effects of acetylated HMGB1 on cognitive function in rats with sepsis associated encephalopathy (SAE) and the effect of HMGB1 inhibitor.Methods Forty-eight males mice were randomly assigned to three groups (n=16): sham group (group S),cecal ligation puncture group (group C),cecal ligation puncture+sodium butyrate group (group B).Cecal ligation puncture was applied to establish the SAE model,and group S received sham operation.Rats in groups S and C were injected with normal saline 5 ml/kg 30 min and 4 h after CLP,respectively.The rats in group B were intraperitoneally injected with sodium butyrate 500 mg/kg 0.5 h and 4 h after CLP,respectively.All animals were performed Morris water maze test on 4th day after operation,and the exploring time of space exploration experiments were assessed on 7th day after CLP surgery.IL-6,BDNF,HMGB1 and acetylated HMGB1 expression in hippocampus of all rats were determined by Western Blot.Results Compared with group S,the latency of rats in group C was longer and the exploring time was shorter (P<0.05).Compared with group C,the latency of rats in group B was shorter and the exploring time was longer (P<0.05).Compared with group S,the expression of IL-6,HMGB1 and acetylated HMGB1 in group C increased (P<0.05) and the level of BDNF decreased (P<0.05).Compared with group C,the expression of IL-6,HMGB1 and acetylated HMGB1 in group B decreased (P<0.05) and the level of BDNF increased (P<0.05).Conclusion HMGB1 inhibitor sodium butyrate can inhibit the expression of acetylated HMGB1 in the hippocampus of SAE rats,and reduce the cognitive impairment induced by sepsis.

Objective To study the cytotoxicity against brain microvessel endothelial cells and blood compatibility in rats of OX26 conjugated endomorphin (EM) loaded hyperbranched polyglycerols-poly(lactic-co-glycolic acid)(HBPG-PLGA) nanoparticles.Methods Prepared nanoparticles were divided into group B (HBPG-PLGA nanoparticles),group EP (EM-HBPG-PLGA nanoparticles) and group OEP (OX26-EM-HBPG-PLGA nanoparticles).The cytotoxicity against brain microvessel endothelial cells (BMECs) of nanoparticles of different groups were measured by MTT test,haemolysis test,normal haemotological parameter and several primary items of coagulation system were tested after nanoparticles of different groups and different dosages injection on rats.Results ①All the three groups of nanoparticles induced decreased cell viability in a dose dependent manner in MTT test,whereas all groups of nanoparticles showed low cytotoxicity against the BMECs during 30 to 600 μg/ml.②There was no significant difference in haemolysis ratio (P＞0.05) and normal haemotological parameter (P＞0.05).③There was no significant difference between the low dosage of all the three groups of nanoparticles and the control group on the function of coagulation system in rats (P＞0.05).④Compared with C group,high dose groups demonstrated longer prothrombin time (PT),activeated partial thromboplasting time (APTT) and lower fibrinogen (Fbg) (P＜0.05).At the same time,compared with the low dose subgroups,PT and APTT were prolonged,Fbg significantly decreased in the high dose subgroups (P＜0.05 or P＜0.01).Conclusion OX26 coupled with EM-HBPG-PLGA nanoparticles showed low cytotoxicity against BMECs and had no significant effect on the coagulation system in rats with low concentration and low dosage.

Objective To prepare a novel brain active-targeting endomorphin (EM) loaded hyperbranched polyglycerols-poly (lactic-co-glycolic acid) (HBPG-PLGA) nanoparticles (NPs) and study its mechanism of passing across blood brain barrier (BBB) in brain microvascular endothelial cells (BMEC).Methods The OX26 (transferring receptor monoclonal antibody) conjugated EM loaded HBPG-PLGA NPs was constructed according to water-in-oil-in-water emulation solvent evaporation technique as a novel biodegradable brain active-targeting drug delivery system.The properties of the NPs were evaluated by transmission electron microscope (TEM) in vitro.Through flow cytometry and laser scanning confocal microscope,the mechanism of passing across BBB was evaluated.Results The preparation methodology of NPs was optimized and established.The mean diameter was (170±20) nm and Zeta potential was about-27 mV.Core-shell construction was showed on TEM.Cellular uptake study showed that the uptake of NPs was via a caveolae-mediated endocytic pathway,then endomorphin and carrier were divided into two parts in BMEC.Conclusions The OX26 conjugated EM loaded NPs were stable,and demonstrate remarkable effects on crossing BBB.Cellular uptake by BMEC is a very important mechanism of the NPs' brain activating-targeting effect.

Objective To investigate the role of hippocampal cyclophilin D (CypD) in sepsis-associated encephalopathy in rats.Methods A total of 36 adult male Sprague-Dawley rats,aged 3-4 months,weighing 300-400 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis + CypD inhibitor cyclosporin A group (CsA group).Sepsis was induced by cecal ligation and puncture (CLP).Cyclosporin A 6 mg/kg was injected intraperitoneally at 30 min before CLP in group CsA.All the animals underwent Morris water maze test on 4th day after CLP.The animals were sacrificed after the test,and the hippocampus was isolated for determination of the expression of cytochrome c (Cyt c),CypD,caspase-3,brain-derived neurotrophic factor (BDNF),phosphorylated protein kinase A (p-PKA),and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB).Results Compared with group Sham,the escape latency was significantly prolonged,the space exploration time was shortened,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was up-regulated,and the expression of BDNF was down-regulated in S and CsA groups (P＜0.05).Compared with group S,the escape latency was significantly shortened,the space exploration time was prolonged,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was down-regulated,and the expression of BDNF was up-regulated in group CsA (P＜0.05).Conclusion Hippocampal CypD may be involved in the pathophysiological mechanism of sepsis-associated encephalopathy,and the downstream mechanism is probably related to promotion of activation of PKA/CREB signaling pathway in rats.

Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

BACKGROUND: Acetabular malignant tumor reconstruction is to obtain pelvic stability and lower limb walking function to excise the tumor at safe margin.Excision range has been evaluated by MRI,CT,X-ray,which are subjective and lack preoperative design.Computer-aided three-dimensional reconstruction can evaluate tumor erosion range from all planes to accurately excise the tumor.OBJECTIVE: To evaluate the value of computer aided design in the treatment of acetabular malignant tumor.METHODS: One case with acetabular hemangiosarcoma was checked with lamellar CT scanning,which acquired some two-dimensional data in disease area.The three-dimensional reconstruction of anatomical model,design of cutting bone extent,design of individual prosthesis and sham operation were made by computer.Based on computer aided design proposal,acetabular tumor was resected,pelvic ring and right hip articulation were reconstructed with allogeneic semi-pelvis and individual total hip replacement.RESULTS AND CONCLUSION: The patient began to non-weight bearing walk with double crutches 2 months after operation.At6 months,the patient walked normally.The right hip joint motion was good with no pain.Postoperative X-ray film displayed individual prosthesis matched to pelvis.The patient fell a little numbness of skin in the lateral of right hip.No phlebothrombosis,prosthesis loosening or dislocation was found.Computer aided design has a good perspective of application in the treatment of acetabular malignant tumor.Individualized treatment can improve operation accuracy,reliability,convenience and curative effect.

Objective To investigate the curative effect of granulated cancellous bone autograft in treatment of refractory bone nonunion after limited contouring of bone ends. Methods Between 2003 and 2006, 13 patients with refractory bone nonunion were treated with external fixation and granulated cancellous bone autograft after limited contouring of bone ends. Results The mean follow-up period was 22.6 months (19-30 months), which showed that all patients gained bone union and resumed com-plete weight loading or previous job at final follow-up. The mean fixation time of external fixators was 10.6 months (7-18 months). The intermittent or persistent pin-track infection occurred in eight patients and relieved by pin-track care and oral or parenteral antibiotics, with no infection after removing external fixator. Conclusion The granulated cancellous bone autograft after limited contouring of bone ends is an effective method for treatment of refractory bone nonunion.

Objective To investigate the change of the basic fibroblast growth factor(bFGF) leve in human detrusor muscle(DM)in bladder outlet obstruction(BOO)due to benign prostatic hyperplasia(BPH)and its implication.Methods Fifty-four patients with BPH were divided into two groups:the obstructive DM stability and instability groups;and 15 men with bladder tumor who underwent operation in the same period were enrolled in the control group.The bFGF mRNA level in DM was measured by reverse transcription and polymerase chain reaction(RT-PCR)and the bFGF protein level was measured by immunohistochemical staining method.Results The bFGF-mRNA expression level of bladder smooth muscle cells was significantly lower in the control group than that in the obstructive DM stability and instability groups(all P＜0.05),but there was no significant difference between the obstructive DM stability and instability groups(P＞0.05). Conclusions The expression level of bFGF mRNA in bladder DM is elevated in BOO due to BPH,but there is little or no correlation between the increased expression of bFGF mRNA and detrusor muscle instability.

OBJECTIVETo study the correlation of polymorphisms of CYP1A1 MSPI and glutathiones S-transferase (GST-M1) independently and in combination with the risk of lung cancer.

METHODSA case control study which included 91 cases of lung cancer and 138 controls collected from the First Affiliated Hospital of Sun Yat-sen University of Medical Sciences, Guangzhou Tumor Hospital and The Red Cross Hospital of Guangzhou or conmunity area. All subjects were investigated with a uniform questionnaire. Blood samples were collected from all cases and controls for detecting CYP1A1 MSPI and GST-M1 polymorphisms which were analyzed by PCR and RFLP.

RESULTSIt showed that there was no significant difference in frequencies of this genotypes of CYP1A1 MSPI between the two groups. The frequency of GST-M1 null (0/0) genotype was higher in the case group than in the control group, with an OR of 1.38 (95% CI 0.81 - 2.38), but there was no statistical significance. However, combination of several genotypes was strongly associated with lung cancer. There was a synergistic interaction between the m2m2 genotype of CYP1A1 MSPI and GST-M1 (0/0) genotype, with an OR of 2.47 (95% CI 1.03 - 5.90).

CONCLUSIONThe combination of two genetic polymorphisms significantly increases the risk of lung cancer.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Cytochrome P-450 CYP1A1 ; genetics ; Female ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Lung Neoplasms ; etiology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk ; Smoking ; adverse effects