The silent cerebral infarct is an clinic symptom that is so slight or transitory as to be easily neglected. There are only neural symptoms and signs,but irresponsible infarct focus can be seen on image. The risk factors of silent cerebral infarct may be the same as those of symptomatic cerebral infarct. Such infarct is likely to influence the course, clinic symptom and prognosis of acute cerebral infarct and may foretell symptomatic cerebral infarct and deteriorate into pseudo-global paralysis or multi-infarcted dementia. Therefore elder who suffer from hypertension or diabetes and experience vertigo, headache, language barrier but without apparent signs and symptoms should receive cerebral CT or MRI. Minor or third-degree precautionary measures can be taken as a chief therapy for cerebral infarct. Alternatively vitamines B_6,B_(12) and folic acid can be supplied to reduce the chance of hyperhomocysteinemia. Headache is the initial symptom in silent brain infarct. Magnesium is effective when dehydration does not work.

Objective To investigate the effect of extracorporeal membrane oxygenation (ECMO) combined with ultrafiltration in treatment of kidney injury induced by serious hemorrhagic shock in rabbits.Methods Models of pressure-controlled hemorrhagic shock was developed in 24 New Zealand white rabbits which were divided into unresuscitation group (n =8),ECMO combined with ultrafiltration group (combined resuscitation group,n =8),and fluid resuscitation group (n =8) according to the random number table.Heart rate was monitored via electrocardiograph and arterial pressure via fermoral artery catheter.Blood samples were collected pre-and post-shock and after resuscitation to measure levels of lactic acid,serum creatinine,IL-6,and TNF-α.Kidney samples were collected for measurement of histopathological changes via HE staining,expression of heat shock protein 70 (HSP70) via immunohistochemical staining.Results Arterial pressure was (53.1 ± 11.4) mmHg in combined resuscitation group,higher than (41.3 ± 11.1) mmHg in fluid resuscitation group and (25.9 ± 10.5) mmHg in unresuscitation group (F =41.425,P ＜ 0.05).Hemorrhagic shock induced significant up-regulation of lactic acid,serum creatinine,IL-6,and TNF-α(P ＜ 0.05),but all were lowered after resuscitation,especially in combined resuscitation group (P ＜ 0.05).HE staining showed the degree of kidney tissue necrosis and inflammatory cytokine infiltration in combined resuscitation group alleviated notably compared with fluid resuscitation group.Median and interquartile values of HSP70 were 17 828.960 0 (15 779.865 0-21 751.980 0) in unresuscitation group,2 714.270 0 (1 339.215 0-7 616.950 0) in fluid resuscitation group,and 262.930 0 (198.820 0-538.195 0) in combine resuscitation group,with statistical differences among groups(P ＜ 0.05).Conclusion ECMO combined with ultrafiltration is superior to conventional fluid resuscitation in improving hypoxia tissue injury and inflammatory reaction after hemorrhagic shock and is beneficial to attenuating kidney injury.

Objective To evaluate the efficacy and safety of recombinant adenovirus-p53 (rhAd-p53) combined with neoadjuvant chemotherapy in treatment of locally advanced cervical cancer.Methods Forty patients with stage Ⅰ R2-Ⅲ A locally advanced cervical cancer were randomly divided into 2 groups,gene therapy + neoadjuvant chemotherapy group (rhAd-p53+PVB group,n =20.They received one course of chemotherapy consisting of PVB.rhAd-p53 solution 1 ×1012 VP was injected intratumorally every three days for three circles since the 3rd day of PVB chemotherapy) and chemotherapy group (PVB group,n=20,the above course of chemotherapy was conducted).The volums of tumors was observed.Patients were monitored for adverse event.The expression of VEGF,p53 pertein and MVD in tumor tissue was detected by immunohistochemistry.Results The evaluation was performed three weeks after the completion of chemotherapy.The PVB group response rate (CR+PR) was 75 ％,while the effective rate was 95 ％ of the PVB combined with gene group.After using of the PVB chemotherapy,the tumor was shrunk by (11.42±2.78) cm2.However,the volums of tumor were significantly shrunk by (15.25±4.00) cm2 using the PVB combined with gene therapy,and P ＜ 0.05.The positive expression rate of VEGF,p53 protein and MVD were reduced respectively in PVB group and rhAd-p53 + PVB group with statistic significance.There were no additional adverse events by recombinant adenovirus-p53 combined with neoadjuvant chemotherapy.Conclusion A potentially gene therapeutic agent for cervical cancer treatment,intratumoral injection of rhAd-p53 is effective.

Taking guizhi fuling capsule (GZFL) for instance, a new method about reference Chinese medicine preparation which was used as standard substance for the quality evaluation of complex Chinese medicine preparation by the fingerprint of reference preparation instead of standard fingerprint was proposed. It could eliminate the errors from different instruments, chromatographic columns and solve the problem of similarity matching in the absence of standard fingerprint. The qualification of reference GZFL was evaluated according to the quality control method of GZFL from Chinese Pharmacopoeia. Then multiple batches of GZFL were estimated, taking fingerprint of reference preparation and standard fingerprint as references, respectively, at different instruments and chromatographic columns. Finally, the packaging and expiration date for reference GZFL were confirmed according to the results of stability investigation. The results indicated that the fingerprint of reference GZFL could be used to assess the quality of GZFL better than standard fingerprint. The data of accelerated stability and long-term stability test demonstrated that reference GZFL was stable in the conditions of double blister package. Therefore, reference GZFL can be used as standard substance in quality control of GZFL.
Capsules ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; standards ; Reference Standards

Carcinoma, Hepatocellular ; genetics ; DNA Methylation ; DNA-Binding Proteins ; genetics ; Histone-Lysine N-Methyltransferase ; Humans ; Liver Neoplasms ; genetics ; Nuclear Proteins ; genetics ; Promoter Regions, Genetic ; genetics ; Transcription Factors ; genetics

OBJECTIVETo reverse the multidrug resistant (MDR) phenotype of human breast carcinoma cells by small hairpin RNA (shRNA) technique targeting hypoxia-inducible factor (HIF)-1alpha gene.

METHODSSmall hairpin RNA (shRNA) eukaryotic expression vector targeting HIF-1alpha gene, named pSilencer-HIF, was constructed and transfected into MCF-7/ADR human breast cancer cells by liposome technique. Tumor cell livability (TCL) and Rhodamine 123 efflux assay were used to monitor the biological changes of the transfected cells. The mRNA and protein expression of HIF-1alpha and mdr-1 were investigated by RT-PCR and Western blot.

RESULTSThe successful construction of pSilencer-HIF plasmid was confirmed by DNA sequencing. HIF-1alpha mRNA and protein levels were significantly decreased in MCF-7/ADR cells after the transfection and there was a direct correlation between HIF-1alpha and mdr-1 expression. By comparing the cells transfected with control vector and the MCF-7/ADR cells transfected with pSilencer-HIF, a reduced TCL from 76% to 43%, and an increased Rhodamine 123 fluorescence intensity from 22.0% to 86.6% were observed.

CONCLUSIONSpSilencer-HIF-1alpha has been successfully constructed. The inhibition of HIF-1alpha expression through shRNA technique can significantly reverse the multidrug resistance phenotype of MCF-7/ADR cells.

Breast Neoplasms ; pathology ; Cell Line, Tumor ; Drug Resistance, Multiple ; drug effects ; physiology ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; RNA Interference ; RNA, Small Interfering ; pharmacology

To observe the expression of drebrin in the distal cerebrospinal fluid contacting neurons (dCSF-CNs) of rats with chronic constriction injury (CCI) of sciatic nerve by immunofluorescence technique, male Sprague-Dawley rats were randomly divided into three groups: control group, sham surgery group and CCI group. The behavior of rats was scored. After choleratoxin subunit B-conjugated horseradish peroxidase (CB-HRP, 3 muL) was injected into the lateral cerebroventricle to trace dCSF-CNs, the expression of drebrin was observed in the dCSF-CNs through immunofluorescence double staining and laser scanning confocal microscopy technique. The results showed that only the pain threshold of CCI group was decreased. The dCSF-CNs were clearly displayed in three groups. No drebrin expression was observed in the control and sham groups. In CCI group, drebrin was markedly expressed in intracytoplasm. It is suggested that the technique displaying dCSF-CNs with immunofluorescence is successful and the dCSF-CNs are possibly involved in the transmission of nociceptive information under the neuropathic pain state.
Animals ; Cerebrospinal Fluid ; Constriction, Pathologic ; Male ; Neuralgia ; metabolism ; Neurons ; metabolism ; Neuropeptides ; metabolism ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries

China ; Humans ; Maximum Allowable Concentration ; Occupational Exposure ; prevention & control

Objective: To investigate the anti-inflammatory effect of hesperetin (HSP) on lung damage induced by paraquat (PQ) in rats by detecting the levels of inflammatory makers in rat lung tissues. Methods: 140 Wistar male rats were randomly divided into negative control group, HSP control group, HSP control group, paraquat model group, pirfenidone (PDF) positive control group, and 100, 200, 400 mg/kg HSP treatment groups. All groups were exposed to 50mg/kg paraquat by oral gavage except for the negative control group and HSP control group. After 24 hours, the rats in each group were given drug intervention once daily. 10 rats were randomly sacrificed at 7th day and 28th day after exposure to paraquat respectively. 3 rats were randomly selected from them and HE, Masson staining were used to observe the pathological changes in the lungs of each group. Each group randomly selected 6 rats at two time points to detect the levels of TGF-β₁, TNF-α, IL-4, IL-10, IL-1β and IFN-γ in rat lung tissues. Results: Histopathological examination found that the lung injury were reduced in the rats of PDF positive control group and all HSP treatment groups. Compared with the negative control group, the levels of TGF-β1, IL-1β, TNF-α, IL-4, and IL-10 in rat lung tissues were significantly increased (P<0.05, P<0.01) after PQ exposure at two points in time, and there was no significant difference in the level of IFN-γ in lung tissues compared with the negative control group (P>0.05) . The levels of TGF-β1, IL-1β, IL-4, IL-10 and TNF-α in the lung tissues of rats on the 7th day in different dose treatment groups of HSP were reduced compared with those in the PQ model group with varying degrees (P<0.05, P<0.01) . The level of IFN-γ in lung tissues of rats were not significantly different from that of model group (P>0.05) . The levels of TGF-β₁ and TNF-α in lung tissue of rats on the 28th day in PDF positive control group and different dose treatment groups of HSP were reduced compared with those in the PQ model group with varying degrees (P<0.05, P<0.01). The levels of IFN-γ in the rat lung tissues were increased compared with those in the PQ model group (P<0.05). Besides, there were no significant in the levels of IL-1β, IL-4 and IL-10 in lung tissues compared with PQ model group (P>0.05). Conclusion HSP can reduce lung damage induced by PQ in rats by inhibiting the release of inflammatory factors and promoting the secretion of anti-inflammatory factors.

The study was purposed to investigate the expression and function of non-muscle myosin heavy chain-IIA (NMMHC-IIA) in Fechtner syndrome in order to explore the pathologic changes of kindy disease and the mechanism of granulocyte inclusion body formation. NMMHC-IIA levels in granulocytes were analyzed by Western-blot, the expressions of NMMHC-IIA, IIB in HEK-293 cells were detected by RT-PCR and were analyzed by co-immunoprecipitation. The results indicated that the IIA/beta-actin ratio for Fechtner syndrome granulocytes was (0.35 +/- 0.12), and obviously decreased as compared with that of normal control (0.87 +/- 0.18) (p < 0.01). The IIA and IIB expressed higher in HEK-293 cells. The interaction of IIA and IIB was confirmed by co-immunoprecipitation in HEK-293 cells. It is concluded that dominant-negative effect of NMMHC-IIA is involved in the formation of inclusion bodies. IIA and IIB show obvious interaction, IIB partly compensates the IIA defect derived from MYH9 mutations, and may delay or prevent the development of clinically relevant abnormalities.
Blood Platelet Disorders ; genetics ; metabolism ; pathology ; Cell Line ; Granulocytes ; pathology ; Humans ; Inclusion Bodies ; pathology ; Kidney ; cytology ; embryology ; metabolism ; Mutation ; Nonmuscle Myosin Type IIA ; genetics ; metabolism ; physiology ; Nonmuscle Myosin Type IIB ; genetics ; metabolism ; physiology ; Syndrome ; Thrombocytopenia ; genetics ; metabolism ; pathology