Angiogenesis Inhibitors ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; therapy ; Chemoembolization, Therapeutic ; methods ; Endostatins ; therapeutic use ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; therapy ; Microvessels ; pathology ; Neovascularization, Pathologic ; pathology ; Vascular Endothelial Growth Factors ; metabolism

BACKGROUND:Orthotopic lung transplantation model in a rat is the key to investigate the chronic rejection after lung transplantation. However, the precise surgical technique and difficult operation limit the application of the model. OBJECTIVE:To improve the process of anesthesia and lung transplantation, and to establish a rapid, safe and reversible rat lung transplantation model. METHODS:A total of 42 rats were used to establish the model, including 21 donor models and 21 receptor models. The donor lung was excised by median sternotomy with dissection of the left lung and implantation of cuffs (intravenous catheters cut into 1.5 mm sections). The left lung was implanted in the recipient by lateral thoracotomy using the cuffs for anastomoses. The duration of surgery and success rate of transplantation were recorded and calculated. RESULTS AND CONCLUSION:The survival rate of rats after lung transplantation was 100%. The time of left donor lung extraction was (35.3±5.1) minutes in average. The time of placing cuff in donor lung was (12.5±4.6) minutes in average. The surgical procedure time of recipient was (50.2±3.3) minutes. The time of arteriovenous and bronchus casing anastomosis was (27.7±6.2) minutes. After pulmonary artery and vein blood flow was disparked, the whole lung turned red rapidly, blood perfusion was sufficient, venous returned unimpeded;after mechanical ventilation resumed, al graft lungs expanded wel . This improved anesthesia and lung transplantation technique in rats can provide a valid, reliable and reproducible animal model for studying immune responses and rejection in lung transplantation.

Objective To investigate the effects of δ-opioid receptor agonist DADLE (D-Ala2-D-Leu5-enkephalin) on the hemodynamics and oxygen metabolism in rats with sepsis. Methods Eighty healthy male SD rats were randomly divided into 4 groups ( n = 20 each) : sham operation group (group S), sepsis group (group SEP) ,DADLE, group and DADLE2, group. Sepsis was induced by cecum ligation and puncture (CLP) in SEP, DADLE,and DADLE2 groups. In DADLE1 and DADLE2 groups, 0.5 mg/ml DADLE 10 mg/kg was injected intraperitoneally (IP) 0.5 h before CLP and immediately after CLP respectively. Mean arterial pressure (MAP), left ventricular systolic pressure (LVSP) and ± dp/dtmax were recorded at 0, 2, 4 and 6 h after CLP (T1-4). Blood samples from left common carotid artery and right external jugular vein were collected at T4 for blood gas analysis. The cardiac index (CI), O2 delivery (DO2), O2 consumption (VO2) and O2 extraction rate (ERO2) were calculated.Results Compared with group S, MAP and LVSP were significantly increased at T2, while decreased at T3,4, and ± dp/dtmax was significantly increased in group SEP, MAP was significantly increased at T2, while decreased at T3,4, LVSP was significantly increased at T2,3, while decreased at T4 , and ± dp/dtmax was significantly increased in DADLE, and DADLE2 groups, and CI, DO2 and VO2 were significantly decreased and ERO2 was increased in SEP, DADLE, and DADLE2 groups (P＜0.05). Compared with group SEP, MAP, LVSP and ± dp/dtmax at T3,4 and CI, DO2 and VO2 were significantly increased, while ERO2 was significantly decreased in DADLE1 and DADLE2 groups (P ＜ 0.05). There was no significant difference in the parameters mentioned above between DADLE1 and DADLE2 groups ( P ＞ 0.05). Conclusion δ-opioid receptor agonist DADLE can obviously improve the hemodynamics and oxygen metabolism in septic rats.

Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.

OBJECTIVETo study the advantages of Chinese medicine (CM) in treating insulin resistance and disorders of glucose and lipid metabolism in patients with polycystic ovarian syndrome (PCOS), and to explore its underlying mechanisms.

METHODSOne hundred PCOS patients were assigned to three groups: 40 patients in the CM group treated by CM, 30 in the WM1 group treated by metformin, and 30 in the WM2 group treated by cyproterone. Before treatment and at 3 cycles and 6 cycles after treatment, changes of body mass index (BMI), fasting serum insulin (FINS) and fasting blood sugar (FBG) levels as well as lipid spectrum were measured and the homeostasis model of insulin resistance (HOMA-IR) was calculated. Meanwhile, the recovery of ovulation was observed.

RESULTSThere were 30, 22 and 23 patients in the CM, WM1 and WM2 group respectively completed their 6-month treatments. Levels of FINS, FBG, HOMA-IR, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were lowered and high-density lipoprotein cholesterol (HDL-C) level increased in the CM group after 6-month treatment, showing significant difference as compared with the baseline (P < 0.05), and the difference in comparing with the WM2 group was statistically significant in terms of MBI, FINS, FBG, HOMA-IR, TC and LDL-C (P < 0.05). The ovulation rate was 53.3% (16/30) in the CM group, 27.3% (6/22) in the WM1 group and 21.7% (5/23) in the WM2 group, comparison between them showed a significant difference between the CM group and the WM2 group (P < 0.01).

CONCLUSIONCM is effective for the treatment of PCOS in improving insulin resistance, adjusting blood sugar and lipids levels and recovering ovulation.

Adolescent ; Adult ; Blood Glucose ; metabolism ; Cholesterol, HDL ; blood ; Cyproterone ; therapeutic use ; Drugs, Chinese Herbal ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Metabolic Diseases ; blood ; Metformin ; therapeutic use ; Polycystic Ovary Syndrome ; blood ; drug therapy ; Young Adult

Objective To study the protective effects of DADLE on pulmonary function in rats with sepsis and the mechanism.Methods Seventy-two SD rats were randomly divided into sham operated group(SO),septic group(SEP),and DADLEtreated group (DADLE).Sepsis model was induced by cecal ligation and puncture(CLP).In SO group,the abdomen was opened without any other treatment.In DADLE-treated group,DADLE(0.5 mg/ml) was administerd at a dose of 5 ml/kg by intravenous injection after CLP.Rats were sacrificed at the 2nd,6th and 10th h after CLP.Arterial blood was collected for blood gas analysis.The wet-to-dry lung weight ratio was measured,and the levels of TNF-a and IL-6 in blood were detected.The levels of MPO,MDA and ATP in lung tissue were determined.The pathologic changes of the lungs were examined under a light microscope.Results As compared with SEP group,PaCO_2,and PaO_2 were significantly increased(P<0.05),while the wet-to-dry ratio and levels of serum TNF-a and IL-6 were significantly reduced(P<0.05),and levels of MPO and MDA were significantly reduced(P<0.05) and content of ATP in lung tissue was significantly increased (P<0.05)in DADLE group.More severe pathological changes were found in SEP group than in DADLE group.Conclusion DADLE has pulmonary protective effects in rats with sepsis.

Objective To investigate the effect of δ-opioid receptor agonist D-Ala2-D-Leu5-enkephalin (DADLE) on the celluar immune function in septic rats. Methods One hundred and fifty healthy male SD rats weighing 154-198 g were randomly divided into 3 groups (n = 50 each):group Ⅰ sham operation (group S);group Ⅱ sepsis (group SEP) and group Ⅲ DADLE. Sepsis was induced by cecum ligation and punture (CLP) in group Ⅱ and Ⅲ. In group Ⅲ 0.5 rmg/kg DADLE 10 ml/kg was injected intraperitoneally (IP) immediately after CLP operation. Seven day survival rate was calculated. Blood samples were collected from 10 animals at 4, 8 and 12 h after operation (T1-3) respectively in each group for determination of serum TNF-α and IL-10 concentrations by ELISA and changes in T-cell subsets by flow cytometry. Results CLP significantly increased serum TNF-α and IL-10 concentrations and TNF-α/IL-10 ratio at T1-3 and decreased CD4+ and CD4+/CD8+ ratio and increased CD8+ at T3 in group Ⅱ as compared with group S (group Ⅰ). DADLE treatment significantly attenuated the CLP-induced above changes. Seven-day survival rate was significantly higher in DADLE group than in CLP group.Conclusion δ-opioid receptor agonist DADLE can improve the celluar immune function of rats with sepsis and increase the survival rate.

Objective: To know the pre-treatment drug resistance ( PDR ) status of newly reported human immunodeficiency virus type 1 ( HIV-1 ) infected individuals in Wenzhou, so as to provide guidance for antiretroviral therapy ( ART ). Methods: Totally 232 plasma samples of newly reported HIV-1 infected individuals who had not received ART were collected in Wenzhou in 2019. Virus ( HIV-1 ) RNA was extracted, followed by reverse transcription PCR and nested PCR to amplify the pol region and sequence. Resistance mutations and resistance to non-nucleoside reverse transcriptase inhibitors ( NNRTIs ), nucleoside reverse transcriptase inhibitors ( NRTIs ) and protease inhibitors ( PIs ) was analyzed. Results: The pol region sequences from 199 infected patients were obtained and the incidence of PDR was 8.04% ( 16/199 ). Eight genotypes were detected, including circulating recombinant forms ( CRFs ) CRF07_BC ( 47.24%, 94/199 ) and CRF01_AE ( 29.15%, 58/199 ) which were the dominant types. Two unique recombinant forms ( URFs ) were detected, namely URF( CRF01_AE/BC ) and URF( B/C ) . Thirty-one cases ( 15.58% 31/199 ) had drug-resistant mutations. For NNRTIs, NRTIs and PIs, 20 cases ( 64.52% ) , 2 cases ( 6.45% ) and 9 cases ( 29.03% ) with drug resistance mutations were detected, respectively. The resistance mutations to NNRTIs included K101E, K103N/R, V106I, E138K, V179D/E/T, Y181C, G190A and H221Y. Four cases each had two resistance mutations to NNRTIs. The resistance mutations to NRTIs were V75M and M184V. The resistance mutations to PIs were M46I, L33F and Q58E. For the newly released NNRTI drug Doravirine ( DOR ), two cases were found to have mutations of resistance. Conclusions The incidence of PDR among newly reported HIV-1 patients in Wenzhou is 8.04%, mainly caused by NNRTIs drug-resistant mutation. Resistance to the new drug DOR has emerged. The surveillance of drug resistance should continue to be strengthened.

OBJECTIVENeurogenesis in the dentate gyrus of hippocampus persists in brain of the immature and adult mammalian including human and it can be regulated by physiological and pathological events including nutritional status and seizures. The present study was designed to investigate the potential effects of malnutrition followed by status epileptics on hippocampal neurogenesis in the immature rat.

METHODSRat pups were divided into 4 groups: malnourished (M), nourished (N), malnourished plus seizures (MS) and nourished plus seizures (NS). The rat pups of group M and group MS were maintained on a starvation regimen from postnatal day 2 (P2) to P18. The status epilepticus of the rat pups in group MS and group NS was elicited by unilateral microinfusion of kainic acid (KA) into the amygdula at P15. Rat pups of the 4 groups were given bromodeoxyuridine (BrdU) intraperitoneally twice daily for 2 days beginning at P17. At P19, the rat pups were killed and the brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using early neuron- or glia-specific markers TuJ1 (beta III tubulin) or GFAP (glial fibrillary acidic protein).

RESULTSThere were no significant differences in the latent time of seizure between group M and group N [(12.4 +/- 2.6) min vs. (12.1 +/- 2.9) min, P < 0.05]. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. BrdU-labeled cells were significantly higher in the rats of group MS (374 +/- 18) than group M (303 +/- 20), group NS (312 +/- 24) than group N (269 +/- 18), respectively (P < 0.01). There was also significant difference between group M and group N, group MS and group NS, respectively (P < 0.01). No significant difference was seen between the rats of group NS and group M (P > 0.05). Approximately 60% of BrdU-labeled cells coexpressed TuJ1, and 5% approximately 10% of those co-expressed GFAP.

CONCLUSIONEarly malnutrition do not alter KA seizure susceptibility and the behavioral manifestations of seizures at P15. Although malnutrition and status epilepticus can increase the proliferation of newly developed cells in the immature rat respectively, malnutrition followed by status epilepticus further increases this proliferation. Furthermore, most of newly developed cells differentiate into early neurons.

Animals ; Animals, Newborn ; Body Weight ; Bromodeoxyuridine ; metabolism ; Glial Fibrillary Acidic Protein ; analysis ; Hippocampus ; chemistry ; pathology ; Immunohistochemistry ; Malnutrition ; pathology ; Neurons ; chemistry ; pathology ; Rats ; Rats, Wistar ; Status Epilepticus ; chemically induced ; pathology ; Tubulin ; analysis

OBJECTIVEIdiopathic thrombocytopenic purpura (ITP) is a hemorrhagic disease in children with blood platelets redundant destruction caused by chaotic immunological mechanism. However, some patients with ITP with negative platelet-associated antibody and ineffective adrenal cortical hormone therapy probably have special pathogenesis. It is indicated that the human cytomegalovirus (HCMV) can incubate in haemopoietic stem cell/ancestral cell to inhibit its generation and differentiation. Therefore, the study was designed to investigate HCMV-late mRNA expression in megakaryoblast for the purpose of examining the pathogenesis of ITP and to examine the effectiveness of ganciclovir on ITP.

METHODSColony forming unit-megakaryocyte (CFU-MK) of 46 ITP patients with HCMV infection were incubated. Reverse transcription-polymerase chain reaction (RT-PCR) was subsequently used for HCMV-late mRNA detection. Ganciclovir therapy was given to both positive group and negative group for comparison of therapeutic effectiveness.

RESULTSNineteen out of 46 CFU-MK culture cell specimens with positive HCMV-DNA by PCR or positive CMV-IgM by enzyme linked immunosorbent assay (ELISA) from serum of peripheral blood showed positive for HCMV-late mRNA. While, the remaining 27 were negative. Sixteen positive responders to ganciclovir therapy were observed amongst those with positive HCMV-DNA. Whereas, only 4 positive responders to ganciclovir therapy were noticed amongst those with negative HCMV-DNA. The curative effectiveness in positive group was significantly higher than that in negative group (P < 0.01).

CONCLUSIONHCMV can directly infect CFU-MK, which might be one of the mechanisms responsible for ITP. Ganciclovir is an effective therapy resulting in an increase in thrombocyte in ITP patients whose HCMV-late mRNA was positive in their CFU-MK.

Adolescent ; Antibodies, Viral ; immunology ; Antiviral Agents ; therapeutic use ; Blood Platelets ; drug effects ; immunology ; Cells, Cultured ; Child ; Child, Preschool ; Cytomegalovirus ; drug effects ; genetics ; pathogenicity ; Cytomegalovirus Infections ; drug therapy ; genetics ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Ganciclovir ; therapeutic use ; Humans ; Immunoglobulin M ; immunology ; Infant ; Male ; Megakaryocyte Progenitor Cells ; drug effects ; metabolism ; Purpura, Thrombocytopenic, Idiopathic ; complications ; drug therapy ; immunology ; RNA, Messenger ; RNA, Viral ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction