Robot versus video-assisted thoracoscopic thymectomy for large thymic epithelial tumors: a propensity-matched analysis.

BACKGROUND: Both video-assisted thoracoscopic surgery (VATS) thymectomy and robot-assisted thoracoscopic surgery (RATS) thymectomy have been suggested as technically sound approaches for early-stage thymic epithelial tumors. However, the choice of VATS or RATS thymectomy for large and advanced thymic epithelial tumors remains controversial. In this study, the perioperative outcomes of VATS and RATS thymectomy were compared in patients with large thymic epithelial tumors (size ≥5.0 cm). METHODS: A total of 113 patients with large thymic epithelial tumors who underwent minimally invasive surgery were included. Sixty-three patients underwent RATS, and 50 patients underwent VATS. Patient characteristics and perioperative variables were compared. RESULTS: Compared with the VATS group, the RATS group experienced a shorter operation time (median: 110 min vs.130 min; P < 0.001) and less blood loss (30.00 ml vs. 100.00 ml, P < 0.001). No patients in the RATS group needed conversion to open surgery, but in the VATS series, five patients required conversion to open procedures (0% vs. 14.29%, P = 0.054). The rate of concomitant resection in the RATS group was similar to that in the VATS group (11.43% vs. 5.71%; P = 0.673). There was no significant difference between the two groups in the duration of chest tube (P = 0.587), postoperative complications (P = 1.000), and the duration of postoperative hospital stay (P = 0.141). CONCLUSION: For large thymic epithelial tumors, RATS thymectomy can be performed safely and effectively in a radical fashion. Due to the advanced optics and precise instrument control, concomitant resections can be easily achieved in larger thymic epithelial tumors using the robotic approach.

Bioinspired PROTAC-induced macrophage fate determination alleviates atherosclerosis.

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.

Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9.

Lung adenocarcinoma (LUAD) characterized by high metastasis and mortality is the leading subtype of non-small cell lung cancer. Evidence shows that some microRNAs (miRNAs) may act as oncogenes or tumor suppressor genes, leading to malignant tumor occurrence and progression. To better understand the molecular mechanism associated with miRNA methylation in LUAD progression and clinical outcomes, we investigated the correlation between miR-148a-3p methylation and the clinical features of LUAD. In the LUAD cell lines and tumor tissues from patients, miR-148a-3p was found to be significantly downregulated, while the methylation of miR-148a-3p promoter was notably increased. Importantly, miR-148a-3p hypermethylation was closely associated with lymph node metastasis. We demonstrated that mitogen-activated protein (MAP) kinase kinase kinase 9 (MAP3K9) was the target of miR-148a-3p and that MAP3K9 levels were significantly increased in both LUAD cell lines and clinical tumor tissues. In A549 and NCI-H1299 cells, overexpression of miR-148a-3p or silencing MAP3K9 significantly inhibited cell growth, migration, invasion and cytoskeleton reorganization accompanied by suppressing the epithelial-mesenchymal transition. In a nude mouse xenograft assay we found that tumor growth was effectively inhibited by miR-148a-3p overexpression. Taken together, the promoter methylation-associated decrease in miR-148a-3p could lead to lung cancer metastasis by targeting MAP3K9. This study suggests that miR-148a-3p and MAP3K9 may act as novel therapeutic targets for the treatment of LUAD and have potential clinical applications.

Doxorubicin-loaded hydrogen peroxide self-providing copper nanodots for combination of chemotherapy and acid-induced chemodynamic therapy against breast cancer.

In recent years, chemodynamic therapy (CDT) has gained increasing interest in cancer treatment. In contrast to photodynamic therapy and sonodynamic therapy, extrinsic excitations such as laser or ultrasound are not required in CDT. As a result, the CDT performance is not limited by the penetration depth of the external irritation. However, CDT relies heavily on hydrogen peroxide (H2O2) in the tumour microenvironment (TME). Insufficient H2O2 in the TME limits the CDT performance, and the most reported methods to produce H2O2 in the TME are dependent on oxygen supply, which is restricted by the hypoxic TME. In this study, H2O2 self-providing copper nanodots were proposed, and the drug doxorubicin (DOX) was successfully loaded to construct DOX-nanodots. Our results showed that the nanodots produced H2O2 in the weakly acidic TME due to the peroxo group and further generated the most active hydroxyl radical (OH) through the Fenton-like reaction. This process was pH-dependent and did not occur in a neutral environment. In addition to OH, the nanodots also produced singlet oxygen (1O2) and superoxide anions (O2-) in the cancer cells. The copper nanodots performed promising CDT against breast cancer in vitro and in vivo, with enhanced cell apoptosis and decreased cell proliferation. The combination of chemotherapy and CDT using DOX-nanodots further improved the therapeutic effects. The treatments showed good biocompatibility with no obvious toxicity in major tissues, possibly due to the specific OH generation in the weakly acidic TME. In summary, the H2O2 self-providing copper nanodots in combination with DOX showed promising cancer-curing effects due to the oxygen-independent and tumour-specific production of reactive oxygen species and the cooperation of chemotherapy.

Preparation, characterization and in vitro-in vivo evaluation of bortezomib supermolecular aggregation nanovehicles.

BACKGROUNDS: Intolerable toxicity and unsatisfactory therapeutic effects are still big problems retarding the use of chemotherapy against cancer. Nano-drug delivery system promised a lot in increasing the patients' compliance and therapeutic efficacy. As a unique nano-carrier, supermolecular aggregation nanovehicle has attracted increasing interests due to the following advantages: announcing drug loading efficacy, pronouncing in vivo performance and simplified production process. METHODS: In this study, the supermolecular aggregation nanovehicle of bortezomib (BTZ) was prepared to treat breast cancer. RESULTS: Although many supermolecular nanovehicles are inclined to disintegrate due to the weak intermolecular interactions among the components, the BTZ supermolecules are satisfying stable. To shed light on the reasons behind this, the forces driving the formation of the nanovehicles were detailed investigated. In other words, the interactions among BTZ and other two components were studied to characterize the nanovehicles and ensure its stability. CONCLUSIONS: Due to the promising tumor targeting ability of the BTZ nanovehicles, the supermolecule displayed promising tumor curing effects and negligible systemic toxicity.

All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina.

The present study was designed to analyze the metabolites of all-trans-retinal (atRal) and compare the cytotoxicity of atRal versus its derivative all-trans-retinoic acid (atRA) in human retinal pigment epithelial (RPE) cells. We confirmed that atRA was produced in normal pig neural retina and RPE. The amount of all-trans-retinol (atROL) converted from atRal was about 2.7 times that of atRal-derived atRA after incubating RPE cells with 10 µmol/L atRal for 24 h, whereas atRA in medium supernatant is more plentiful (91 vs. 29 pmol/mL), suggesting that atRA conversion facilitates elimination of excess atRal in the retina. Moreover, we found that mRNA expression of retinoic acid-specific hydroxylase CYP26b1 was dose-dependently up-regulated by atRal exposure in RPE cells, indicating that atRA inactivation may be also initiated in atRal-accumulated RPE cells. Our data show that atRA-caused viability inhibition was evidently reduced compared with the equal concentration of its precursor atRal. Excess accumulation of atRal provoked intracellular reactive oxygen species (ROS) overproduction, heme oxygenase-1 (HO-1) expression, and increased cleaved poly(ADP-ribose) polymerase 1 (PARP1) expression in RPE cells. In contrast, comparable dosage of atRA-induced oxidative stress was much weaker, and it could not activate apoptosis in RPE cells. These results suggest that atRA generation is an antidotal metabolism pathway for atRal in the retina. Moreover, we found that in the eyes of ABCA4-/-RDH8-/- mice, a mouse model with atRal accumulation in the retina, the atRA content was almost the same as that in the wild type. It is possible that atRal accumulation simultaneously and equally promotes atRA synthesis and clearance in eyes of ABCA4-/-RDH8-/- mice, thus inhibiting the further increase of atRA in the retina. Our present study provides further insights into atRal clearance in the retina.

Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3ß signaling pathway.

OBJECTIVE: We investigated the protective effect of tetramethylpyrazine (TMP) on injury related to acute myocardial ischemia (AMI) induced by isoproterenol (ISO). MATERIALS AND METHODS: Rats were randomly assigned to five groups: control, ISO, ISO + propranolol (10 mg/kg), ISO + TMP (10 mg/kg) and ISO + TMP (20 mg/kg). The rats in the three ISO + groups were pretreated with propranolol or TMP, while the rats in the control and ISO groups were pretreated with an equal volume of saline. Afterwards, the rats in the four administration groups were subcutaneously injected with ISO for two consecutive days. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß in the serum were measured using ELISA. The expressions of B-cell lymphoma-associated X-2 (Bax-2), B-cell lymphoma-2 (Bcl-2), phosphoinositide-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3ß (GSK-3ß), MDA5 and SOD1 were determined using western blotting assay. The phosphorylation of PI3K, Akt and GSK-3ß were also determined using western blotting assay. The left ventricles of the rats were extracted and stained using hematoxylin and eosin (H&E). The ST segment was recorded using electrocardiograms (ECGs). RESULTS: Administration of TMP (10, 20 mg/kg) reduced the levels of MDA and CK and the activities of SOD and LDH in the serum. Pretreatment with TMP significantly reduced the levels of pro-inflammatory cytokines, including IL-1ß, IL-6 and TNF-α. Treatment with TMP also improved the histopathological alteration and decreased the ST elevation. Furthermore, TMP ameliorated the expressions of Cu, SOD1, MDA5, Bax-2, Bcl-2, p-PI3K, p-Akt and p-GSK-3ß in ISO-induced rats. CONCLUSIONS: Tetramethylpyrazine protected against injury due to AMI by regulating the PI3K/Akt /GSK-3ß signaling pathway.

Clinical significance of analysis of the level of blood fat, CRP and hemorheological indicators in the diagnosis of elder coronary heart disease.

OBJECTIVE: To investigate the levels of blood fat, C-reactive protein (CRP) and hemorheological indicators in the elder patients with coronary heart disease (CHD), so as to provide evidence for prospective study and treatment of elder CHD. METHODS: We collected the clinical data of 127 elder CHD patients who admitted to this hospital between July 2016 and December 2017 to detect the levels of blood fat, CRP and hemorheological indicators. RESULTS: In elder CHD patients, levels of the total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-C) were significantly higher than the normal reference, and comparison with the control group also showed significant increases (p < 0.01); average levels of the high-density lipoprotein cholesterin (HDL-C), phospholipid (PL), lipoprotein a [LP (a)] and free fatty acid were in the range of normal reference. Abnormal levels of TC, TG, LDL-C and HDL-C were identified in 59.06%, 58.27%, 51.18% and 18.11% of the elder CHD patients, most of which were concomitant with obesity or hypertension, and levels of these indicators were significantly higher than those in the control group with statistically significant differences (p < 0.01). Comparisons of the age, gender distribution, hypotension, exercise and sleep showed that differences had no statistical significance (p > 0.05). In comparison with the control group, the levels of CRP, the whole blood viscosities at high and low shears, plasma viscosity, hematocrit value, aggregation index and rigidity index of red blood cells (RBC) were all higher than those in the control group, and the differences had statistical significance (p < 0.01). However, the erythrocyte sedimentation rate (ESR), deformity index of RBC, blood flow rates in the bilateral middle cerebral arteries (MCA), anterior cerebral arteries (ACA), terminal internal carotid artery (TICA), posterior cerebral arteries (PCA), vertebral arteries (VA) and basilar artery (BA) were significantly lower than those in the control group, and the differences had statistical significance (p < 0.05 or 0.01). CONCLUSION: In elder CHD patients, anomaly is mainly seen in levels of TC, TG and LDL-C with concentrated, adhesive and aggregating blood.

[Application of machine learning in the CRISPR/Cas9 system].

The third generation of the CRISPR/Cas9-mediated genome fixed-point editing technology has been widely used in the field of gene editing and gene expression regulation. How to improve the on-target efficiency and specificity of this system, as well as reduce its off-target effects are always the bottleneck in its development. Machine learning provides novel methods to the problems of the CRISPR/Cas9 system, and CRISPR/Cas9-based machine learning has recently become a very hot research topic. In this review, we firstly outline the mechanism of the CRISPR/Cas9 system. Subsequently, we elaborate the current issues of CRISPR/Cas9, including low efficiency and potential off-target effects, and sequence-recognizing limitation from protospacer adjacent motif (PAM). Finally, we summarize the applications of methods within the machine learning framework for optimizing the CRISPR/Cas9 system, such as optimized single-guide RNA (sgRNA) design, CRISPR/Cas9 cleavage efficiency prediction, off-target effects evaluation, gene knock-out as well as high-throughput functional genetic screening and prospects for development.

CuS Nanodot-Loaded Thermosensitive Hydrogel for Anticancer Photothermal Therapy.

The purpose of this research is to establish an injectable hydrogel encapsulating copper sulfide (CuS) nanodots for photothermal therapy against cancer. The CuS nanodots were prepared by one-pot synthesis, and the thermosensitive Pluronic F127 was used as the hydrogel matrix. The CuS nanodots and the hydrogel were characterized by morphous, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation, and rheology features. The effects of the CuS nanodots and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects, and systemic toxicity of the hydrogel were assessed in tumor bearing mouse model. The CuS nanodots with a diameter of about 8 nm exhibited satisfying serum stability, photoheat conversion ability, and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanodot-loaded hydrogel shows a phase transition at body temperature and, as a result, a long retention in vivo. The photothermal-agent-embedded hydrogel played a promising photothermal therapeutic effect in the tumor bearing mouse model with low systemic toxicity after peritumoral administration.

[Effect of low dose propofol on biological behavior of esophageal squamous cell carcinoma cell line Eca109].

AIM: To detect the effect of low dose propofol on the proliferation, apoptosis, migration, and invasion of esophageal squamous cell carcinoma cell line Eca109. METHODS: The proliferation, apoptosis, migration, and invasion of esophageal squamous cell carcinoma cell line Eca109 were detected by MTT assay, flow cytometry, transwell assay respectively. The effect of low dose propofol on expression of heme oxygenase-1 (HO-1) was confirmed by Real-time quantitative PCR. RESULTS: Low dose propofol could inhibit the proliferation, migration, invasion and promate the apoptosis of esophageal squamous cell carcinoma cell line Eca109. And low dose propofol increased the expression of HO-1 mRNA in a dose-dependment manner. CONCLUSION: Low dose propofol affects the biological behavior of esophageal squamous cell carcinoma cell line Eca109, which has a relationship with increasing the expression of HO-1.

[Effect of N-acetylcysteine on malondialdehyde and superoxide dismutase in hepatic tissue of mice with Schistosomiasis japonica].

90 mice were randomly divided into six groups: normal control, infected control, long-term drug use group 1 (L1), long-term drug use group 2 (L2), short-term drug use group 1 (S1) and short-term drug use group 2 (S2). Mice in all groups except those in the normal control group were infected with 30 cercariae of Schistosoma japonicum through abdominal skin. N-acetylcysteine (NAC) solution was orally given to mice in L1 and L2 groups, 200 mg/kg and 400 mg/kg, respectively, 2 times/d from the day of infection, while for S1 and S2 groups, 200 mg/kg and 400 mg/kg, respectively, 2 times/d from the 42th day after L2 infection. Mice in the groups of normal control, infected control, L1 and L2 were sacrificed either on day 42 or day 56 after infection, while those in S1 and S2 were sacrificed on day 56 after infection. Number and area of the single egg granuloma were measured with computer image analysis software. The concentration of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in serum and hepatic tissue were detected. The number of "+" single egg granulomas in the liver of mice in L1 was the fewest by 3.04, followed by those in S1, by 4.87. The results indicated that the level of MAD in hepatic tissue of L2 (9.2-9.3 nmol/mg)was markedly lower than that of L1 (P < 0.05), and the level of SOD in hepatic tissue of L1 was 170.00-190.00 U/(g x pro), similar to those of S1 and L2 at the 42th day (P > 0.05), but the level in L2 at the 56th day was close to that of S2 (P > 0.05). Hence, NAC may retard the formation of single egg granulomas in the liver of infected mice, and may regulate the concentration of MDA and the activity of SOD in the liver.

Characterization of the aminated agarose nanoparticles labeled with fluorescein isothiocyanate.

Incorporating an organic fluorescence agent into nanoparticles can significantly promote its fluorescent efficiency. In this article, a novel fluorescein isothiocyanate labeling aminated agarose (FITC-AA) was synthesized and tested as an effective fluorescent labeling agent. FITC-AA could spontaneously form nanoparticles with a diameter less than 200 nm below 37°C due to gelling effect of the agarose. Cell culture experiments confirmed that 3T3 fibroblast cells could be marked by fluorescent FITC-AA nanoparticles and the labeling time sustained longer than by FITC alone. This finding demonstrates that the fluorescent labeling of cells can be enhanced when fluorescent nanoparticles are used as markers.

[Effect of alpha-terthienyl on protein, esterase and lipid peroxidation of Aedes albopictus larvae].

OBJECTIVE: To study the effect of alpha-terthienyl (alpha-T) on protein, esterase and lipid peroxidation of Aedes albopictus larvae. METHODS: Sensitive and resistant strains of Aedes albopictus stage IV larvae were used. Bradford method was used to detect protein content. The breeding fluid of experiment group contained alpha-T (5.34 microg/L), and control group contained only acetone (3.95 microg/L). Histochemistry method was used to detect esterase activity. Larvae in the experiment group were cultured in fluid containing alpha-T (6.24 microg/L) but no alpha-T in the control group. TBA method was used to detect malondialdehyde (MDA). Larvae of the sensitive strain were divided into 5 sub-groups: A - acetone control (containing acetone 3.95 microg/L), B - ultra-violet irradiation (UV) control (same with A but treated by UV), C, D, E - experiment groups with alpha-T (4.58, 5.34 and 6.24 microg/L respectively). All groups were kept in dark condition for 1 hour, followed by UV for 1 hour (except group A), then fed under normal condition. RESULTS: With UV and alpha-T, the protein content of experiment group (1.225 mg/ml) was higher than that of control (1.120 mg/ml) (P<0.05) in sensitive strain; that of experiment group (1.199 mg/ml) was higher than that of control (1.114 mg/ml) (P<0.05) in the resistant strain. After 2, 4, 6, and 8 hour treated by both alpha-T and UV, the esterase activity all decreased in experiment group, and reached to the lowest 8 hours later (P<0.05). MDA contents was 2.286 nmol/mg protein in acetone control group and 2.322 nmol/mg protein in UV control, but 3.156, 4.188 and 4.684 nmol/mg protein respectively in the 3 experiment groups after treated by alpha-T and UV. The higher dose of alpha-T, the higher content of MDA (P<0.05). CONCLUSION: Under UV, alpha-T can increase the protein and MDA content of the larvae of Ae. albopictus but decrease the esterase activity.

[Effect of N-acetylcysteine on the egg granuloma in hepatic tissue of mice with Schistosomosis japonica].

OBJECTIVE: To study the effect of N-acetylcysteine (NAC) on the egg granuloma in hepatic tissue of mice infected with Schistosoma japonicum. METHODS: 36 mice were randomly divided into normal group, infected group and NAC group, each with 12 mice. The mice in the latter two groups were each infected with 25+/-2 cercariae of S. japonicum through the skin of abdomen. NAC solution was orally given to the mice of NAC group, 200 mg/kg, 2 times/d from the day of infection through to the 42nd day. Mice in the other 2 groups were given 2 ml normal saline daily. The mice were all sacrificed at the end of the 42nd day and their livers were collected for pathologic observation. Area of the egg granuloma was measured with computer image analysis software. Concentration of nitric oxide (NO) and reduced glutathione hormone (GSH), and the activity of glutathione peroxidase (GSH-PX) in serum and hepatic tissue, and the activity of inducible nitric oxide synthase (iNOS) in the hepatic tissue were all detected. RESULTS: Number of the single egg granuloma of "+,++,+++" grade were 1.80+/-0.25, 1.37+/-0.23 and 0.53+/-0.15 respectively in NAC treated group, which were less than those of infected group (3.70+/-0.28, 2.77+/-0.25 and 2.00+/-0.14 respectively) (P<0.05). The serum NO and GSH concentration was 0.53+/-0.17 and 229.66+/-9.47 respectively in NAC group, lower than those of infected group (2.64+/-0.31 and 312.47+/-18.55 respectively) (P<0.05), but its GSH-PX activity was 1101.99+/-140.81, higher than that of infected group (663.66+/-25.59) (P<0.05). The concentration of NO and GSH, and the activity of iNOS and GSH-PX in hepatic tissue of NAC group were 6.85+/-0.30, 13.44+/-0.40, 358.40+/-19.15 and 110.84+/-10.93 respectively, lower than those in infected group (8.26+/-1.69, 28.40+/-0.56, 1132.44+/-52.82 and 226.26+/-16.25 respectively) (P<0.05). CONCLUSION: NAC may have the effect of retarding pathological change of the liver, which may associate with the decrease of NO and GSH in serum and hepatic tissue and iNOS activity in the tissue.

[Toxicity of alpha-terthienyl to the larvae of Aedes albopictus].

OBJECTIVE: To investigate the toxicity of alpha-terthienyl to the larvae of Aedes albopictus, its influencing factors and effect on the larva development. METHODS: Under experimental ultraviolet-A (UVA), the number of dead,pupal or eclosive mosquito larvae was determined on the condition of different doses of alpha-terthienyl and different disposal time in the dark; the number of dead larvae was also determined under sunlight on the condition of different doses of alpha-terthienyl and different disposal time to water. RESULTS: The LC50 of alpha-terthienyl to Aedes albopictus larvae was 2.37 microg/L under UVA. The best effect was shown when the larvae were incubated with alpha-terthienyl 3 h in dark. Alpha-terthienyl could significantly inhibit the larva development and the emergence of the pupae. Under strong sunlight, the larvae were quickly killed by high concentration alpha-terthienyl. The 24 hours effect of alpha-terthienyl was better when it was applied at 5 AM than that of at 10 AM and 1 PM. CONCLUSION: Alpha-terthienyl is an effective, practicable larvicide which prohibits the growth and development of the larvae of Aedes albopictus.

[Ultrastructural dynamic observation on murine schistosomal hepatic fibrosis].

OBJECTIVE: To explore possible mechanisms of hepatic fibrosis by investigating the ultrastructural dynamic changes of liver tissue, especially several kinds of cells related to hepatic fibrosis. METHODS: Murine schistosomal hepatic fibrosis model was established by infecting mice with Schistosoma japonicum cercariae. Routine transmission electron microscopy was used to observe the liver tissue. H.E. staining was used for examining the pathological changes. RESULTS: H.E. staining showed that the model was established successfully. Ultrastructural observation showed that at the 6th week after infection, the necrosis of hepatocytes around the acute granulomas occurred; the number of sinusoidal endothelial fenestrae and vitamin A droplets in fat-storing cells decreased; large phagosomes and rough endoplasmic reticulum could be seen in the cytoplasm of Kupffer's cells. At the 8th week, steatosis was found in some hepatocytes, some microvilli emerged on a few inter-hepatocytic surfaces and the inter-hepatocytic spaces were enlarged. Large collagen fibrillar bundles filled in the perisinusoidal spaces, and capillarization of hepatic sinusoids was observed. Secretory vesicles filled with collagen fibrils appeared in the cytoplasm of fat-storing cells with large amount of collagenous fiber bundles surround the cells. Rough endoplasmic reticulum increased in Kupffer's cells. At the 10th week, fat-storing cells were activated and transformed into myofibroblasts. At the 12th week, the number of myofibroblasts decreased but that of fibroblasts and fiber cells increased. CONCLUSION: Activation of fat-storing cells and transformation from fat-storing cells into myofibroblasts are the critical link in the development of hepatic fibrogenesis following schistosome infection. Kupffer's cells, necrotic hepatocytes and sinusoidal endothelial cells may relate to the activation of fat-storing cells. Capillarization of hepatic sinusoids possibly accelerates the development of hepatic fibrosis.

Chinese phlebotomine sandflies of the subgenus Adlerius Nitzulescu, 1931 (Diptera: Psychodidae) and the identity of P. sichuanensis Leng & Yin, 1983. II--genotyping and numerical analysis.

The authors carried out isoenzyme characterization and genotype comparison studies for Phlebotomus chinensis and Phlebotomus sichuanensis images collected from their holotype/paratype original localities: West Mountain, West Suburb, Beijing and Lixian County, Sichuan Province. Numerical analysis was carried out and the dendrogram of four species of Adlerius was drawn up according to morphological characteristics of these four species. The results showed that P. chinensis and P. sichuanensis can be identified enzymatically in PGM and the MDH-2 allele also differs in P. chinensis from Beijing and. P. sichuanensis. The dendrogram of four Adlerius species showed that P. fengi and P. longiductus are very similar and they clustered first, then P. sichuanensis combine with them to form a combined group. P. chinensis is a separate group from other three. These two groups come to combine at last. Above results have proved that P. sichuanensis is an isolate species instead of a so-called large type P. chinensis.