Nuclear KRT19 is a transcriptional corepressor promoting histone deacetylation and liver tumorigenesis.

BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 and REST corepressor 1, components of the corepressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing histone deacetylase 1 and REST corepressor 1 interaction, thus increasing the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha ( HNF4A ), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to histone deacetylase 1 inhibitors especially in combination with lenvatinib. CONCLUSIONS: Our data show that nuclear KRT19 acts as a transcriptional corepressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.

Modelling and Mitigating Secondary Crash Risk for Serial Tunnels on Freeway via Lighting-Related Microscopic Traffic Model with Inter-Lane Dependency.

This paper models and mitigates the secondary crash (SC) risk for serial tunnels on the freeway which is incurred by traffic turbulence after primary crash (PC) occurrence and location-heterogeneous lighting conditions along serial tunnels. A traffic conflict approach is developed where SC risk is quantified using a surrogate safety measure based on the simulated vehicle trajectories after PC occurs from a lighting-related microscopic traffic model with inter-lane dependency. Numerical examples are presented to validate the model, illustrate SC risk pattern over time, and evaluate the countermeasures for SC, including adaptive tunnel lighting control (ATLC) and advanced speed and lane-changing guidance (ASLG) for connected vehicles (CVs). The results demonstrate that the tail of the stretching queue on the PC occurrence lane, the adjacent lane of the PC-incurred queue, and areas near tunnel portals are high-risk locations. In serial tunnels, creating a good lighting condition for drivers is more effective than advanced warnings in CVs to mitigate SC risk. Combined ATLC and ASLG is promising since ASLG informs CVs of an immediate response to traffic turbulence on the lane where PC occurs and ATLC alleviates SC risks on adjacent lanes via smoothing the lighting condition variations and reducing inter-lane dependency.

Characteristics of boundary layer ozone and its effect on surface ozone concentration in Shenzhen, China: A case study.

In late September 2019, the longest and most extensive ozone (O3) pollution process occurred at Pearl River Delta. Base on the observational data, surface-level O3, vertical distribution characteristics boundary layer O3 as well as its effect on surface-level O3 are thoroughly analyzed. The O3 lidar results showed similar vertical O3 profiles both in pollution episodes and clean periods, from which a high O3 concentration layer between 300 and 500 m and a sub-high O3 concentration layer between 1300 and 1700 m (near the top of the mixing layer) can be found. Besides, the downward O3 transport paths from the high/sub-high O3 concentration layers could be observed along with the boundary layer evolution: At nighttime, large amounts of O3 were effectively stored into the residual layer (RL). Due to the upward development of Mixing layer (ML) in early morning, atmospheric vertical mixing carried the O3 inside the RL down to the surface, which led to a rapid increase in the surface-level O3. The sub-high O3 layer began the downward mixing at noon, and became well-mixed after the boundary layer was fully developed in the afternoon, by which the near surface O3 pollution deteriorated again. Further analysis of the heavy O3 pollution episodes show that, the high O3 concentration inside the RL contributed 54% ± 6% of the surface-level O3 at 9:00 LT and the average contribution of O3 in the sub-high concentration layer to the surface-level O3 at 14:00 LT was 26% ± 9%. Based on the quantitative analysis of the observational data, this paper focus to reveal the importance of the contribution of O3 inside the RL and near the top of the ML to the surface O3.

[Effect of indwelling drainage tube and extubation time on recessive hemorrhage and functional recovery after total hip arthroplasty].

OBJECTIVE: To study and compare the effect of indwelling drainage tube and extubation time on occult hemorrhage and functional recovery after total hip arthroplasty(THA). METHODS: From July 2017 to June 2018, 123 patients who underwent THA in our hospital for the first time were selected as the subjects of study. According to whether the drainage tube was retained or not and the time of extubation, they were divided into three groups:in group A, 41 patients (24 males, 17 females, age 53 to 77 years) did not put drainage tube after THA;in group B, 41 patients were removed 24 hours after THA, 26 males and 15 females, aged 55 to 74 years;in group C, 41 patients were removed 48 hours after THA, 25 males and 16 females, aged 52 to 75 years. The VAS score of pain 72 hours after THA, the total and recessive blood loss, the time of starting functional exercise, and the incidence of postoperative limb swelling were recorded. All the patients were followed up for one year after discharge. Harris hip score was used to evaluate the degree of hip function recovery one year after operation. RESULTS: The occult blood loss of group A, B and C were(513.6±25.3), (521.7±33.4), (519.3±29.8) ml, respectively, with no significant difference(P>0.05). There was no significant difference in blood loss in operation among the three groups(P>0.05). In group B and C, the postoperative apparent blood loss was more than that in group A (P<0.05). There was no significant difference in VAS scores of the three groups before and 72 hours after operation (P>0.05). The time of getting out of bed in group A was shorter than that in group B and C (P<0.05), and that in group B was shorter than that in group C(P<0.05). The Harris hip score at 1 year after operationof the three groups was significantly higher than that of before operation (P<0.05). There was no significant difference in Harris hip score before and after operation among three groups (P>0.05). There was no significant difference in the incidence of complications among three groups (P>0.05). CONCLUSION: Whether the drainage tube is left or not and the time of extubation have no significant effect on the latent blood loss and functional recovery after THA, but without drainage tube after THA can reduce the apparent blood loss, patients can get out of bed at 6 hours after THA, which is more conducive to the recovery and nursing of patients.

PCR Detection and Phylogenetic Analysis of Megalocytivirus Isolates in Farmed Giant Sea Perch Lates calcarifer in Southern Taiwan.

The Megalocytivirus genus includes three genotypes, red sea bream iridovirus (RSIV), infectious spleen and kidney necrosis virus (ISKNV), and turbot reddish body iridovirus (TRBIV), and has caused mass mortalities in various marine and freshwater fish species in East and Southeast Asia. Of the three genotypes, TRBIV-like megalocytivirus is not included in the World Organization for Animal Health (OIE)-reportable virus list because of its geographic restriction and narrow host range. In 2017, 39 cases of suspected iridovirus infection were isolated from fingerlings of giant sea perch (Lates calcarifer) cultured in southern Taiwan during megalocytivirus epizootics. Polymerase chain reaction (PCR) with different specific primer sets was undertaken to identify the causative agent. Our results revealed that 35 out of the 39 giant sea perch iridovirus (GSPIV) isolates were TRBIV-like megalocytiviruses. To further evaluate the genetic variation, the nucleotide sequences of major capsid protein (MCP) gene (1348 bp) from 12 of the 35 TRBIV-like megalocytivirus isolates were compared to those of other known. High nucleotide sequence identity showed that these 12 TRBIV-like GSPIV isolates are the same species. Phylogenetic analysis based on the MCP gene demonstrated that these 12 isolates belong to the clade II of TRBIV megalocytiviruses, and are distinct from RSIV and ISKNV. In conclusion, the GSPIV isolates belonging to TRBIV clade II megalocytiviruses have been introduced into Taiwan and caused a severe impact on the giant sea perch aquaculture industry.

Effect of indwelling drainage tube and extubation time on recessive hemorrhage and functional recovery after total hip arthroplasty / 中国骨伤

OBJECTIVE@#To study and compare the effect of indwelling drainage tube and extubation time on occult hemorrhage and functional recovery after total hip arthroplasty(THA).@*METHODS@#From July 2017 to June 2018, 123 patients who underwent THA in our hospital for the first time were selected as the subjects of study. According to whether the drainage tube was retained or not and the time of extubation, they were divided into three groups:in group A, 41 patients (24 males, 17 females, age 53 to 77 years) did not put drainage tube after THA;in group B, 41 patients were removed 24 hours after THA, 26 males and 15 females, aged 55 to 74 years;in group C, 41 patients were removed 48 hours after THA, 25 males and 16 females, aged 52 to 75 years. The VAS score of pain 72 hours after THA, the total and recessive blood loss, the time of starting functional exercise, and the incidence of postoperative limb swelling were recorded. All the patients were followed up for one year after discharge. Harris hip score was used to evaluate the degree of hip function recovery one year after operation.@*RESULTS@#The occult blood loss of group A, B and C were(513.6±25.3), (521.7±33.4), (519.3±29.8) ml, respectively, with no significant difference(>0.05). There was no significant difference in blood loss in operation among the three groups(>0.05). In group B and C, the postoperative apparent blood loss was more than that in group A (0.05). The time of getting out of bed in group A was shorter than that in group B and C (0.05). There was no significant difference in the incidence of complications among three groups (>0.05).@*CONCLUSION@#Whether the drainage tube is left or not and the time of extubation have no significant effect on the latent blood loss and functional recovery after THA, but without drainage tube after THA can reduce the apparent blood loss, patients can get out of bed at 6 hours after THA, which is more conducive to the recovery and nursing of patients.

Impact of typhoon periphery on high ozone and high aerosol pollution in the Pearl River Delta region.

This paper analyzes observation data in the Pearl River Delta (PRD) region from 2012 to 2013, and explores the impact of typhoon periphery on high ozone and high aerosol pollution episodes (double high episodes). Observation analysis show that severe tropical storms to severe typhoons are mainly located in the range of 10°N-30°N, 116°E-135°E when double high episodes occur. Meanwhile, obvious high temperature, low humidity, low wind speed, high actinic flux, high aerosol optical depth (AOD), and high single scattering albedo (SSA) can be observed in double high episodes. The diurnal cycle of the PM2.5 is significant in double high episodes, and the average peak concentration in the afternoon can exceed 90 µg/m3. The diurnal cycle of PM2.5 in non-double high episodes is not significant, and the average value is about 34-39 µg/m3. The ozone peak concentration in double high episodes is 81-103 ppbv, which is about 27-40 ppbv higher than that of non-double high episodes. High correlation can be found between the aerosol and ozone diurnal cycles in double high episodes, and r2 reaches 0.76. In double high episodes, black carbon, nitrate, and sea salt decrease while sulfate, ammonium, secondary organic carbon, and total PM2.5 significantly increase in the afternoon. The growth of PM2.5 in double high episodes is mainly contributed by scattered fine particles from photochemical processes and transmission. The mechanisms that control the double high episodes in the PRD are described below. Ozone and aerosol begin to accumulate under unfavorable meteorological conditions. Via local photochemical processes and external transport, the scattered aerosol increases and leads to an increase in multiple scattering and actinic radiation, which is in turn more favorable for photochemical reaction and further increases the ozone concentration. Meanwhile, high oxidizability promotes the formation of scattered aerosol, creating positive feedback. In addition, the scattered aerosol increases backscattering, which increases the photolysis rate and ozone concentration in the middle and upper boundary layer. Meanwhile, downdraft and turbulence transports high-concentration ozone to the ground.

[Treatment of Pipkin type I and II femoral head fractures through modified Smith-Peterson approach and modified Hardinge approach-a case-control studies].

OBJECTIVE: To compare clinical results of treatment of Pipkin type I and II femoral head fractures through modified Smith-Peterson(S-P) approach and modified Hardinge approach. METHODS: From July 2005 to July 2014, 42 patients with Pipkin type I and II femoral head fractures were treated with operation. A total of 23 patients in anterior group was treated with modified S-P approach including 17 males and 6 females with an average age of (29.3±9.4) years old, 5 cases of type I by excision of the fragement, 3 cases of type I and 15 cases of type II cases by fixation of the fragement. While a total of 19 patients in the lateral group was treated with modified Hardinge approach including 15 males and 4 females with an average age of (31.4±10.0) years old, 3 cases of type I by excision of the fragement, 4 cases of type I and 12 cases of type II by fixation of the fragement. Operative time, blood loss during operation and fracture healing time were observed and compared. The clinical and radiographic outcomes of the patients were measured using Thompson-Epstein scoring scale. The effect of hip reduction time of less than 6 h, 6 to12 h, and more than 12 h, the effect of surgery time within 24 h and more than 24 h after injury were compared. RESULTS: All patients were followed up from 24 to 60 months with an average of(30.29±6.95) months. The operation time (61.96±12.22) min, blood loss (46.09±18.03) ml, and (74.74±10.06) min, blood loss (72.11±19.88) ml in lateral group in the anterior group were better than those of lateral group(P<0.05). In anterior group, fracture healing time was(12.22±1.70) weeks, the results were excellent in 8 cases, good in 10 cases, fair in 4 cases and poor in 1 case, the excellent and good rate was 78.3%, the incidence of avascular necrosis of femoral head was 8.69%(2/23), and the incidence of heterotopic ossification was 13.04%(3/23). While in lateral group, the fracture healing time was(12.42±1.95) weeks, the results were excellent in 6 cases, good in 7 cases, fair in 3 cases and poor in 3 cases, the excellent and good rate was 68.4%, the incidence of avascular necrosis of femoral head was 10.53%(2/19), and the incidence of heterotopic ossification was 5.26%(1/19). There was no significant difference in fracture healing time, postoperative effect and postoperative complications between the anterior group and lateral group(P<0.05). The effect of patients with reduction time of hip dislocation less than 12 h was significantly better than that of more than 12 h, there was no significant difference in the effect between reduction time within 6 h and 6 to 12 h. There was no significant difference in the outcome between surgical patients within 24 h and more than 24 h after injury. CONCLUSIONS: Dislocated hip of Pipkin type I and II femoral head fractures should be closed reduction within 6 h. If conditions are limited, the reduction time can be accepted within 12 h. Both of modified S-P approach and modified Hardinge approach are effective in treating Pipkin type I and II femoral head fractures, and can obtain excellent outcomes. Moreover, modified S-P approach has advantage of less trauma, less blood loss, shorter operative time.

Treatment of Pipkin type I and II femoral head fractures through modified Smith-Peterson approach and modified Hardinge approach-a case-control studies / 中国骨伤

<p><b>OBJECTIVE</b>To compare clinical results of treatment of Pipkin type I and II femoral head fractures through modified Smith-Peterson(S-P) approach and modified Hardinge approach.</p><p><b>METHODS</b>From July 2005 to July 2014, 42 patients with Pipkin type I and II femoral head fractures were treated with operation. A total of 23 patients in anterior group was treated with modified S-P approach including 17 males and 6 females with an average age of (29.3±9.4) years old, 5 cases of type I by excision of the fragement, 3 cases of type I and 15 cases of type II cases by fixation of the fragement. While a total of 19 patients in the lateral group was treated with modified Hardinge approach including 15 males and 4 females with an average age of (31.4±10.0) years old, 3 cases of type I by excision of the fragement, 4 cases of type I and 12 cases of type II by fixation of the fragement. Operative time, blood loss during operation and fracture healing time were observed and compared. The clinical and radiographic outcomes of the patients were measured using Thompson-Epstein scoring scale. The effect of hip reduction time of less than 6 h, 6 to12 h, and more than 12 h, the effect of surgery time within 24 h and more than 24 h after injury were compared.</p><p><b>RESULTS</b>All patients were followed up from 24 to 60 months with an average of(30.29±6.95) months. The operation time (61.96±12.22) min, blood loss (46.09±18.03) ml, and (74.74±10.06) min, blood loss (72.11±19.88) ml in lateral group in the anterior group were better than those of lateral group(<0.05). In anterior group, fracture healing time was(12.22±1.70) weeks, the results were excellent in 8 cases, good in 10 cases, fair in 4 cases and poor in 1 case, the excellent and good rate was 78.3%, the incidence of avascular necrosis of femoral head was 8.69%(2/23), and the incidence of heterotopic ossification was 13.04%(3/23). While in lateral group, the fracture healing time was(12.42±1.95) weeks, the results were excellent in 6 cases, good in 7 cases, fair in 3 cases and poor in 3 cases, the excellent and good rate was 68.4%, the incidence of avascular necrosis of femoral head was 10.53%(2/19), and the incidence of heterotopic ossification was 5.26%(1/19). There was no significant difference in fracture healing time, postoperative effect and postoperative complications between the anterior group and lateral group(<0.05). The effect of patients with reduction time of hip dislocation less than 12 h was significantly better than that of more than 12 h, there was no significant difference in the effect between reduction time within 6 h and 6 to 12 h. There was no significant difference in the outcome between surgical patients within 24 h and more than 24 h after injury.</p><p><b>CONCLUSIONS</b>Dislocated hip of Pipkin type I and II femoral head fractures should be closed reduction within 6 h. If conditions are limited, the reduction time can be accepted within 12 h. Both of modified S-P approach and modified Hardinge approach are effective in treating Pipkin type I and II femoral head fractures, and can obtain excellent outcomes. Moreover, modified S-P approach has advantage of less trauma, less blood loss, shorter operative time.</p>

Sequestration of RNA by grass carp Ctenopharyngodon idella TIA1 is associated with its positive role in facilitating grass carp reovirus infection.

Previous report demonstrated that grass carp reovirus (GCRV) infection resulted in unlinking cellular stress granule formation from aggregation of grass carp Ctenopharyngodon idella TIA1 (CiTIA1). Here, we provided evidence to show that CiTIA1 bound to synthesized ssRNA and dsRNA in vitro. Both GST-pull down assay and RNA immunoprecipitation analysis confirmed the association between GCRV-specific RNA and GST-tagged CiTIA1 in C. idella kidney (CIK) cells. Furthermore, CiTIA1 was shown to protect dsRNA of virus-origin from degradation in CIK cells through Northern blot analysis. Finally, transient overexpression of CiTIA1 enhanced the replication efficiency of GCRV in CIK cells. Taken together, our results suggested that cellular CiTIA1 might facilitate GCRV replication through sequestrating and protecting viral RNA from degradation.

Proteomic analysis of cellular protein expression profiles in response to grass carp reovirus infection.

Grass carp (Ctenopharyngodon idella) hemorrhagic disease, caused by grass carp reovirus (GCRV), is emerging as a serious problem in grass carp aquaculture. To better understand the molecular responses to GCRV infection, two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization tandem mass spectroscopy were performed to investigate altered proteins in C. idella kidney (CIK) cells. Differentially expressed proteins in mock infected CIK cells and GCRV-infected CIK cells were compared. Twenty-three differentially expressed spots were identified (22 upregulated spots and 1 downregulated spot), which included cytoskeleton proteins, macromolecular biosynthesis-associated proteins, stress response proteins, signal transduction proteins, energy metabolism-associated proteins and ubiquitin proteasome pathway-associated proteins. Moreover, 10 of the corresponding genes of the differentially expressed proteins were quantified by real-time reverse transcription polymerase chain reaction to examine their transcriptional profiles. The T cell internal antigen 1 (TIA1) and Ras-GTPase-activating SH3-domain-binding protein1 (G3BP1) of the cellular stress granule pathway from grass carp C. idella (designated as CiTIA1 and CiG3BP1) were upregulated and downregulated during GCRV infection, respectively. The full-length cDNA of CiTIA1 was 2753 bp, with an open reading frame (ORF) of 1155bp, which encodes a putative 385-amino acid protein. The 2271 bp full-length cDNA of CiG3BP1 comprised an ORF of 1455 bp that encodes a putative 485-amino acid protein. Phylogenetic analysis revealed that the complete ORFs of CiTIA1 and CiG3BP1 were very similar to zebrafish and well-characterized mammalian homologs. The expressions of the cellular proteins CiTIA1 and CiG3BP1 in response to GCRV were validated by western blotting, which indicated that the GCRV should unlink TIA1 aggregation and stress granule formation. This study provides useful information on the proteomic and cellular stress granule pathway's responses to GCRV infection, which adds to our understanding of viral pathogenesis.

Study about Traditional Chinese Medicine syndrome of adolescent neck pain / 中国骨伤

<p><b>OBJECTIVE</b>To preliminarily research the formular about the Traditional Chinese Medicine (TCM) syndrome of adolescent neck pain.</p><p><b>METHODS</b>An observation table of adolescent neck pain syndromes was formulated,and 1 397 patients with adolescent neck pain were investigated to establish a database of adolescent neck pain. The Descriptive Statistical Analysis and Hierarchical Cluster Analysis were performed by statistical software.</p><p><b>RESULTS</b>Totally 60 TCM symptoms was clustered into 4 TCM syndromes by Hierarchical Cluster Analysis. The expert panel of TCM syndromes preliminarily formulate 4 TCM syndromes of adolescent neck pain by analyzing the result of Cluster Analysis and discussing their clinical experience.</p><p><b>CONCLUSION</b>Adolescent neck pain is a category of Tendon Trauma's Bi-syndrome of TCM. Ying, Wei, Qi and blood block caused by exopathy, strains, and internal injury is considered as the main pathogenesis of adolescent neck pain. Base on statistical result and expert's opinions, 4 TCM syndromes about adolescent neck pain were formulated: cold-dampness syndrome, dampness-heat blockage syndrome, liver-stagnation and spleen-deficiency syndrome, Qi and Yin deficiency of both heart and kidney syndrome.</p>

Soft tissue changes observed through musculoskeletal ultrasound in the treatment of knee osteoarthritis with needle-knife / 中国骨伤

<p><b>OBJECTIVE</b>To study soft tissue changes observed through musculoskeletal ultrasound (MSUS) in the treatment of knee osteoarthritis with needle-knife, so as to provide MSUS basis for needle-knife in the treatment of knee osteoarthritis.</p><p><b>METHODS</b>Forty patients with knee osteoarthritis treated in the Third Affiliated Hospital of Beijing University of Chinese Medicine from December 2011 to December 2012 were selected according to inclusion and exclusion criteria. All the patients were treated with needle-knife release method. The VAS scores and knee joint circumference were recorded before treatment and 2 weeks after treatment. The changes of knee joint hydrops articuli and joint synovial thickness were measured through MSUS.</p><p><b>RESULTS</b>The knee pain index was 6.850 +/- 1.417 before treatment and 2.790 +/- 1.299 after treatment;the index after treatment was lower than that of before treatment. The knee joint circumference was 407.320 +/- 45.151 mm before treatment and 391.240 +/- 41.129 mm after treatment; the knee joint circumference decreased after treatment. The amount of hydrops articuli observed by musculoskeletal ultrasound showed that 47 knees were cured, 19 knees improved and 2 knees failed. The synovial membrane thickness: 43 knees cured, 17 knees improved and 8 knees failed.</p><p><b>CONCLUSION</b>The hydrops articuli and synovial thickness of knee joint of patients with knee osteoarthritis observed under the MSUS is consistent with the main symptoms and signs, which suggests that MSUS observation on soft tissue changes before and after needle knife in the treatment of knee osteoarthritis with high reliability.</p>

Isolation, culture and intraspleenic transplantation of rat hepatic oval cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the evolution and differentiation of hepatic oval cells after transplanted into the spleens of homogenous rats, providing experimental data for treating hepatic failure with hepatic stem cells.</p><p><b>METHODS</b>A two-step perfusion procedure was used to separate hepatic parenchymal cells from nonparenchymal cells. Then the suspension of nonparenchymal cells was centrifuged in Percoll gradients. The isolated cells were cultured, identified, and then transplanted into the spleens of homogenous rats undergone 2/3 hepatectomy.</p><p><b>RESULTS</b>The obtained cells were various in size with ovoid nuclei and inadequate cytoplasm. After 12 hours' culture, they revealed the characteristics of epithelial cells. Both the freshly isolated and cultured cells showed positive staining for cytokeratin 19 (CK19), OV6, alpha fetal protein (AFP), but negative for leucocyte common antigen (LCA). After intraspleenic transplantation into homogenous rats undergone partial hepatectomy, hepatic oval cells were differentiated into liver tissue-like structure including hepatocyte cords and bile ducts, and formed hepaticized spleen. But this kind of structure was not observed in the controls.</p><p><b>CONCLUSION</b>The isolated rat hepatic oval cells show the biological characteristics of hepatic stem cells and can differentiate into hepatocytes and biliary epithelial cells under appropriate circumstances.</p>

Establishment and optimization of rat models for hepatic oval cells proliferation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish a rat model for hepatic oval cell proliferation and to observe the relationship between 2-acetaminofluorene (AAF) dosage and oval cell proliferation in the rat liver.</p><p><b>METHODS</b>Male Wistar rats weighing 150 g received daily oral gavage of AAF for 4 days before operation and up to 7 days after operation. Two-thirds hepatectomy was performed on the 5th day and the gavage was not performed on the day of operation. AFF was given with the dosage of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, and 20 mg/kg body weight. Animals in control group were given saline. Three rats from each group were killed every 2~3 days after hepatectomy and liver slices were fixed and processed for routine histology and immunohistochemistry.</p><p><b>RESULTS</b>Hepatic oval cells were not observed in the liver of controls and only a few were detected in the liver of 2.5 mg/kg and 5 mg/kg groups. However, obvious oval cell proliferation was seen in the liver of 10 mg/kg, 15 mg/kg, and 20 mg/kg groups. Hepatic oval cells were stained positive for cytokeratin 19, OV6, vimentin and proliferating cell nuclear antigen (PCNA).</p><p><b>CONCLUSIONS</b>Satisfactory rat models for hepatic oval cell proliferation can be obtained using our scheme when AAF is dosed at 10~20 mg/kg body weight.</p>