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Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the classic M1/M2 phenotypes, a number of novel dedifferentiation phenomena of TAMs are discovered due to the advanced single-cell technology, e.g., macrophage-myofibroblast transition (MMT) and macrophage-neuron transition (MNT). More importantly, emerging information demonstrated the potential of TAMs on cancer immunotherapy, suggesting by the therapeutic efficiency of the checkpoint inhibitors and chimeric antigen receptor engineered cells based on macrophages. Here, we summarized the latest discoveries of TAMs from basic and translational research and discussed their clinical relevance and therapeutic potential for solid cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ji, Chan, Chan, Leung, Jiang, To, Wu and Tang.)

In humans and animals, exposure to changes in internal or external environments causes acute stress, which changes sleep and enhances neurochemical, neuroendocrine, and sympathetic activities. Repeated stress responses play an essential role in the pathogenesis of psychiatric diseases and sleep disorders. However, the underlying mechanism of sleep changes and anxiety disorders in response to acute stress is not well established. In the current study, the effects of restraint stress (RS) on anxiety and sleep-wake cycles in mice were investigated. We found that after RS, the mice showed anxiety-like behavior after RS manipulation and increased the amounts of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in the dark period. The increase in sleep time was mainly due to the increased number of episodes of NREM and REM sleep during the dark period. In addition, the mice showed an elevation of the EEG power spectrum of both NREM and REM sleep 2 h after RS manipulation. There was a significant reduction in the EEG power spectrum of both NREM and REM sleep during the darkperiod in the RS condition. The expression of the c-Fos protein was significantly increased in the parabrachial nucleus, bed nucleus of the stria terminalis, central amygdala, and paraventricular hypothalamus by RS manipulation. Altogether, the findings from the present study indicated that neural circuits from the parabrachial nucleus might regulate anxiety and sleep responses to acute stress, and suggest a potential therapeutic target for RS induced anxiety and sleep alterations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Liu, Ji, Li, Wang, Wu, Liu, Ma, Zhong, Gao and Xu.)

Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2023.)

Lay Abstract: Autism spectrum disorder has long been conceptualized as a disorder of "atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions)." However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6-30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

Background: Autism spectrum disorder is characterized by atypical developmental changes during brain maturation, but regional brain functional changes that occur with age and across different frequency bands are unknown. Therefore, the current study aimed to explore potential age and frequency band-related changes in the regional brain activities in autism., Methods: A total of 65 participants who met the DSM-IV criteria for autistic disorder and 55 typically developed (TD) participants (both age 6-30 years) were recruited in the current study. The two groups were matched in age (t=-1.314, P=0.191) and gender (χ 2 =2.760, P=0.097). The amplitude of low-frequency fluctuations (ALFF) was employed to explore the effect of development on spontaneous brain activity in individuals with autism and in TD participants across slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and slow-3 (0.073-0.1 Hz) frequency bands. The diagnosis-by-age interaction effect in the whole brain voxels in autism and TD groups was investigated., Results: Autism individuals showed significantly higher ALFF in the dorsal striatum in childhood (Caudate cluster: t=3.626, P=0.001; Putamen cluster: t=2.839, P=0.007) and remarkably lower ALFF in the dorsal striatum in adulthood (Caudate cluster: t=-2.198, P=0.038; Putamen cluster: t=-2.314, P=0.030) relative to TD, while no significant differences were observed in adolescence (all P>0.05). In addition, abnormal ALFF amplitudes were specific to the slow-4 (0.027-0.073 Hz) frequency band in the clusters above., Conclusions: The current study indicated abnormal development patterns in the spontaneous activity of the dorsal striatum in autism and highlighted the potential role of the slow-4 frequency band in the pathology of autism. Also, the potential brain mechanism of autism was revealed, suggesting that autism-related variations should be investigated in a specific frequency., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-21-412/coif). The authors have no conflicts of interest to declare., (2022 Translational Pediatrics. All rights reserved.)

Background: Structural magnetic resonance imaging (sMRI) studies have shown atypicalities in structural brain changes in individuals with autism spectrum disorder (ASD), while a noticeable discrepancy in their results indicates the necessity of conducting further researches., Methods: The current study investigated the atypical structural brain features of autistic individuals who aged 6-30 years old. A total of 52 autistic individuals and 50 age-, gender-, and intelligence quotient (IQ)-matched typically developing (TD) individuals were included in this study, and were assigned into three based cohorts: childhood (6-12 years old), adolescence (13-18 years old), and adulthood (19-30 years old). Analyses of whole-brain volume and voxel-based morphometry (VBM) on the sMRI data were conducted., Results: No significant difference was found in the volumes of whole-brain, gray matter, and white matter between the autism and TD groups in the three age-based cohorts. For VBM analyses, the volumes of gray matter in the right superior temporal gyrus and right inferior parietal lobule in the autism group (6-12 years old) were smaller than those in the TD group; the gray matter volume in the left inferior parietal lobule in the autism group (13-18 years old) was larger than that in the TD group; the gray matter volume in the right middle occipital gyrus in the autism group (19-30 years old) was larger than that in the TD group, and the gray matter volume in the left posterior cingulate gyrus in the autism group was smaller than that in the TD group., Conclusion: Autistic individuals showed different atypical regional gray matter volumetric changes in childhood, adolescence, and adulthood compared to their TD peers, indicating that it is essential to consider developmental stages of the brain when exploring brain structural atypicalities in autism., (© 2022. The Author(s).)

Objective: To compare the value of new gastric cancer screening scoring system and serum pepsinogen (PG) combined with gastrin-17 (G-17) (new ABC method) in screening gastric cancer and precancerous lesions. Methods: A total of 576 patients were enrolled after the examination of endoscopy at Endoscopy Center,Department of Gastroenterology,from December 2017 to December 2019. There were 275 males and 301 females with an age of 40-72 (52±10) years. According to the new ABC method and the new gastric cancer screening scoring system, the population was divided into three groups according to age,gender,serum helicobacter pylori antibody test, PG Ⅰ/PG Ⅱ(PGR) and G-17 before endoscopy. The detection rates of gastric cancer and atrophic gastritis by two different methods were analyzed and the value in screening gastric cancer and precancerous lesions were evaluated. Statistical analysis was accomplished by Chi-square test and Gamma coefficient analysis. Results: A total of 576 patients were enrolled. According to the new ABC method, 382 patients were classified into low-risk group, 170 patients into middle-risk group and 24 patients into high-risk group, respectively. In the new ABC method, 1 case of gastric cancer (0.3%) was detected in low-risk group, 8 cases (4.7%) in middle-risk group and 3 cases (12.5%) in high-risk group. As for atrophic gastritis, 89 cases (23.3%) was detected in low-risk group, 94 cases (55.3%) in middle-risk group and 18 cases (75.0%) in high-risk group. According to the new gastric cancer screening scoring system, 336 patients were classified into low-risk group, 205 patients into middle-risk group and 35 patients into high-risk group, respectively. One case of gastric cancer (0.3%) was detected in low-risk group, 6 cases (2.9%) in middle-risk group and 5 cases (14.3%) in high-risk group. As for atrophic gastritis, 41 cases (12.2%) were detected in low-risk group, 134 cases (65.4%) in middle-risk group and 26 cases (74.3%) in high-risk group. In this two methods, the prevalence of gastric cancer increased according to the disease stage ( χ ² = 22.509, P <0.01; χ ²=24.156, P <0.01); in terms of atrophic gastritis, the detection rate of the new screening scoring system in the low-risk group was significantly lower than that in the new ABC method ( χ ²=14.844, P <0.01), but higher in the middle-risk group ( χ 2 =3.955, P =0.047). Gamma coefficient test showed that there were strong correlations between gastroscopy pathology and classification grade of both methods ( P <0.01). Conclusions: Both methods are suitable for screening gastric cancer and precancerous lesions, and the new scoring system may be more valuable in screening gastric cancer and precancerous lesions.

The transmembrane protease, serine 3 (TMPRSS3), a member of the type II transmembrane serine protease family, plays an important role in mediating tissue development, homeostasis and various biological processes. Recently, TMPRSS3 has been reported to be involved in cancer progression. However, the role of TMPRSS3 in gastric cancer (GC) remains largely unknown. In this study, we found that TMPRSS3 was highly expressed in GC tissues and cell lines. Knockdown of TMPRSS3 inhibited GC cell proliferation, invasion and epithelial-mesenchymal transition (EMT) in vitro as well as suppressed GC cell growth and dissemination in vivo. These inhibitory effects were mediated by regulation of the ERK1/2 signaling pathway. Moreover, TMPRSS3-mediated ERK1/2 activation was dependent on the PI3K/Akt pathway. In conclusion, TMPRSS3 contributed to GC progression via activation of the PI3K/Akt/ERK signaling pathway and might act as a therapeutic target for GC treatment., (Copyright © 2018. Published by Elsevier Masson SAS.)

Diabetic nephropathy (DN) is a severe renal disorder characterized by podocyte damage and accumulation of extracellular matrix leading to further glomerulosclerosis, possibly via the activation of inflammatory signaling and the generation of oxidative stress. Melatonin has been considered a robust anti‑oxidant, and is able to attenuate DN in several animal models. In the present study, cell viability was examined by CCK-8 assay. Cell apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential (MMP) levels were measured by flow cytometry. Western blot analysis was performed to detect the expression of Nephrin, B cell lymphoma‑2 (Bcl‑2)‑associated X protein (Bax), Bcl-2, Caspase-3, Janus kinase (JAK)2 and Signal transducer and activator of transcription (STAT)3 in podocytes. Based on an in vitro podocyte injury model, the present study found that the application of melatonin significantly reduced AngII‑induced apoptosis and increased the proliferative rate of cells, as evidenced by decreased expression levels of apoptotic proteins, including Caspase‑3 and Bax, and a change in the ratio of Bax/Bcl‑2. Further investigation demonstrated that a reduction in oxidative stress and the recovery of mitochondrial function were involved in this protective effect. In addition, the Jak/STAT signaling pathway was inhibited, indicating that cytokine‑mediated inflammation was also targeted by melatonin. The present study demonstrated for the first time, to the best our knowledge, that melatonin exerted an anti-apoptotic effect in AngII-mediated podocyte injury, and indicates a possible mechanism to explain the protective effect of melatonin in DN.

Aim: To evaluate the efficacy of centralized culture and possible influencing factors., Methods: From January 2010 to July 2012, 66452 patients with suspected Helicobacter pylori (H. pylori) infection from 26 hospitals in Zhejiang and Jiangsu Provinces in China underwent gastrointestinal endoscopy. Gastric mucosal biopsies were taken from the antrum for culture. These biopsies were transported under natural environmental temperature to the central laboratory in Hangzhou city and divided into three groups based on their transport time: 5, 24 and 48 h. The culture results were reported after 72 h and the positive culture rates were analyzed by a χ (2) test. An additional 5736 biopsies from H. pylori-positive patients (5646 rapid urease test-positive and 90 (14)C-urease breath test-positive) were also cultured for quality control in the central laboratory setting., Results: The positive culture rate was 31.66% (21036/66452) for the patient samples and 71.72% (4114/5736) for the H. pylori-positive quality control specimens. In the 5 h transport group, the positive culture rate was 30.99% (3865/12471), and 32.84% (14960/45553) in the 24 h transport group. In contrast, the positive culture rate declined significantly in the 48 h transport group (26.25%; P < 0.001). During transportation, the average natural temperature increased from 4.67 to 29.14 °C, while the positive culture rate declined from 36.67% (1462/3987) to 24.12% (1799/7459). When the temperature exceeded 24 °C, the positive culture rate decreased significantly, especially in the 48 h transport group (23.17%)., Conclusion: Transportation of specimens within 24 h and below 24 °C is reasonable and acceptable for centralized culture of multicenter H. pylori samples.

Concurrent garbage collectors (CGC) have recently obtained extensive concern on multicore platform. Excellent designed CGC can improve the efficiency of runtime systems by exploring the full potential processing resources of multicore computers. Two major performance critical components for designing CGC are studied in this paper, stack scanning and heap compaction. Since the lock-based algorithms do not scale well, we present a lock-free solution for constructing a highly concurrent garbage collector. We adopt CAS/MCAS synchronization primitives to guarantee that the programs will never be blocked by the collector thread while the garbage collection process is ongoing. The evaluation results of this study demonstrate that our approach achieves competitive performance.

Background: The exact mechanism of the effects of hypoxia on the proliferation and apoptosis in carcinoma cells is still conflicting. This study investigated the variation of hypoxia-inducible factor-1α(HIF-1α) expression and the apoptosis effect of hypoxia stimulated by cobalt chloride (CoCl(2)) in pancreatic cancer PC-2 cells., Methods: PC-2 cells were cultured with different concentration (50-200 μmol/L) of CoCl(2) after 24-120 hours to simulate hypoxia in vitro. The proliferation of PC-2 cells was examined by MTT assay. The cellular morphology of PC-2 cells were observed by light inverted microscope and transmission electron microscope(EM). The expression of HIF-1α on mRNA and protein level was measured by semi-quantitative RT-PCR and Western blot analysis. Apoptosis of PC-2 cells were demonstrated by flow cytometry with Annexin V-FITC/PI double staining., Results: MTT assay showed that the proliferation of PC-2 cells were stimulated in the first 72 h, while after treated over 72 h, a dose- dependent inhibition of cell growth could be observed. By using transmission electron microscope, swollen chondrosomes, accumulated chromatin under the nuclear membrane and apoptosis bodies were observed. Flow cytometer(FCM) analysis showed the apoptosis rate was correlated with the dosage of CoCl(2). RT-PCR and Western blot analysis indicated that hypoxia could up-regulate the expression of HIF-1α on both mRNA and protein levels., Conclusion: Hypoxic microenvironment stimulated by CoCl(2) could effectively induce apoptosis and influence cell proliferation in PC-2 cells, the mechanism could be related to up-expression of HIF-1α.

In the present study, we investigated the in vitro and in vivo antitumor effects of crude extract of Scutellaria Barbate (CE-SB) on mouse hepatoma H22 cells. The MTT assay was used to determine the growth inhibition of H22 cells in vitro. The in vivo therapeutic effects of CE-SB were determined using H22 tumor bearing mice. Besides, the body weight, tumor weight, thymus index and spleen index of H22 bearing mice were also measured. The tumor inhibitory rate (IR) was calculated according to the mean weight of tumor (MWT). The phagocytotic function of macrophages was examined by observing peritoneal macrophages phagocytize chicken RBC. The results showed that CE-SB could inhibit the growth of hepatoma H22 Cells in vitro and in vivo. Furthermore, CE-SB could improve immune function of H22 tumor bearing mice. Together these results indicate that CE-SB has antitumor activity and seems to be safe and effective for the use of anti-tumor therapy.

Background: Tumor necrosis factor (TNF)-α plays an important role in mediating inflammatory state in obesity and related disorders. Lipopolysaccharides (LPS)-induced TNF-α factor (LITAF) is recently verified as a regulator of TNF-α and other inflammatory cytokines, and maybe act as a transcriptional factor. The aim of this study was to confirm the association between LITAF and obesity and insulin resistance., Methods: Forty-seven subjects with a wide range of body mass index (BMI) were included. Subjects were divided into three groups according to the criteria of normal weight, overweight and obese. Anthropometrics and metabolic profile were tested for all the subjects. Peripheral monocytes were isolated and purified. LITAF transcription was detected by real time PCR, and the protein expression in whole cell and nucleus extracts was detected by Western blotting analysis; transcriptional activity of LITAF was detected by ELISA like assay using a probe containing the DNA binding sequence of LITAF. Plasma TNF-α and interleukin (IL)-6 concentrations were determined with ELISA kit., Results: The LITAF mRNA and protein expression in whole cell were higher in overweight (P < 0.05) and obese group (P < 0.05) compared with that in normal weight group. The LITAF protein expression in the nucleus and transcriptional activity could not be detected. LITAF protein expression was positively correlated with BMI (r = 0.541, P < 0.001), waist circumference (r = 0.391, P = 0.007), the homeostasis model assessment for insulin resistance (r = 0.372, P = 0.011) and fasting insulin levels (r = 0.359, P = 0.013). As a regulator of inflammatory cytokines, LITAF protein expression was positively correlated with plasma TNF-α (r = 0.621, P = 0.002) and IL-6 (r = 0.407, P = 0.039) concentration. Multiple variant regression analysis indicated that BMI (P = 0.002) and waist circumference (P = 0.017) were independent predictors of LITAF protein expression., Conclusions: LITAF is associated with obesity and insulin resistance, as well as inflammatory cytokine secretion. The results indicate LITAF to be a new mediator between inflammation and the obesity related disorders.

Objective: To investigate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of severe acute pancreatitis (SAP) in rats., Methods: Sixty-four male SD rats were randomly divided into control group and SAP group, and in the latter group, SAP was induced by retrograde injection of 5% sodium taurocholate in the pancreaticobiliary duct. The rats were sacrificed at 1, 3, 6 and 12 h after the operation, and the severity of pancreatitis was assessed according to histological scoring. The serum levels of VEGF were examined with enzyme-linked immunosorbent assay, and the expression of VEGF in the pancreatic tissues was measured by SP immunohistochemistry. Another 30 SD rats were randomized into the control group, SAP group and SAP+recombinant rat VEGF injection group, and the vascular permeability of the pancreatic microcirculation was determined by Evans Blue leakage test., Results: At each of the time points for measurement, both the serum VEGF level and scores of pancreatic tissue injury were significantly higher in SAP group than in the control group (P<0.05). Compared with the control group, the expressions of VEGF in the pancreatic tissues of SAP group were significantly up-regulated following the operation (P<0.05). The vascular permeability of the pancreatic microcirculation significantly increased after the onset of SAP, and injection of recombinant rat VEGF significantly increased the leakage rate of Evans Blue., Conclusion: VEGF may play an important role in the pathogenesis of pancreatitis and in causing edema and hemorrhage in SAP, and the level of serum VEGF may reflect the severity of pancreatic injury.

Objective: To investigate the protective effects of captopril against lung injury in a rat model of severe acute pancreatitis (SAP)., Methods: Seventy-two male SD rats were randomized into sham-operated group (SO group), SAP group and captopril intervention group (CAP group). Serum amylase and myeloperoxidase (MPO) activity in the lung tissue were examined at 1, 6 and 12 h after the operation. TNF-α and AngII in the lung tissue were detected by ELISA, and the histopathological changes of the pancreas and lung were observed microscopically., Results: The MPO activity , which was similar between SAP group and CAP group at 1 h, were significantly lowered in CAP group at 6 and 12 h (P<0.05). Serum amylase level and the levels of TNF-α and AngII in the lung tissue homogenate were all reduced significantly in CAP group as compared to those in SAP group (P<0.01). The pathological injury of the lung was obviously lessened in CAP group in comparison with that in SAP group., Conclusion: Captopril can ameliorate SAP-induced lung injury in rats.

Background: The aberrant activation of the Notch signaling has been associated with the development of colon cancers. However, the role of Notch1 in the pathogenesis of colon cancers is poorly understood., Methods: The expression of Notch1 in colon cancer tissues and nontumor tissues and in colon cancer cell lines was examined by Western blot analysis and immunohistochemistry. The impact of small interfering RNA (siRNA)-mediated Notch1 knockdown or Notch1 intracellular domain (NICD)-based transgene-induced Notch1 overexpression on the proliferation, cell cycling, apoptosis, colony formation, and tumorsphere formation in vitro and the development and growth of implanted tumors in vivo was characterized., Results: Notch1 was overexpressed in colon cancer tissues, and the levels of Notch1 expression in different types of colon cancers were associated with the pathologic grade, progression, and metastasis of colon cancers. Furthermore, knockdown of Notch1 significantly inhibited the proliferation, colony formation, and tumorsphere formation of SW480 and HT-29 cells, induced apoptosis and cell cycle arrest at G0/G1 phase, and mitigated the development and growth of implanted colon cancers in vivo. In contrast, Notch1 overexpression promoted the proliferation, colony formation, cell cycling, and tumorsphere formation of colon cancer cells in vitro and the development and growth of implanted colon cancers in vivo, but it inhibited spontaneous apoptosis., Conclusions: The current results indicated that Notch1 signaling positively regulates the growth of colon cancers. Conceivably, the modulation of Notch1-related signaling may be a promising therapy for human colon cancers., (Copyright © 2010 American Cancer Society.)

Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. We characterized the effects of selective CIAPIN1 inhibition on the angiogenesis gastric cancer cell line SGC7901 by stable transfection of CIAPIN1 siRNA. Our study has been shown that CIAPIN1 play the determined role in tumor growth and multidrug resistance. The conditioned media obtained from SGC7901 treated with CIAPIN1 siRNA suppressed in vitro the proliferation, migration and tube formation of human umbilical vein endothelial cells compared with untransfected cells or cells transfected with control vector alone. Furthermore, the stable transfection of CIAPIN1 siRNA inhibited in vivo tumorigenicity and angiogenesis. Our findings support that selective inhibition of CIAPIN1 alone plays an instrumental role on gastric cancer associated angiogenesis.

Aim of the Study: Matrine, an alkaloid purified from the chinese herb Sophora flavescens Ait, is well known to possess activities including anti-inflammation, anti-fibrotic and anticancer. In this study, the mechanism of matrine inducing the apoptosis of gastric carcinoma cells was investigated., Materials and Methods: Proliferation of SGC-7901 cells was examined by MTT assay. Cellular morphology was observed under transmission electron microscope. Flow cytometry (FCM) was used to observe the apoptosis of SGC-7901 cells by staining with annexinV-FITC/PI. The expression levels of Fas/FasL in SGC-7901 cells were monitored by FCM analysis using an indirect immunofluorescence method. Activity of caspase-3 enzyme was measured by spectrofluorometry., Results: MTT assay showed that matrine inhibited SGC-7901 cells proliferation in a dose-dependent and time-dependent manner. Apoptosis induction was demonstrated by morphological changes under electron microscope and FCM analysis. Fluorescence intensity levels of Fas and FasL were found to be equally up-regulated after matrine treatment, which were both correlated with apoptosis rate. The activity of caspase-3 enzyme increased in matrine groups, positively correlated with apoptosis rate., Conclusions: Matrine could inhibit cell proliferation and induce apoptosis of SGC-7901 cells in vitro. The apoptosis induction appears to proceed by up-regulating Fas/FasL expression and activating caspase-3 enzyme.

Objective: To investigate the inhibitory effects of Scutellaria barbate extracts on diethylnitrosamine-induced hepatocarcinoma in rats., Methods: Hepatocarcinoma model rats were induced by diethylnitrosamine (DEN). Sixty SD male rats were randomly divided into 4 groups: normal control group, hepatocarcinoma model group, ESB of high dose group and ESB of low dose group. All rats were killed in the 18th week, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), gamma-glutamyltransferase (gamma-GT) and alpha-L-fucosidase (AFU) in serum were measured by biochemical examinations; Hematoxy and eosin (HE) methods were used to examine the changes of liver pathology., Results: The levels of ALT, AST, TBIL, ALP, gamma-GT, AFU in hepatocarcinoma model group and ESB groups were higher than that of control group (P < 0.05). ESB could relieve hepatic injures. The levels of liver function indexes in ESB groups were lower than that of model group. Histological examination demonstrated that the number of liver cancer nodus in ESB groups were lower than that of model group. Furthermore, ESB could attenuate the grade of cancer cell differentiation., Conclusion: ESB could inhibit experimental hepatocarcinoma and relieve hepatic injures in rats.

Aim: To study the growth inhibitory and apoptotic effects of Scutellaria barbata D.Don (S. barbata) and to determine the underlying mechanism of its antitumor activity in mouse liver cancer cell line H22., Methods: Proliferation of H22 cells was examined by MTT assay. Cellular morphology of PC-2 cells was observed under fluorescence microscope and transmission electron microscope (EM). Mitochondrial transmembrane potential was determined under laser scanning confocal microscope (LSCM) with rhodamine 123 staining. Flow cytometry was performed to analyze the cell cycle of H22 cells with propidium iodide staining. Protein level of cytochrome C and caspase-3 was measured by semi-quantitive RT-PCR and Western blot analysis. Activity of caspase-3 enzyme was measured by spectrofluorometry., Results: MTT assay showed that extracts from S. barbata (ESB) could inhibit the proliferation of H22 cells in a time-dependent manner. Among the various phases of cell cycle, the percentage of cells in S phase was significantly decreased, while the percentage of cells in G(1) phase was increased. Flow cytometry assay also showed that ESB had a positive effect on apoptosis. Typical apoptotic morphologies such as condensation and fragmentation of nuclei and blebbing membrane of apoptotic cells could be observed under transmission electron microscope and fluorescence microscope. To further investige the molecular mechanism behind ESB-induced apoptosis, ESB-treated cells rapidly lost their mitochondrial transmembrane potential, released mitochondrial cytochrome C into cytosol, and induced caspase-3 activity in a dose-dependent manner., Conclusion: ESB can effectively inhibit the proliferation and induce apoptosis of H22 cells involving loss of mitochondrial transmembrane potential, release of cytochrome C, and activation of caspase-3.

Objective: To investigate the effects of Scutellaria barbata extract (ESB) in suppressing tumor growth and modulating the immune functions in mice bearing tumors derived from hepatocarcinoma H22 cells., Methods: Fifty mice inoculated subcutaneously with H22 cells were equally divided into the model group, high-, moderate-, and low-dose ESB groups, and 5-Fu group, with corresponding treatments for 10 days. Another 10 mice with only saline injection served as the normal control group. The body weight, tumor mass, thymus index and spleen index of the mice were measured, and the lymphocyte proliferation activity, NK cell activity and interleukin-2 (IL-2) production by the splenocytes were detected., Results: Moderate- and high-dose ESB significantly suppressed the tumor growth with tumor inhibition rate of 28.68% and 36.98%, respectively. ESB treatment at moderate and high doses significantly increased the thymus index and spleen index (P < 0.01), which were decreased significantly in 5-Fu group. The lymphocyte proliferation activity, NK cell activity and IL-2 production by the splenocytes were significantly lower in the model group than in the normal group (P < 0.05). Compared with the model group, ESB at the high dose obviously increased the three indexes above mentioned. The NK cell activity was also significantly improved in moderate-dose ESB group (P < 0.05)., Conclusion: ESB can suppress the growth of H22 implant tumor and enhance the immune function of the tumor-bearing mice.

Objective: To investigate the effects of serum containing Scutellaria Barbata extract (ESB) on apoptosis rate and mitochondrial transmembrane potential (MTP) of liver cancer cell line H22 from mice in vitro., Methods: H22 cells were cultured in vitro and divided into 5 groups: blank control group, low-dose ESB group, medium-dose ESB group, high-dose ESB group and fluorouracil (5-Fu) group. Methyl thiazolyl tetrazolium assay was utilized to determine the proliferation rates of H22 cells. Cellular morphology was observed under a transmission electron microscope (EM). The rhodamine 123 was used as a fluorescence probe to label the H22 cells, and the fluorescence intensities were observed with a laser scanning confocal microscope. The fluorescence intensity of H22 cells indicated the MTP of H22 cells., Results: The inhibition of serum containing ESB on the proliferation of H22 cells in vitro was observed in a time-dependent manner. The typical morphological changes of apoptosis were observed after incubation with ESB-containing serum in high dose for 48h. The apoptosis rates of blank control group, 5-Fu group, low-dose ESB group, medium-dose ESB group and high-dose ESB group were (0.51+/-0.32)%, (11.26+/-2.97)%, (1.07+/-0.46)%, (3.15+/-1.12)%, (7.83+/-2.25)% respectively. ESB could reduce the MTP of H22 cells from mice as compared with the untreated group. The MTPs of the blank control group, 5-Fu group, and low-, medium- and high-dose ESB groups were (245.45+/-67.37), (127.42+/-41.35), (213.68+/-65.52), (186.34+/-56.37) and (142.65+/-39.44) respectively, which were negatively correlated with the apoptosis rates., Conclusion: ESB-containing serum effectively induces apoptosis, which may be related to the decrease of MTP in H22 cells.

Objective: To study the assistant effect of Scutellaria barbata extract (ESB) in 5-fluorouracil (5-FU) chemotherapy., Methods: A mouse model of transplanted hepatoma H22 was used in this study to evaluate the synergic and attenuating effects of ESB in chemotherapy. Tumor inhibition rate, life span of mice and the toxicity of chemotherapy were observed. The body weight, tumor weight, thymus index and spleen index in H22-bearing mice were also measured. The phagocytotic function of macrophages was studied by observing phagocytization of peritoneal macrophages., Results: The increase of body weight in 5-FU plus ESB groups was higher than that in 5-FU group, and the side effects such as anorexia, abdominal distention and athrepsy were relieved. Compared with untreated group, prolonged lifetime in 5-FU plus high-dose ESB group and 5-FU plus low-dose ESB group was improved. Life prolongation rates in 5-FU plus high-dose ESB group and 5-FU plus low-dose ESB group were 61.46% and 23.59% respectively. High-dose ESB, 5-FU, 5-FU plus low-dose ESB and 5-FU plus high-dose ESB could inhibit the tumor growth, and the tumor inhibition rates were 36.98%, 42.26%, 52.45% and 65.28%, respectively. Thymus index and spleen index were increased significantly in 5-FU plus low-dose ESB group and 5-FU plus high-dose ESB group. White blood cell (WBC) count was decreased obviously in 5-FU group, while the count of WBC was increased in 5-FU plus low-dose ESB group and 5-FU plus high-dose ESB group. The phagocytotic function of macrophages was also increased in 5-FU plus low-dose ESB group and 5-FU plus high-dose ESB group., Conclusion: ESB can enhance the effect of chemotherapy, relieve the side effects and improve immune function of mice in chemotherapy. These results suggest that ESB, as a biochemical modulator to enhance the therapeutic effects, is useful in cancer chemotherapy.

Objective: To investigate the mechanism of gastric carcinoma cells apoptosis induced by matrine injection in vitro., Methods: Effects of 24, 48, 72, 96 h incubation with different concentrations (0.25-1.5 g/L) of matrine injection on proliferation of SGC-7901 cells were evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The cellular morphology of SGC-7901 cells was observed by transmission electron microscope (EM). Flow cytometry was used to analyze the apoptosis of SGC-7901 cells by staining with annexin V-FITC/PI. The expression of Fas/FasL was examined by flow cytometry using specific antibody. The activity of caspase-3 was measured by spectrofluorometry., Results: Matrine injection could inhibit the proliferation of SGC-7901 cells in a dose- and time-dependent manner. The typical morphological changes of apoptosis were observed after incubation with 1.0 g/L matrine injections for 48 h. The apoptosis rates of 0.5 g/L, 1.0 g/L and 1.5 g/L groups were 39.80%, 58.11% and 79.00% respectively. The apoptotic cells in matrine injection group were mainly early apoptotic cells, and those in 5-FU group were mainly late apoptotic cells and necrotic cells. Spectrofluorometry revealed FI levels of Fas and FasL were equal, which were both correlated with apoptosis rate. The activity of caspase-3 increased with the elevation of matrine concentration, and was correlated with the apoptosis rate., Conclusion: Matrine injection can induce apoptosis of SGC-7901 cells through the up-regulation of Fas/FasL expression and activation of caspase-3.

Objective: To investigate the effects of Scutellaria barbate extract (ESB) on suppressing proliferation and inducing apoptosis of mouse hepatoma H22 cells., Methods: H22 cells cultured in vitro were divided into 5 groups: blank control group, ESB in high, medium, low dose groups and 5-Fu group. H22 cells were cultured in media with serum containing different concentrations of ESB and blank serum. The proliferation of H22 cells was determined by microculture tetrazolium (MTT) assay. Fluorescence microscopy was utilized to observe the apoptosis of H22 cells by staining with Hoechst 33258. The cell cycle and apoptosis were analyzed by flow cytometry (FCM)., Results: The inhibition of serum containing ESB on the proliferation of H22 cells in vitro was observerd in a dose and time dependent manner. The typical morphological changes of apoptosis were observed after incubation with ESB-containing serum in high dose for 48 hours. Among the various phases of cell cycle, the percentage of cells in S phase decreased significantly, while the percentage of cells in G1 phase increased. Drug-containing serum showed positive effect on cell apoptosis. The apoptosis rate of blank control group, ESB in low, medium, high dose groups and 5-Fu group were 0.51%, 1.07%, 3.15%, 7.83%, 11.26%, respectively., Conclusion: ESB containing serum can inhibit proliferation and induce apoptosis of H22 cells in vitro.

Objective: To investigate the effects of alprostadil (Lipo PGE1) in prevention of portal vein thrombogenesis (PVT) after splenectomy for portal hypertension., Methods: Seventy-six patients with portal hypertension undergoing splenectomy and pericardial devascularization were randomly divided into 2 groups :treatment group (n = 40), receiving intravenous drip of injection of radix Salviae miliorrhazae (RSM) 40 ml and alprostadil 20 microg, both once a day since the third day after operation for 2 weeks and then oral administration of dropping pill of SM, and control group (n = 36), receiving intravenous drip of injection of RSM and taking enteric coated aspirin 3 times a day for 2 weeks and then taking dropping pill of SM. Platelets (PLT), prothrombin time (PT), and liver function were detected periodically. Color Doppler ultrasonography was conducted every week to observe the blood flow velocity and diameter of the portal and splenic veins, and if PVT event and ascites occurred. All patients were followed up for 8 - 20 months., Results: No prolongation of coagulation time and bleeding tendency was found in both groups. The PLT number increased remarkably in the 7th to 14th days after operation without significant difference between the 2 groups (P >0.05). The PVT rate of the treatment group was 5.0%, significantly lower than that of the control group (25.0%, chi2 = 6.12, P < 0.05). The ascites rate of the treatment group was 10.0%, significantly lower than that of the control group (33.3%, chi2 = 7.44, P <0.01). The levels of ALT and total bilirubin 7 and 16 days after operation of the treatment group were all significantly lower than those of the control group (all P <0.05)., Conclusion: Use of alprostadil early after devascularization is an effective and safe measure to prevent PVT, improve liver function, and decrease ascites rate.

Objective: To study the therapeutic effects of recombinant adeno-associated virus (rAAV) expressing fusion peptide NT4p53(C22)Ant against transplanted liver cancer in ICR mice., Methods: NT4p53(C22)Ant was constructed, subcloned into recombinant AAV vector, and amplified in 293 packaging cells. The efficacy of rAAV-NT4p53(C22)Ant on tumors derived from H22 cells inoculated subcutaneously in IRC mice was evaluated according to the tumor weight, inhibition rate, survival time of the mice and the histological findings., Results: A single dose of rAAV-NT4p53(C22)Ant of 100 microl (2 x 10(11) pfu/ml) injected into the transplanted H22 tumors in the ICR mice resulted in tumor disappearance in 7 (totally 12) mice, and death occurred in only 1 mouse. The injection also resulted in decreased tumor weight and prolonged survival of the mice (for over 70 days). All the 7 mice with only rAAV injection or no treatment all died, with a mean survival of about 30 days. The tumor inhibition rate exceeded 90% in mice with rAAV-NT4p53(C22)Ant injection, significantly higher than that of mice without the injection. The histological examination revealed significantly decreased tumor cells in mice with rAAV-NT4p53(C22)Ant injection as compared with those without such treatment., Conclusion: rAAV-NT4p53(C22)Ant can induce apoptosis of the H22 tumor cells transplanted in IRC mice to inhibit the tumor growth and prolong the survival of the mice.

Background: In the mouse skin allograft model, specific immune tolerance to the donor was induced by injection of donor hepatic non-parenchymal cells (NPCs). This markedly prolonged the survival time of the allograft. The mechanism of the induction of immune tolerance with donor hepatic NPCs is thought to be related to microchimerism and the IL-4 level. This work aimed at exploring the way of inducing immune tolerance and understanding the mechanism., Methods: C57BL/6 (B6) mice were primed by intravenous injection of 2 x 10(7) NPCs from C3H mice. Cyclophosphamide (200 mg/kg) was injected intraperitoneally 48 hours later. Eighteen days after the NPC injection, skin from C3H mice was transplanted to B6 mice and the survival of the grafts was assessed. The immune reaction of splenocytes from the treated B6 mice to donor-specific T-cells was measured by 3H-TdR incorporation. Microchimerism in the spleen was determined by flow cytometric analysis sytem (FCAS) analysis, and the serum level of IL-4 was assayed by ELISA at designed times., Results: The survival time of the skin graft was markedly prolonged from 10 days to 70 days in controls. Microchimerism in the spleen was found as early as day 1 post-NPC injection, then it increased steadily, and there was a positive relationship between graft survival and the quantity of microchimerism. The ELISA results showed that NPC infusion enhanced IL-4 production, especially in the mice with longer graft survival., Conclusion: Donor NPC infusion pre-transplant can prolong the survival of the skin graft and microchimerism and high levels of IL-4 may be involved.

Objective: To investigate the effects of antisense oligonucleotide specific to K-ras point mutation on human pancreatic carcinoma cell PC-2 in vitro., Methods: Human pancreatic carcinoma cell PC-2 was transducted with antisense oligonucleotide specific to K-ras point mutation by liposome; the expression of target gene was studied with immunohistochemistry and in situ hybridization. The effect on cell proliferation was studied by artificial count, MTT and mass test., Results: The expression degree of ras protein and K-ras mRNA transducted with antisense oligonucleotide decreased apparently compared with control group and sense oligonucleotide group 48 h after tansduction. The inhibitory effect on cell proliferation was confirmed by artificial count, MTT and mass test., Conclusions: Antisense oligonucleotide specific to K-ras point mutation has an apparent inhibitory effect on target gene expression and cell proliferation of human pancreatic carcinoma cell in vitro.

Objective: To investigate the role of Ras antisense oligoribonucleotide (ASODN) in multidrug resistance (MDR) of pancreatic carcinoma Pc-2 cells., Methods: Ras and P-gp expression was suppressed by Ras ASODN. Sensitivity of Pc-2 cells to chemotherapy was determined by the MTT assay. MDR-1 mRNA level was detected by fluorogenic probe quantitative reverse transcription polymerase chain (RT-PCR) method. Flow cytometry (FCM) was used to detect the accumulative concentration of adriamycin (ADR) in the cells., Results: Ras ASODN significantly inhibited the Ras and P-gp expression (P < 0.05), increased the sensitivity of Pc-2 cells to chemotherapeutic agents (P < 0.05), decreased MDR-1 gene level in Pc-2 cells (P < 0.05), and increased the intracellular intake of ADR in Pc-2 cells (P < 0.05)., Conclusion: Ras ASODN may enhance the sensitivity of multidrug-resistant pancreatic cancer Pc-2 cells to chemotherapeutic agents by regulating MDR-1 gene level.

Objective: To assess the value of ultrasound in diagnosis of congenital renal malformations., Methods: The records of obstetric ultrasound examinations were reviewed in all the pregnant women admitted in Alta Bates Perinatal Diagnostic center (Oakland, California, USA) during 5 years., Results: Ultrasound examination identified 58 cases of congenital renal malformations of different kinds, including 4 cases of renal agenesis, 8 multicystic dysplastic kidney, 5 cystic renal dysplasia with obstructions, 6 renal and ureteral duplications, 6 ectopic kidneys, 18 hydronephroses, 3 autosomal recessive polycystic kidney diseases, 2 autosomal dominant polycystic diseases, 1 Finnish-type congenital nephrosis, 3 Meckel-Gruber syndromes, and 2 Beckwith-Wiedemann syndromes. Different renal malformations had different ultrasound findings that correlated to abnormalities in embryonic developments., Conclusions: Urinary tract abnormalities have a profound effect on pregnancy outcome, especially when associated with oligohydramnios. Many urinary anomalies can be readily detected and diagnosed by ultrasound, which provides a useful modality in diagnosis of fetal congenital renal malformations. Clear understanding of the causes of these abnormalities facilitates prognostic evaluation and clinical decision on the treatment protocol.

Aim: To investigate the effect of antisense oligodeoxynucleotides (ASODN) targeting Pim-2 on cell proliferation of DU-145 cells., Methods: Three ASODN targeting Pim-2 were designed and synthesized. After transfection with ASODN, cell proliferation was analyzed using an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. In addition, Pim-2 mRNA, protein levels, and cell cycles were examined., Results: The ASODN designed and synthesized by our laboratory significantly reduced Pim-2 mRNA level and protein content in DU-145 cells. After transfection with ASODN for 48 h, a marked reduction in cell viability was observed in DU-145 cells in a dose-dependent manner. No remarkable apoptosis occurred in cells treated with ASODN compared with control cells. However, it should be noted that G1 phase arrest was clearly observed in ASODN-treated cells., Conclusion: ASODN targeting Pim-2 resulted in a marked reduction in DU-145 cell proliferation, and induction of G1 phase cell cycle arrest is one of the important mechanisms for ASODN to reduce cell growth. Moreover, antisense inhibition of Pim-2 expression provides a new promising therapy target for prostate cancer.

Aim: To explore the effect of hypertonic saline on the erythrocyte adherence function and bacterial infection of hemorrhagic shock rabbits., Methods: 60 Japanese rabbits were randomly divided into 6 groups, 10 for each group. Artery catheterization and heparin were given to the rabbits in group 1 (sham shock group). Hemorrhagic shock model was set up by bleeding resulting from carotid artery catheter in group 2 (normal saline group )and group 3 (hypertonic saline group). 30 minutes after shock, the rabbits in group 1 and group 2 were treated with normal saline and balanced salt solution containing 1 x 10(9)/kg E.coli, respectively. And the rabbits in group 3 were treated with 75 g/L NaCl solution and balanced salt solution containing 1 x 10(9)/kg E.coli. Then the survival rates of the rabbits in group 1-3 were observed. Rabbits in group 4-6 were same treatment as received, group 1-3, respectively, except that there was no E.coli in balanced salt solution. The erythrocyte immune adherence function of rabbits in group 4-6 were detected 5 hours after shock by RBC-C3bR and RBC-IC rosette forming assays., Results: The survival rate of rabbits in hypertonic saline group was significantly higher than that in normal saline group. The RBC-C3bR rosette forming rate of the normal saline treated rabbits were pronouncedly decreased, while RBC-IC rosette forming rate was notably elevated, as compared with those of either sham shock group or hypertonic saline group(P<0.01). Hypertonic saline markedly increased RBC C3bR rosette forming rate., Conclusion: The above findings suggest that hypertonic salt solution can remarkably improve the depressed erythrocyte immune adherence function and enhance the rabbit's resistance to E.coli challenge after hemorrhagic shock.

Aim: To synthesize three small-interference RNAs (siRNAs) by T7 RNA polymerase-catalyzed reaction, and to investigate their efficacy on modulating the expression of serine/threonine kinase Pim-2 in human colon cancer cell line., Methods: siRNA I, II and III were synthesized by T7 RNA polymerase-directed in vitro transcription, then transfected into human colon cancer cells SW-480. After incubation for 6 h at 37 degrees, 100 mL/L FBS in RPMI 1640 was substituted in each well. After the transfection was repeated twice to three times in each kind of siRNA, hPim-2 mRNA and protein expression were measured by RT-PCR and Western blotting, respectively., Results: Compared to the control group, after transfected for 48 h with hPim-2 siRNA I, II and III, the relative inhibition rates of hPim-2 mRNA expression in colon cancer cells were 65.4% (P<0.05), 46.2% (P<0.05) and 56.1% (P<0.05), respectively. The protein level of hPim-2 was decreased at 72 h compared to the untransfected cells. The relative inhibition percentages of hPim-2 protein by siRNA I, II, III were 61.6% (P<0.05), 45.8% (P<0.05) and 55.6% (P<0.05), respectively., Conclusion: The in vitro transcribed siRNAs can be useful for silencing oncogene hPim-2 expression specifically and efficiently. This may open a new path toward the use of siRNAs as a gene-specific therapeutic tool.

Aim: To study the anti-inflammatory activity of N-(4-arylamidophenyl) methanesulfonamide derivatives., Methods: The target compounds were synthesized from p-nitroaniline via three steps and were evaluated for anti-inflammatory activity with the model of xylene-induced ear edema in mice., Results: Eleven compounds were obtained and confirmed by IR, 1HNMR and MS. Some compounds were shown to have significant anti-inflammatory activity., Conclusion: N-(4-arylamidophenyl) methanesulfonamide showed appreciable anti-inflammatory activity.

Background & Objective: Survivin is one of the newly identified apoptosis inhibitor; it can block the cell apoptosis by inhibiting the function of the enzyme caspase-3 and caspase-7. Present studies indicate that survivin is overexpressed in malignant tumor. This current study was designed to investigate the effects of survivin in tumorigenesis and progression of breast carcinoma through observing the expression of survivin in the tissue of normal mammary, cystic hyperplasia mammary, atypical hyperplasia mammary and breast carcinoma., Methods: The expression of survivin in the tissue of normal mammary (96 cases), cystic hyperplasia mammary (56 cases), atypical hyperplasia mammary (12 cases), and breast carcinoma (119 cases) were evaluated by SP immunohistochemistry. The relationship between survivin expression and the pathologically biological features of breast cancer was assessed., Results: The positive rates of survivin were 4.2%(4/96),5.4% (3/56),42.7% (5/12), and 72.3%(86/119)in the tissue of normal mammary, cystic hyperplasia mammary, atypical hyperplasia mammary, and breast carcinoma, respectively. The positive rates in the last two groups were higher than those in the former two groups (P< 0.005). Survivin was more expressed in the infiltrative nonspecial breast carcinoma (82.0%, 73/89) than in the special and early stage infiltrative breast carcinoma (37.5%,3/8)(P< 0.05). Expression of survivin was correlated with lymph node metastasis although the difference is not significant (P >0.05)., Conclusion: Overexpression of survivin is common in tumorigenesis and progression of breast carcinoma. Altered expression of survivin may contribute to tumorigenesis and progression of breast carcinoma by inhibiting cell apoptosis, its overexpression indicates worse prognosis.

As part of a national rotavirus surveillance activity, we collected fecal specimens from 3,177 children with acute diarrhea in 10 regions of China between April 1998 and April 2000 and screened them for rotavirus. Rotavirus was detected in 41% (n = 1,305) of specimens, and in these, G1 was the predominant serotype (72.6%), followed by G3 (14.2%), G2 (12.1%), G4 (2.5%), G9 (0.9%), and G untypeable (0.7%). Among 327 G-typed strains tested for P genotype, 14 different P-G combinations were identified, with the globally common strains P[8]G1, P[4]G2, P[8]G3, and P[8]G4 representing 75.6% of all typed rotavirus strains. Among the uncommon strains, 11 were P[6]G9, and others included P[6]G1, P[6]G3, and five novel P-G combinations (P[9]G1, P[4]G1, P[4]G3, P[4]G4, and P[8]G2). Our results indicate that while the common rotavirus strains remain predominant, the diversity of strains is much greater than was previously recognized.

247 liver transplantations in 210 patients were done between June 1983 and April 1991 in our hospital. In this paper we have analyzed our experience with adult liver transplantation from the view point of quality of life after liver transplant. Indications for liver transplantation were the following: 46 patients with cirrhosis due to non A, non B hepatitis, 29 with alcoholic cirrhosis, 13 with hepatitis B, 34 with primary biliary cirrhosis, 26 with primary sclerosing cholangitis, 29 with acute hepatic necrosis, 10 with liver tumor, 13 with miscellaneous other diseases. Of the 210 patients, 125 are alive to date. One, three and five year survival rates (excluding perioperative death) of all patients were 80.2%, 70.6% and 65.45% respectively. The best rehabilitation is in 73 patients who are full time workers or full time students and in 16 patients who are homemakers. The degree of rehabilitation in these patients is very high: 6 patients died after achieving complete rehabilitation; 11 patients retired from employment after liver transplantation; 8 patients are chronically disabled; 79 patients died before rehabilitation could be achieved. Rehabilitation rates of one and five year survivors are 78% and 84.2% respectively. Quality of life has been satisfactory following liver transplantation.

Cinnamic acids were selected as lead compounds of antiinflammatory and anticancer agents through the investigation of their biological properties. Their esters and related styryl ketones were also studied. A total of nineteen compounds, fifteen of them not reported previously, were synthesized and found to be of considerable pharmacological interest. In preliminary biological tests, compounds IA, IB, IC, II2C and II5C showed significant inhibiting effect on croton oil induced mouse ear edema, IB, II5A, II5C and IIID exhibited good activity on HL-60 human cancer cells in vitro. It is well worth noticing that compounds IB and II5C exhibited excellent antiinflammatory action as well as anticancer activity.

It has been known that non-steroidal antiinflammatory drugs (NSAIDs) act by preventing cyclooxygenase products of arachidonic acid. In recent years, research on non-steroid dual inhibitors of cyclooxygenase (CO) and 5-lipoxygenase (5-LO), which should represent a novel class of antiinflammatory drugs with a wider spectrum of activity than classical NSAIDs, has been carried out. In the present paper, a total of 29 compounds including 18 compounds of 2-(E)-(un) substituted benzylidene cyclopentanone (I) derivatives and 11 compounds of 2-(E)-(un)substituted benzylidene-5-dimethylaminomethyl cyclopentanone (II) derivatives were synthesized as dual inhibitors of CO/5-LO. Preliminary pharmacological test showed that I4, I12 and I13 given orally have significant inhibiting effect on carrageenan induced rat paw edema and most compounds of type II exhibited potent effect when given subcutaneously. In particular, II3, which inhibited by 95.8%, 70.34%, and 44.2% at 50, 25, and 12.5 mg/kg respectively, was similar to Ibuprofen. Some compounds of type II exhibited anticancer activity both in vitro (IC50 ranging from 2.93 to 18.06 mumol/L on L1210) and in vivo (maximum increase of life span was 97.5% on EAC in mice).

The aim of this study was to increase the stability of WB852 in aqueous solution by inclusion complex formation with beta-cyclodextrin (beta-CD). The stability of WB852-beta-CD in aqueous solution was determined. The hydrolysis rate of WB852 from the inclusion compound was lower than that of WB852 alone. The solid inclusion compound of WB852 with beta-CD in 1:3 molar ratio was prepared by the freeze-drying method. The formation of an inclusion compound with beta-CD in solid state was confirmed by X-ray diffractometry, IR spectroscopy and differential thermal analysis (DTA).