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Background: Reliable prediction of progression patterns and failure sites for patients with stage IV lung adenocarcinoma is valuable for physicians to deliver personalized tyrosine kinase inhibitor (TKI) treatment., Patients and Methods: We retrospectively enrolled 266 patients who had stage IV lung adenocarcinoma and received first-line TKI treatment from 2013 to 2017 in Shanghai Chest Hospital. The clinical characteristics at initial diagnosis, progression patterns, and failure sites were analyzed with the attempt to identify some predictive factors for progression patterns and failure sites., Results: Among all patients, 62.4% developed systemic progression, and 37.6% developed oligoprogression. Both cohorts had a median progression-free survival (PFS) of 9 months. The percentage of patients who developed original and distant failure was 39.1% and 60.9%, respectively. Patients with oligometastasis at initial diagnosis were more prone to develop oligoprogression (odds ratio [OR], 4.370; 95% confidence interval [CI], 1.881-10.151; P = .001), whereas pulmonary metastasis was negatively correlated with oligoprogression (OR, 0.567; 95% CI, 0.330-0.974; P = .04). Both oligometastasis diagnosis (OR, 2.959; 95% CI, 1.347-6.500; P = .007) and the maximum diameter of the primary lung lesion (threshold 3.25 cm: OR, 3.646; 95% CI, 2.041-6.515; P = .0001) were strong predictive factors for original failures. Osseous metastasis at initial diagnosis might be an indication for distant failure (OR, 0.536; 95% CI, 0.316-0.909; P = .021)., Conclusion: Over one-half of patients with stage IV lung adenocarcinoma receiving first-line TKI treatment developed systemic progression and distant failure. Metastasis patterns at initial diagnosis was the most important predictive factor for progression patterns and failure sites. The maximum diameter of the primary lung lesion and evidence of osseous metastasis were also found to be significant indicative factors for failure sites., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Chlorpyrifos (CPF) is a organophosphate insecticide widely used in agriculture with attendant adverse health outcomes. Chronic exposure to CPF induces oxidative stress and elicits harmful effects, including hepatic dysfunction. Molecular hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals., Objective: The aim of this study was to determine whether the intake of hydrogen-rich water (HRW) could protect rats from hepatotoxicity caused by sub-chronic exposure to CPF., Material and Methods: Rats were treated with hydrogen-rich water by oral intake for 8 weeks. Biochemical indicators of liver function, SOD and CAT activity, GSH and MDA levels were determined by the spectrophotometric method. Liver cell damage induced by CPF was evaluated by histopathological and electron microscopy analysis. PCR array analysis was performed to investigated the effects of molecular hydrogen on the regulation of oxidative stress related genes., Results: Both the hepatic function tests and histopathological analysis showed that the liver damage induced by CPF could be ameliorated by HRW intake. HRW intake also attenuated CPF induced oxidative stress, as evidenced by restored SOD activities and MDA levels. The results of PCR Array identified 12 oxidative stress-related genes differentially expressed after CPF exposure, 8 of chich, including the mitochondrial Sod2 gene, were significantly attenuated by HRW intake. The electron microscopy results indicated that the mitochondrial damage caused by CPF was alleviated after HRW treatment., Conclusions: The results obtained suggest that HRW intake can protect rats from CPF induced hepatotoxicity, and the oxidative stress signaling and the mitochondrial pathway may be involved in the protection of molecular hydrogen.

Background: It has been reported the rs10757274 SNP (present on locus 9p21 in the gene for CDKN2BAS1) might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to investigate the association between rs10757274 polymorphism and the risk of CAD., Objectives: The present study aimed to investigate the relationship between rs10757274 polymorphism and the risk of CAD., Methods: All studies of the rs10757274 SNP with CAD that were published between 2007 and 2018 were retrieved from the PubMed database. Meta-analysis was performed with Stata 14.0 software. The effect size of the rs10757274 SNP with CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI)., Results: Eleven studies including 52,209 subjects (cases: 7990, controls: 44,219) were included in the final data combination. Pooled overall analyses showed that rs10757274 (allele model: P < .001; dominant model: P < .001; recessive model: P < .001; Heterozygote codominant: P = .002; Homozygote codominant: P < .001) polymorphisms were significantly associated with the likelihood of CAD. Significant heterogeneity between individual studies appears in all 5 models. Further subgroup analyses revealed that rs10757274 polymorphisms were all significantly correlated with the likelihood of CAD and no heterogeneity were observed in West Asians., Conclusions: Our findings indicated that rs10757274 polymorphisms may serve as genetic biomarkers of CAD, especially in West Asians.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether ginsenoside Rg1, a ginseng-derived compound, could prevent chemobrain and its underlying mechanisms. A mouse model of chemobrain was developed with three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination at a 2-day interval. Rg1 (5 and 10 mg/kg daily) was given 1 week prior to DAC regimen for 3 weeks. An amount of 10 mg/kg Rg1 significantly improved chemobrain-like behavior in water maze test. In vivo neuroimaging revealed that Rg1 co-treatment reversed DAC-induced decreases in prefrontal and hippocampal neuronal activity and ameliorated cortical neuronal dendritic spine elimination. It normalized DAC-caused abnormalities in the expression of multiple neuroplasticity biomarkers in the two brain regions. Rg1 suppressed DAC-induced elevation of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but increased levels of the anti-inflammatory cytokines IL-4 and IL-10 in multiple sera and brain tissues. Rg1 also modulated cytokine mediators and inhibited DAC-induced microglial polarization from M2 to M1 phenotypes. In in vitro experiments, while impaired viability of PC12 neuroblastic cells and hyperactivation of BV-2 microglial cells, a model of neuroinflammation, were observed in the presence of DAC, Rg1 co-treatment strikingly reduced DAC's neurotoxic effects and neuroinflammatory response. These results indicate that Rg1 exerts its anti-chemobrain effect in an association with the inhibition of neuroinflammation by modulating microglia-mediated cytokines and the related upstream mediators, protecting neuronal activity and promoting neuroplasticity in particular brain regions associated with cognition processing.

Objective: Berberine (BBR) clinically lowers blood lipid and glucose levels via multi-target mechanisms. One of the possible mechanisms is related to its effect on the short chain fatty acids (SCFAs) of the gut microbiota. The goal of this study is to investigate the therapeutic effect and mode of action of BBR working through SCFAs of the gut microbiota (especially, butyrate)., Methods: Gas chromatography (GC) was used to detect butyrate and other SCFAs chemically. The effect of BBR on butyrate production was investigated in vitro as well as in several animal systems. Microarrays were used to analyze the composition change in the intestinal bacteria community after treatment with BBR. BBR-induced change in the energy production and gene regulation of intestinal bacteria was examined in order to elucidate the underlying molecular mechanisms., Results: We show that oral administration of BBR in animals promoted the gut microbiota to produce butyrate, which then enters the blood and reduces blood lipid and glucose levels. Incubating gut bacterial strains in vitro with BBR increased butyrate production. Orally treating animals directly with butyrate reduced blood lipid and glucose levels through a mechanism different from that of BBR. Intraperitoneal BBR administration did not increase butyrate but reduced blood lipid and glucose levels, suggesting that BBR has two modes of action: the direct effect of the circulated BBR and the indirect effect working through butyrate of the gut microbiota. Pre-treating animals orally with antibiotics abolished the effect of BBR on butyrate. A mechanism study showed that BBR (given orally) modified mice intestinal bacterial composition by increasing the abundance of butyrate-producing bacteria. Furthermore, BBR suppressed bacterial ATP production and NADH levels, resulting in increased butyryl-CoA and, eventually, butyrate production via upregulating phosphotransbutyrylase/butyrate kinase and butyryl-CoA:acetate-CoA transferase in bacteria., Conclusion: Promotion of butyrate (etc) production in gut microbiota might be one of the important mechanisms of BBR in regulating energy metabolism., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical coupling between neocortical excitatory neurons is critical for proper neuronal development, synapse formation, and animal behavior. Conditional deletion of Connexin 26 ( CX26 ) in the superficial layer excitatory neurons of the mouse neocortex around birth significantly reduces spontaneous firing activity and the frequency and size of spontaneous network oscillations at postnatal day 5-6. Moreover, CX26 -conditional knockout ( CX26 -cKO) neurons tend to have simpler dendritic trees and lower spine density compared with wild-type neurons. Importantly, early, but not late, postnatal deletion of CX26 , decreases the frequency of miniature excitatory postsynaptic currents (mEPSCs) in both young and adult mice, whereas miniature inhibitory postsynaptic currents (mIPSCs) were unaffected. Furthermore, CX26 -cKO mice exhibit increased anxiety-related behavior. These results suggest that electrical coupling between excitatory neurons at early postnatal stages is a critical step for neocortical development and function.

Objective To observe the clinical efficacy of Guishen Zhiyang Recipe (GZR) in trea- ting senile pruritus patients with blood deficiency and hyperactivity of Gan-yang syndrome (BDHGYS) and to study the mechanism in nervous-endocrine-immune systems. Methods Ninety senile pruritus pa- tients were assigned to the treatment group and the control group by complete randomized lot, 45 in each group. Totally 41 patients in the treatment group and 38 patients in the control group completed the trial. Patients in the treatment group took GZR, while those in the control group took Fuyang Granule (FG). Ex- ternal application of Binghuang Fule Soft Ointment was performed to all patients. The therapeutic course for all was 8 weeks. Symptoms and efficacy changes in skin lesion were observed in the two groups. Lev- els of stem cell factor (SCF) , dynorphin (DYN) , testosterone (T) , estradiol (E₂) , and IL-4 were detec- ted in the two groups using double antibody sandwich ELISA. Results Compared with before treatment, pruritus degree, scratching area, scaling, lichenoid lesion, irritability and restlessness, dysphoria, dry pharynx, dizziness, and tinnitus all decreased in the two groups after 8 weeks of treatment (P <0. 05). Scores of Chinese medical syndromes all decreased after 4 and 8 weeks of treatment (P <0. 05). Levels of SCF and DYN obviously decreased in the two groups after 4 and 8 weeks of treatment (P <0. 05,P < 0. 01). Compared with the control group, obvious improvement was seen in pruritus degree, scratching number, scaling, irritability and restlessness , dysphoria, dizziness , and tinnitus(P <0. 05) ; total scores of Chinese medical syndromes decreased (P <0. 05) ; SCF also decreased (P <0. 05) in the treatment group after 8 weeks of treatment. Conclusions Based on external application of Binghuang Fule Soft Ointment, GZR showed better efficacy than that of the control. It had certain roles in regulating related mediator levels that might affect nervous-endocrine-immune systems.

The present study aimed to evaluate the predictive value of pelvic anatomical and clinicopathological parameters for use in the estimation of the likely technical difficulties that may be encountered when performing open rectal surgery for mid-low rectal cancer. Sixty consecutive patients, undergoing open rectal surgery for mid-low rectal cancer were recruited between June 2009 and April 2014. All of the surgical procedures conducted, were low anterior resection (LAR) or abdominoperineal resection (APR). The operations were performed by the same surgeon and surgical team. Pelvic dimensions and angles were measured using three-dimensional reconstruction of spiral computerized tomography (CT) images. Operative time and intraoperative blood loss were used as indicators of operative difficulty. The independent variables were pelvic anatomical and clinicopathological parameters, and the dependent variables were operative time and intraoperative blood loss. Univariate and multivariate analyses were performed in order to determine the predictive significance of these variables. The pelvis width was significantly wider in females than in males (P<0.05), while the sacrococcygeal bending degree was significantly greater in males than in females (P<0.05). No significant difference were detected between the pelvis depth of females and males (P>0.05). Multivariate analyses showed that body mass index (BMI), tumor height, lymph node metastasis, anteroposterior diameter of the pelvic inlet, anteroposterior diameter of the pelvic outlet, height of the pubic symphysis, the sacrococcygeal distance, sacrococcygeal-pubic angle and diameter of the upper pubis to the coccyx were the main factors affecting the operative time (all P<0.05), while the maximum diameter of the tumor was the primary factor affecting intraoperative blood loss (P<0.05). Between the two procedures, the clinicopathological parameters appeared to be more valuable for predicting difficulty in LAR, in which operative time was associated with tumor height and tumor staging (R C 2 =0.312; P<0.001). By contrast, the pelvic anatomical parameters appeared to be more valuable predictors of variation in APR, in which intraoperative blood loss was associated with the anteroposterior diameter of the mid-pelvis, the anteroposterior diameter of the pelvic outlet, the interspinous diameter, the depth of the sacral curvature and the sacropubic distance (R C 2 =0.608; P=0.002). BMI, tumor height and the maximum diameter of the tumor may be used to predict the operative difficulty in performing open rectal surgery for mid-low rectal cancer. In addition to the associated clinicopathological parameters, wider, shallower and less curved pelvises may make the greatest contribution to reducing operative time and intraoperative blood loss. Operative difficulty is likely to be increased in deeper and narrower pelvises, or in those with greater sacrococcygeal curvature.

Purpose: This study aimed to develop a scoring system for evaluating the nail appearance after nail fusion plasty of the duplicated thumb, and to investigate the operation indication of the combination procedure and its effect on the postoperative nail appearance., Methods: The nail fusion plasty technique was carried out in 20 patients with congenital thumb duplication. The patients were followed up to observe the appearance of nail, and the results were assessed by our nail appearance evaluation criteria., Results: Twenty patients were followed up for 18 to 92 months (48 months on average). According to our criteria, we achieved excellent results in 12 cases, good in 6 cases, fair in 1 case, and poor in 1 case., Conclusions: The combination procedure is recommended when the size of the thumb is less than 80% of the size of the normal side or the width of the nail is less than 80% of that of the normal side. Satisfactory results can be obtained by careful operation. The newly devised scoring system assesses the nail appearance in a very comprehensive manner.

Osteosarcoma is one of the most common primary bone malignancies. Although there is a significant improvement of survival on osteosarcoma patients in the past decades, treatment of osteosarcoma is still unsatisfactory for the development of pulmonary metastasis. The potential prognostic value of p16(INK4a) in osteosarcoma has been investigated, however, the results from different studies were somewhat controversial. To elucidate whether p16(INK4a) is indeed a prognostic factor of osteosarcoma, we conducted a meta-analysis of the published literatures to provide a comprehensive evaluation of the significance of p16(INK4a) expression in patients with osteosarcoma. Eight studies with a total of 354 patients with osteosarcoma were examined. The pooled odds ratio (OR) with corresponding 95% confidence interval (95% CI) was calculated to evaluate the effect of p16(INK4a) expression on overall survival. Meta-analysis showed that patients with high p16(INK4a) expression were significantly associated with favourable overall survival when compared to their counterparts with low or undetectable p16(INK4a) expression (OR = 0.270, 95% CI 0.162-0.451, P < 0.001). Sensitivity analysis suggested the pooled OR was stable and not significantly changed when a single study was removed. In conclusion, the results from this meta-analysis highlight that p16(INK4a) is an effective biomarker of survival in patients with osteosarcoma.

Visfatin is identified a pro-inflammatory cytokine and its serum level is increased in various cancers. This study aimed to evaluate the prognostic value of preoperative serum visfatin level in breast cancers. Preoperative serum visfatin levels of 248 patients with breast cancer and serum visfatin levels of 100 healthy individuals and 100 benign women controls were determined using enzyme-linked immunosorbent assay. Unfavorable outcome was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause. Disease-free survival was defined as the time between surgery and the date of unfavorable outcome whichever appeared first. Overall survival was defined from surgery to death for any cause. The association of serum visfatin level with outcomes including mortality, unfavorable outcome, disease-free survival and overall survival was investigated by univariate and multivariate analyses. Preoperative serum visfatin level was substantially higher in patients than in healthy subjects and benign controls respectively. Elevated preoperative serum level of visfatin was identified an independent predictor of mortality, unfavorable outcome, disease-free survival and overall survival. Receiver operating characteristic curve analysis showed that serum level visfatin had high predictive value for mortality and unfavorable outcome. Thus, our results suggest that high preoperative serum visfatin level is associated with poor patient outcomes as well as may play a role as prognostic biomarker in breast cancer survival., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Stem/progenitor cells contribute to normal development of organs, but their mutation may lead to many human diseases including cancer. Stem/progenitor cells and some of the cancer cells have the same abilities of self-renewal and differentiation, suggesting that tumors were initiated from mutated stem/progenitor cells, the cancer stem/progenitor cells. The recent studies on the origin of the non-Hodgkin's lymphomas has proved that the second-hit aggravates gene mutation in lymphocytic progenitor cells, leading to the generation of lymphoma. This review summarizes the current advances in the studies of the second-hit at stem/progenitor cells in oncogenesis of B-cell non-Hodgkin's lymphoma.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, and some studies have suggested a beneficial effect on organ fibrosis, but their effects on dermal cell growth and extracellular matrix (ECM) turnover are unknown. To investigate the effect of the PPAR-gamma agonist troglitazone on cell growth and matrix production in human dermal fibroblasts (HDF), HDF were cultured and grown in a different concentration of troglitazone. PPAR-gamma expression and matrix production were measured in HDF in the presence of troglitazone. The mRNA expressions of TGF-beta1, collagen I (Col I) and fibronectin (FN) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein of transforming growth factor-beta1 (TGF-beta1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of Col I and FN were determined by Western blotting. The mRNA expression of TGF-beta1, Col I and FN were significantly decreased in HDF in 15-30 micromol l(-1) troglitazone compared to the control group with Dulbecco's modified Eagle's medium (P<0.01). An obvious decrease of TGF-beta1 protein was found in troglitazone-treated groups as compared to the control group (P<0.05). Exposure of HDF to troglitazone reduced col I secretion (P<0.05), and fibronectin secretion (P<0.05). This study suggests that PPAR-gamma agonist will provide a novel approach with therapeutic potential in dermal fibrosis, such as hypertrophic scar, keloid and so on., (Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.)

Through thorough analysis of the ecological security of lakes and reservoirs, which is the foundation of people' s living and regional sustainable development, the related mechanism between water system and social activities is elaborated. Then on the basis of pressure of human activities, the water quality and the service functions, the ecological security situations and trends of Dianchi Lake at time scale from 1999 to 2007 are analyzed. The results indicate that contamination gross control effectively relieves the pressure of human activities to some extent. But the water quality isn't obviously improved, and the grade of ecological security is not optimistic according to increasing index from 2005.

Objective: To provide basic information for epidemiological research of gastrointestinal (GI) malignant tumors., Methods: Data of GI cancer diagnosed in 15 hospitals of Heilongjiang province between January 1998 and December 2007 were analyzed retrospectively. The data mainly involved the age of onset, initial symptoms, pathological types, clinical staging and types of surgical procedure., Results: Gastric cancer was the most common type (45.8%) among the 33,540 GI cancer cases, then were rectal cancer (27.3%) and colon cancer (26.8%). Right colon cancer cases were more common than the left ones (1.3:1.0), particularly in people over 80 (2.1:1.0). Only 1.3% of colorectal cancer could be found in age under 30 years old. In patients aged 50 to 70, advanced gastric cancer accounted for 70.6%, advanced colon cancer 73.4% and advanced rectal cancer 72.4%. Well-moderately differentiated adenocarcinoma in early gastric cancer was 49.7%, early colon cancer 77.3% and rectal cancer 83.2%. Patients undergone radical excision in early gastric cancer accounted for 69.1%, advanced gastric cancer 79.9%, left colon cancer 91.9%, right colon cancer 83.9% and in rectal cancer for 88.3%., Conclusions: People aged 50 to 70 tend to get GI cancer in Heilongjiang province. Gastric cancer is the most common GI cancer. Radical excision is the main choice of therapy.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-gamma ligands in the presence of transforming growth factor-beta1 (TGF-beta1). In growth-arrested HSFs, a PPAR-gamma natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFbeta1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-gamma (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-beta1/Smad pathway. These results suggest that in TGFbeta1-stimulated HSFs, PPAR-gamma ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-gamma and Smad may be involved in the inhibitory effects of PPAR-gamma ligands.

Background: Pigs are currently considered the most likely source of organs for human xenotransplantation because of anatomical and physiological similarities to humans, and the relative ease to be bred in large numbers. Along with the fast development of the genetic engineering and organ transplant immunity medical science, the research of liver xenotransplantation suffers the very big valuing in recent years. Whether the livers from different species after transplanting can perform the normal function, depends on the function regeneration and lucid rates of hepatic portal vein. The objective of this study was to investigate the age effect on biomechanical properties of pig hepatic portal vein to pave the way for seeking a reliable biomaterial for future pig-to-human liver xenotransplantation., Methods: The biomechanical remodelling of the hepatic portal vein of pigs for 1,2,3,4,5 and 6 months (n = 6 per month) were measured in this study. The blood vessel was given periodic permanent loading and unloading, and repeated force-deformation data were obtained. The incremental modulus (Einc), the longitudinal incremental modulus (Ep), the circumferential incremental modulus (Ev), incremental compliance (C) and wall thickness were calculated based on the recorded pressure-diameter curves from experimental data., Results: The incremental modulus, pressure strain modulus and the volume modulus of the pig hepatic portal vein increases with the age increased (P < 0.01), while the compliance decreased with the increasing of the age (P < 0.01)., Conclusions: Our present study suggests that the biomechanical properties of the pig hepatic portal vein are age dependent, the pig hepatic portal vein with biomechanical properties that match those of human hepatic portal vein should be chosen for liver xenotransplantation.

Aim: To explore the clinicopathological and molecular genetic features of hereditary nonpolyposis colorectal cancer (HNPCC) in Chinese population., Methods: We collected 16 Chinese HNPCC families from Wenzhou, Zhejiang Province, China. Tumor tissues and peripheral white blood cells were studied using microdissection, microsatellite analysis, immunostaining of hMSH2 and hMLH1 proteins and direct DNA sequencing of hMSH2 and hMLH1 genes., Results: (1) A total of 50 patients had CRC. Average age at diagnosis of the first CRC was 45.7 years; 40.9% and 28.7% of the CRCs were located proximal to the splenic flexure and in the rectum, respectively. Thirty-eight percent of the colorectal cancer patients had synchronous and metachronous CRC. 34.4% and 25% of the CRCs were poor differentiation cancer and mucinous adenocarcinoma, respectively. Fourteen extracoloni tumors were found, and the hepatic cancer was the most common tumor type. Twenty-one patients whose median survival time was 5.7 years died during 1-23 years. Twenty-nine patients have survived for 1-28 years, 58.6%, 41.4% and 24.1% patients have survived for more than 5, 10 and 15 years, respectively; (2) All nine tumor-tissues showed microsatellite instability (MSI) at more than two loci. Four tumor-tissues lost hMSH2 protein expression and one lost hMLH1 protein expression. Three pathological germline mutations were identified from five genetically analyzed families; two of three mutations had not been reported previously as they were a transition from C to A in exon 14 (codon 743) of hMSH2 and a TTC deletion in exon 14 (codon 530) of hMLH1., Conclusion: Chinese HNPCC have specific clinicopathological features, such as early onset, propensity to involve the proximal colon, and high frequency of multiple CRCs, liver cancer more frequent than endometrial cancer. Chinese HNPCC showed relatively frequent germline mutation of mismatch repair (MMR) genes that correlated closely with high-level MSI and loss of expression of MMR genes protein.