[Penile cancer with perineural invasion is more prone to postoperative recurrence].

OBJECTIVE: To explore the correlation between perineural invasion and postoperative recurrence in patients surgically treated for penile cancer. METHODS: We conducted a retrospective analysis of the clinical data on 18 penile cancer patients surgically treated in our hospital from January 2018 to December 2021, 8 with postoperative recurrence (the recurrence group) and the other 10 without (the non-recurrence control group). We compared the two groups of patients in the age of onset, tumor-node-metastasis (TNM) stages, American Joint Committee on Cancer (AJCC) prognosis stages, surgical methods, perineural invasion and recurrence time. We analyzed the differences in postoperative recurrence using the Kaplan Meier plotted survival curve and in independent risk factors in predicting postoperative recurrence using the ROC curve. RESULTS: Compared with the non-recurrence controls, the patients in the recurrence group had a significantly older age of onset (P=0.0411) and severer perineural invasion (P<0.001), and those with perineural invasion had a shorter recurrence time (P<0.001), which was an independent risk factor for postoperative recurrence. The areas under the ROC curves for perineural invasion and age were 0.885 and 0.213, respectively. CONCLUSION: Penile cancer with perineural invasion is more prone to and perineural invasion is an independent risk factor for postoperative recurrence of the malignancy.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

Optimizing sparse sequencing of single cells for highly multiplex copy number profiling.

Genome-wide analysis at the level of single cells has recently emerged as a powerful tool to dissect genome heterogeneity in cancer, neurobiology, and development. To be truly transformative, single-cell approaches must affordably accommodate large numbers of single cells. This is feasible in the case of copy number variation (CNV), because CNV determination requires only sparse sequence coverage. We have used a combination of bioinformatic and molecular approaches to optimize single-cell DNA amplification and library preparation for highly multiplexed sequencing, yielding a method that can produce genome-wide CNV profiles of up to a hundred individual cells on a single lane of an Illumina HiSeq instrument. We apply the method to human cancer cell lines and biopsied cancer tissue, thereby illustrating its efficiency, reproducibility, and power to reveal underlying genetic heterogeneity and clonal phylogeny. The capacity of the method to facilitate the rapid profiling of hundreds to thousands of single-cell genomes represents a key step in making single-cell profiling an easily accessible tool for studying cell lineage.

[Effect of P and K Fertilization on Four Iridoids in Axial and Lateral Root of Gentiana crassicaulis].

Objective: To study the effect of phosphorus( P) and potassium( K) fertilization on four iridoids in axial and lateral root of Gentiana crassicaulis. Methods: Field experiment was conducted based on phosphorus and potassium,and the content of four iridoids was analyzed in the axial and lateral root of Gentiana crassicaulis. Results: Despite of different proportion of phosphorus and potassium,the content of four iridoids in axial root was always higher than that in the lateral root, and under normal fertilizer condition, the content of axial and lateral root was 12. 36% and 9. 84%, respectively. On the condition of phosphorus and potassium fertilization, the content of gentiopicroside and loganic acid were higher than that of the swertiamarin and sweroside both in the axial and lateral root. And the difference of the two parts could be increased by high potassium with appropriate phosphorus application. Conclusion: The four iridoids were more likely to accumulate in the axial root of Gentiana crassicaulis, and phosphorus and potassium fertilization, only affected the different degrees on the content of ingredients among two parts. Thus, more attention should be paid to the use of phosphorus and potassium fertilization, and the difference of the active ingredient content in the axial and lateral root of Gentiana crassicaulis.

The accuracy of computed tomography in the pretreatment staging of colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent cancers around the world. Multimodality therapies are used for CRC including surgery, chemotherapy, radiotherapy and targeted therapy. Correct treatment plan depends greatly on the accurate pretreatment staging. Computed tomography (CT) is a widely used detection and staging modality for CRC patients in clinical practice. The role of CT in assessing the patients with CRC has been well established, but the accuracy of pretreatment staging by CT varies in different reports. With the development of CT techniques, some reformations such as multi-detector CT (MDCT), CT with water enema or air insufflations, multiple planner reconstruction (MPR) help to give us higher resolution images in shorter time. The accuracy of CT for N staging was still not so ideal, but CT played an important role in chest and liver staging. Magnetic resonance imaging (MRI) and endorectal ultrasound (ERUS) may provide more precise images and evaluation of local T and N staging for rectal cancer. And positron emission tomography (PET) or PET/CT is recommended as a complement of CT, only for cases suspected of residual or recurrent colorectal carcinoma or before metastasectomy, not for routine use.

Biological features and quality comprehensive analysis of twelve germplasm resources of the genus Allium from Tibet.

Introduction: Allium is important vegetables and seasonings in China, Tibet is rich in unique resources of the genus Allium, but lacks development and utilization. Methods: We compared the biological features and comprehensively evaluating the quality of twelve germplasm resources of the genus Allium collected from Tibet. Results: The results revealed that nine germplasm resources were bolting and bloom normally except for SC015, SC019, and SC048, all twelve germplasm resources were able to vegetative growth. The individual differences in moisture, soluble sugar, and protein content among the twelve germplasm resources were relatively small, with pyruvic acid content ranging from 0.11 to 1.12 mg/g and a large variation coefficient. A total of 8 categories and 97 volatile compounds were detected in twelve germplasm resources, the majority possessed the highest proportions of aldehydes and organosulfur compounds, but there were certain differences between the different Allium species. Additionally, 11 to 16 types of free amino acids were present in all germplasm resources, proline exhibited the highest content. The total content of essential and non-essential amino acids in SC009 was the highest. Carbon (C) accounted for the largest proportion of all elements, and the contents of other mineral elements varied greatly among the different plants. Conclusion: In conclusion, combined with biological performance and comprehensive evaluation of quality, SC009 is the excellent germplasm resource suitable for growth and capable of reproduction with good quality. These results improved the exploitation and utilization of the genus Allium in Tibet, as well as provided germplasm resources for high-quality breeding of the genus Allium.

Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Reactive ballistic deposition of nanostructured model materials for electrochemical energy conversion and storage.

Porous, high surface area materials have critical roles in applications including catalysis, photochemistry, and energy storage. In these fields, researchers have demonstrated that the nanometer-scale structure modifies mechanical, optical, and electrical properties of the material, greatly influencing its behavior and performance. Such complex chemical systems can involve several distinct processes occurring in series or parallel. Understanding the influence of size and structure on the properties of these materials requires techniques for producing clean, simple model systems. In the fields of photoelectrochemistry and lithium storage, for example, researchers need to evaluate the effects of changing the electrode structure of a single material or producing electrodes of many different candidate materials while maintaining a distinctly favorable morphology. In this Account, we introduce our studies of the formation and characterization of high surface area, porous thin films synthesized by a process called reactive ballistic deposition (RBD). RBD is a simple method that provides control of the morphology, porosity, and surface area of thin films by manipulating the angle at which a metal-vapor flux impinges on the substrate during deposition. This approach is largely independent of the identity of the deposited material and relies upon limited surface diffusion during synthesis, which enables the formation of kinetically trapped structures. Here, we review our results for the deposition of films from a number of semiconductive materials that are important for applications such as photoelectrochemical water oxidation and lithium ion storage. The use of RBD has enabled us to systematically control individual aspects of both the structure and composition of thin film electrodes in order to probe the effects of each on the performance of the material. We have evaluated the performance of several materials for potential use in these applications and have identified processes that limit their performance. Use of model systems, such as these, for fundamental studies or materials screening processes likely will prove useful in developing new high-performance electrodes.

[A comparative study on the absorption kinetics parameters of rhubarb free anthraquinones between normal dogs and dogs with severe acute pancreatitis].

OBJECTIVE: To study the effects of severe acute pancreatitis (SAP) on absorption kinetic parameters of rhubarb free anthraquinones. METHODS: Eleven healthy Beagle dogs were randomly divided into the normal group (n = 6) and the SAP group (n = 5). The SAP animal model was prepared by surgery through portal vein blood channel building to collect blood from normal dogs and dogs with SAP. The free anthraquinones (20 mg/kg) was given by gastrogavage. The concentrations of five anthraquinones (aloe emodin, rhein, emodin, chrysophanol, and physcion) in the blood plasma of the portal vein and the femoral artery were determined using high performance liquid chromatography (HPLC). The kinetic parameters were calculated using MATLAB2007B Software. The half life (t(1/2Ka)), the absorption peak time (Tmax), the peak concentration (Cmax), the area under the curve [AUC(0-infinity)], and the mean residence time (MRT) were calculated using the statistical moment method. The transport velocity of corresponding medicines from the gastrointestinal tract to the blood (ka) was calculated. RESULTS: There was no difference in the chemical composition absorption type of the portal vein and the femoral artery between the two groups. Aloe emodin could be detected in the portal vein of each animal at each time point, and they were in the quantitative range. Rhein could be detected in the portal vein of each animal at each time point, and they were lower than the quantitative limit at few time points. Emodin and chrysophanol could be detected in the portal vein of partial animals at each time point, and most of them were higher than the quantitative limit. Physcion could be detected only in the portal vein of less animals at few time points. Rhein could be detected in the femoral artery at most time points, but the rhein plasma concentration at most time points were lower than the quantitative limit. Lower concentration of aloe emodin, emodin, and chrysophanol could be detected in the femoral artery at only few time points. Physcion was not detected in the femoral artery. The rhein plasma concentration of the femoral artery and the chrysophanol Cmax of the portal vein at 45 min were higher in the SAP group than in the normal group with statistical difference (P<0.05). There was no statistical difference in the rest indices. The AUC of rhein in the two groups were 59.32% and 66.07% of the total free anthraquinones respectively. CONCLUSIONS: SAP could not obviously affect the absorption kinetics parameters of rhubarb free anthraquinones. The intestinal tract and the liver might possibly play important roles in metabolizing or transforming rhubarb free anthraquinones.

Case Report: Rare Acute Abdomen: Focal Nodular Hyperplasia With Spontaneous Rupture.

Focal nodular hyperplasia (FNH) of the liver is a benign lesion characterized by hypertrophic nodules with central star-shaped fibrous scars. The etiology and pathogenesis of FNH are not completely understood. A 43-year-old man was hospitalized because of acute abdominal pain. Emergency computed tomography(CT) showed hepatic tumor rupture and bleeding. The patient's condition improved following arteriographic embolization to stop bleeding. Laparotomy confirmed spontaneous rupture and hemorrhage of focal hyperplasia and the patient remains asymptomatic after an uneventful recovery. FNH with spontaneous rupture and bleeding is extremely rare. Currently, there is no unified management standard for FNH and most previous studies recommend observation and follow-up. We recommend consideration of surgical treatment of cases with spontaneous rupture and bleeding.

Fast track multi-discipline treatment (FTMDT trial) versus conventional treatment in colorectal cancer--the design of a prospective randomized controlled study.

BACKGROUND: Laparoscopy-assisted surgery, fast-track perioperative treatment are both increasingly used in colorectal cancer treatment, for their short-time benefits of enhanced recovery and short hospital stays. However, the benefits of the integration of the Laparoscopy-assisted surgery, fast-track perioperative treatment, and even with the Xelox chemotherapy, are still unknown. In this study, the three treatments integration is defined as "Fast Track Multi-Discipline Treatment Model" for colorectal cancer and this model extends the benefits to the whole treatment process of colorectal cancer. The main purpose of the study is to explore the feasibility of "Fast Track Multi-Discipline Treatment" model in treatment of colorectal cancer. METHODS: The trial is a prospective randomized controlled study with 2 × 2 balanced factorial design. Patients eligible for the study will be randomized to 4 groups: (I) Laparoscopic surgery with fast track perioperative treatment and Xelox chemotherapy; (II) Open surgery with fast track perioperative treatment and Xelox chemotherapy; (III) Laparoscopic surgery with conventional perioperative treatment and mFolfox6 chemotherapy; (IV) Open surgery with conventional perioperative treatment and mFolfox6 chemotherapy. The primary endpoint of this study is the hospital stays. The secondary endpoints are the quality of life, chemotherapy related adverse events, surgical complications and hospitalization costs. Totally, 340 patients will be enrolled with 85 patients in each group. CONCLUSIONS: The study initiates a new treatment model "Fast Track Multi-Discipline Treatment" for colorectal cancer, and will provide feasibility evidence on the new model "Fast Track Multi-Discipline Treatment" for patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547.

A new SEIAR model on small-world networks to assess the intervention measures in the COVID-19 pandemics.

A new susceptible-exposed-infected-asymptomatically infected-removed (SEIAR) model is developed to depict the COVID-19 transmission process, considering the latent period and asymptomatically infected. We verify the suppression effect of typical measures, cultivating human awareness, and reducing social contacts. As for cutting off social connections, the feasible measures encompass social distancing policy, isolating infected communities, and isolating hub nodes. Furthermore, it is found that implementing corresponding anti-epidemic measures at different pandemic stages can achieve significant results at a low cost. In the beginning, global lockdown policy is necessary, but isolating infected wards and hub nodes could be more beneficial as the situation eases. The proposed SEIAR model emphasizes the latent period and asymptomatically infected, thus providing theoretical support for subsequent research.

γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury.

The mechanisms underlying sepsis-induced cardiomyopathy (SIC) remain poorly understood, and there are no specific therapeutics for SIC. We investigated the effects of maresin conjugates in tissue regeneration 1 (MCTR1) on SIC and explored its potential mechanisms. The experiments were conducted using an endotoxemia model induced by lipopolysaccharide (LPS). Mice were given MCTR1 intravenously 6 h after LPS stimulation. Echocardiography was performed to assess cardiac function 12 h after LPS administration. Treatment with MCTR1 significantly enhanced cardiac function and reduced LPS-induced increase of mRNA expression levels of inflammation cytokines. Transcriptomic analysis indicated that MCTR1 inhibited neutrophil chemotaxis via the IL-17 signaling pathway. We confirmed that MCTR1 reduced the expressions of neutrophil chemoattractants and neutrophil infiltration in the LPS-stimulated hearts. MCTR1 also resulted in a considerable reduction in IL-17A production mainly derived from γδ T cells. Moreover, our results provided the first evidence that neutralizing IL-17A or depletion of γδ T cells markedly decreased neutrophil recruitment and enhanced cardiac function in LPS-induced cardiac injury. These results suggest that MCTR1 alleviates neutrophil infiltration thereby improves cardiac function in LPS-induced cardiac injury via the IL-17 signaling pathway. Thus, MCTR1 represented a novel therapeutic strategy for patients with SIC.

Outcomes of a modified Bresler procedure for the treatment of rectocele with rectal intussusception.

BACKGROUND: Obstructed defecation syndrome (ODS) is a condition that is frequently caused by rectocele and rectal intussusception. This study aimed to evaluate the effectiveness of a modified Bresler procedure for the treatment of ODS. The outcomes of this modified procedure were compared with the stapled transanal rectal resection (STARR) procedure. METHODS: We performed a retrospective analysis of the clinical data from 76 female patients who presented with ODS between June 2014 and June 2016. The patients were divided into two treatment groups, namely Modified and STARR. Patients in the Modified group (n = 36) underwent the modified Bresler procedure, which involved posterior rectal-wall resection using a circular tubular stapler with multilevel purse-string sutures. Patients in the STARR group (n = 40) underwent the standard STARR procedure. We analysed post-operative complications, Wexner constipation scores (WCS), rectocele depths, and four-point post-operative satisfaction scales. RESULTS: Patients in the Modified group exhibited shorter operative times and fewer post-operative complications (both P < 0.05). At 12 months post-operatively, both the Modified and STARR groups displayed a significant improvement in the Wexner constipation score and the depth of rectocele. The post-operative WCS for the Modified group were significantly improved compared to those for the STARR group (P < 0.05), while there was no significant difference in the rectocele depth between the two groups (P > 0.05). Post-operative interviews at post-operative 12 months showed that patients in the Modified group had a better satisfaction (P = 0.05). CONCLUSIONS: Our modified procedure may be an effective treatment strategy for patients experiencing ODS caused by rectocele and rectal intussusception, with fewer complications and effective relief of symptoms.

[Investigation on current distribution of Oncomelania snails in schistosomiasis-endemic areas of Sichuan Province].

OBJECTIVE: To understand the current distribution of Oncomelania snails in Sichuan Province, so as to provide scientific evidence for formulating the schistosomiasis elimination strategy and implementing the precision schistosomiasis control measures in the province. METHODS: According to the National Scheme on Oncomelania hupensis Snails in China and the Scheme on Oncomelania hupensis Snails in Sichuan Province, snail surveys were performed in current snail habitats, historical snail habitats and suspected snail habitats using systematic sampling in Sichuan Province from 2016 to 2017, and the survey results were analyzed. RESULTS: From 2016 to 2017, a total of 88 346 settings were surveyed in schistosomiasis-endemic areas of Sichuan Province, and 19 314 settings were detected with snails, covering an area of 4 829.25 hm2, with no Schistosoma japonicum infection identified in snails. A total of 3 017 915 frames were investigated in Sichuan Province, and 1 041 417 frames were found to have living snails, with totally 1 791 115 living snails captured. The mean density of living snails was 0.59 snails/0.1 m2, and the mean percentage of frames with living snails was 34.51% in Sichuan Province. The current snail habitats were mainly distributed in 1 704 villages, 377 townships, 54 counties (districts) of 9 cities (prefectures) across the schistosomiasis-endemic areas of Sichuan Province. Snail habitats were mainly found in ditches (70.22%), and weeds were the predominant vegetation in snail habitats (66.45%). Snails were firstly discovered in Sichuan Province in 1913, and S. japonicum-infected snails were firstly identified in 1956, with the latest identification of S. japonicum-infected snails in 2008. CONCLUSIONS: There are many settings suitable for snail breeding in Sichuan Province, and snail monitoring and control should be intensified in the future.

[Surveillance of epidemic factors of schistosomiasis in wetlands in Sichuan Province].

OBJECTIVE: To investigate the epidemic factors of schistosomiasis in wetlands in Sichuan Province, so as to provide scientific evidence for the prevention and control of schistosomiasis in wetlands. METHODS: The artificial and natural wetlands were selected from Sichuan Province, and the relevant data regarding wetlands were collected. Routine snail survey, investigation on human morbidity due to schistosomiasis, snail diffusion experiments, questionnaire survey, determination of water infectivity and retrospective survey were conducted. RESULTS: In Sichuan Province, the mean densities of living snails were 0.003 snails/0.1 m2 and 2.033 snails/0.1 m2 in the upper and lower reaches of the Meiwan Reservoir wetlands, 0.08 snails/0.1 m2 in the Jinyan Lake of Guanghan City, 0.21 snails/0.1 m2 in Muhe River of Guanghan City, and 0.02 snails/0.1 m2 prior to the construction of Qiong-hai wetland park in Xichang City in 2015. Artificial simulation experiments showed that the largest distance of snail diffusion in water was 2 000 m. There were 8.80% (41/466) of subjects that lived neighboring wetlands, worked in wetlands and visited wet-lands having infested water contact behaviors. A total of 690 sentinel mice were assigned, and no Schistosoma japonicum infection was detected in the 677 mice dissected. Retrospective survey showed that the construction of the Meiwan Reservoir caused the spread of schistosomiasis in Dailing County, and snails were found in the ditches entering the Jinyan Lake and in Jinyan Lake areas 5 years following the construction of the Jinyan Lake in Guanghan City, with S. japonicum -infected snails detected in the ditches entering the Jinyan Lake. CONCLUSIONS: O. hupensis snails are found in some wetlands in Sichuan Province. Protection of wetlands and snail control with environmental improvements are recommended for the prevention of snail importation in natural wetlands, while in artificial wetlands, thorough snail control is recommended during the construction of the wetlands because of the likelihood of snail importation via water systems. In addition, both natural and artificial wetlands require long-term systematic surveillance of schistosomiasis.

[Comparison of clinical and genetic phenotypes between Chinese and Korean hereditary nonpolyposis colorectal cancer families].

OBJECTIVE: To compare the clinical and genetic features between Chinese and Korean hereditary nonpolyposis colorectal cancer (HNPCC) families. METHODS: Thirty-one Chinese HNPCC families and 63 HNPCC Korean families were involved in this study. The clinical data of the probands and families were collected. Genomic DNAs were prepared from peripheral blood samples of probands for DNA test. PCR and DHPLC were employed to screen the mutations. Sequencing analysis was followed to find out the exact mutation site and feature in samples showing abnormalities in SSCP or DHPLC analysis. RESULTS: In a total, there were 136 malignant neoplasms diagnosed in the 31 Chinese families, about 77.9% of them were colorectal cancer. The mean age of colorectal cancer at diagnosis was (48.6+/- 29.0) years. Gastric cancer was the second most common cancer in these familiesîSeven pathogenic mutations (3 in hMLH1 gene and 4 in hMSH2 gene) were detected in the 31 probands, including 2 missense mutations, 2 nonsense mutations, 2 frameshift mutations and 1 large-fragment deletion. The total mutation rate was 22.6%. In the 63 Korean families, 293 malignant neoplasms were documented, 82.6% of them were diagnosed as colorectal cancer. The mean age of colorectal cancer at diagnosis was (45.9+/- 11.0) years. Gastric cancer was also the most common extracolonic cancer in these Korean families. Nineteen pathogenic mutations (17 in hMLH1 gene and 2 in hMSH2 genes) were detected in the 63 probands, including 12 frameshift mutations, 5 missense mutations, 1 nonsense mutation and 1 base-change at the splicing site. The total mutation rate was 30.2%. CONCLUSION: (1) Chinese and Korean HNPCC families had many similar clinical features, such as early-onset of colorectal cancer, predominance in distal colon and rectum, lower incidence of synchronous or metachronous colorectal cancers as compared with Western countries, and a frequent occurrence of gastric cancer in the families. (2) The total mutation rate of hMLH1 and hMSH2 gene in Chinese and Korean HNPCC families was similar and lower than that reported in Western countries. But the mutation characteristics, such as predominant gene, mutation type and mutation distribution, were different in the two populations.

Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours.

Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy.

Analysis for phenotype of HNPCC in China.

AIM: The aims of this study were to identify the clinicopathological features of Chinese HNPCC families and to evaluate the value of criteria for suspected HNPCC (sHNPCC) in clinical diagnosis. METHODS: According to the follow-up records, 54 HNPCC families (including 12 ICG-HNPCC families and 42 sHNPCC families) were screened out from patients with colorectal cancers (CRCs), operated upon in 2(nd) Affiliated Hospital of Zhejiang University from 1984 to 2001. Clinical data of probands and tumor spectrum in these families were listed and analyzed. RESULTS: (1) Mean age, proportion of colonic cancer, poorly differentiated cancer, multiple CRCs and Dukes' A+B of the probands in ICG-HNPCC and sHNPCC kindred were 39ys and 47.5ys, 75 % and 62 %, 0 and 12.8 %, 16.7 % and 14.3 %, 58.3 % and 81 %,respectively. Compared with sporadic colorectal cancers, probands from ICG-HNPCC and sHNPCC families were obviously different at age of onset (P=0.025 and 0.031), tumor location (P=0.001 and 0.000), differentiation(P=0.002 and 0.011) and development of multiple tumors (P=0.014 and 0.002). (2) A total of 178 malignant neoplasms were found in 54 HNPCC families, including 139 colorectal cancers. Besides of colorectal cancer, extracolonic tumors occurred in stomach, endometrium, hepatobiliary system, and so on (8 gastric cancers, 6 endometrial cancers, 6 hepatobiliary system cancers and 19 others) can also be seen in Chinese ICG-HNPCC and sHNPCC families. CONCLUSION: (1) Chinese HNPCC families have specific clinicopathological features, such as early onset, predilection for the involvement of colon, tendency of multiple CRCs, development of extracolonic tumors and well differentiation. (2) The criteria for suspected HNPCC is useful in clinical diagnosis and management of HNPCC.

[Hypermethylation of hMLH1 promoter in sporadic colorectal cancer].

OBJECTIVE: To identify CpG island hypermethylation of 5'region of hMLH1 promotor and to explore its relationship to microsatellite instability(MSI)in sporadic colorectal carcinoma. METHODS: Forty-one pairs of tissue specimens (normal and cancer) were collected from 41 patients with colorectal cancer. Hypermethylation of hMLH1 promoter was detected by methylation specific PCR; the relationship between methylation and clinicopathological features was analyzed. Combined with BAT25 and BAT26, the MSI status was detected using an automated fluorescent DNA sequencer. RESULTS: Hypermethylation of hMLH1 promoter was detected in 75.6 % (31/41) of samples. Mean age of unmethylation cases (49.2 y) was significantly younger than that of methylation cases (63.6 y) (P<0.05), but there were no differences between two groups in other clinicopathological features. MSI was detected in 43.9 % samples (18/41); hypermethylation of hMLH1 promoter was detected in 94.4 % (17/18) of MSI(+) samples, which was higher than that in MSI(-) samples (60.9 %,14/23, P<0.05). CONCLUSION: Age-related hypermethylation is generally found in patients with sporadic colorectal cancers, which may cause MSI and might be the mechanism in the development of colorectal cancer of elderly people.