[Application of preoperative serum CYFRA 21-1 level in the prognosis of colorectal cancer].

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.

Analysis of the relationship between ribosomal DNA ITS sequences and active components in Rhodiola plants.

Rhodiola plants are a valuable resource in traditional Chinese medicine. The objective of this study was to evaluate the correlation between ribosomal DNA internal transcribed spacer (ITS) sequences and the three active components in Rhodiola plants. For this, we determined ITS sequence polymorphisms and the concentrations of active components salidroside, tyrosol, and gallic acid in different Rhodiola species from the Tibetan Plateau. In a total of 23 Rhodiola samples, 16 different haplotypes were defined based on their ITS sequences. Analysis of the active components in these same samples revealed that salidroside was not detected in species with haplotypes H4, H5, or H10, tyrosol was not detected with haplotypes H3, H5, H7, H10, H14, or H15, and gallic acid was detected in with all haplotypes except H14 and H15. In addition, the concentrations of salidroside, tyrosol and gallic acid varied between samples with different haplotypes as well as those with the same haplotype, implying that no significant correlation exists between haplotype and salidroside, tyrosol or gallic acid concentrations. However, a statistically significant positive correlation was observed for among these three active components.

Influence of colorectal cancer tumor suppressor gene CHD5 methylation on its clinical and pathological characteristics.

Recently, abnormal tumor suppressor gene (TSG) methylation has become a hotspot in the research on colorectal cancer (CRC). This study aimed to explore the influence of CHD5 methylation of CRC TSG on its clinical and pathological characteristics. A total of 40 operation samples as well as corresponding tissue specimens were collected from CRC patients treated in the First Affiliated Hospital of Zhengzhou University from January to December in 2014. CHD5 gene methylation in tissue specimens was detected with methylation specific polymerase chain reaction (MSP); moreover, messenger ribose nucleic acid (mRNA) expression of CHD5 in each tissue was tested using reverse transcription-polymerase chain reaction (RT-PCR), and Western blot was applied to detect the expression of CHD5 protein in those tissues and to analyze the correlation between mRNA and protein of cancer tissue CHD5 as well as the relationship between CHD5 methylation and protein expression. Results revealed that the expression rate of CHD5 methylation in 40 normal mucosal tissues, para-carcinoma tissues, adenoma tissues and CRC tissues was 12.5% (5/40), 22.5% (9/40), 47.5% (19/40) and 72.5% (33/40), respectively. The mRNA expression of CHD5 in the above tissues was 0.225±0.276, 0.169±0.231, 0.147±0.159 and 0.013±0.011 and the protein expression of CHD5 was 0.438±0.205, 0.398±0.180, 0.156±0.1 and 0.024±0.311, respectively. Methylation rate of CHD5 was 87% (20/23) in 23 cases of CHD5 protein loss expression and 52.9% (9/17) in 17 cases of CHD5 protein expression. Results of chi-squared test indicated that there was a significant difference in methylation rate (P less than 0.05), that is, the methylation rate of negatively expressed CHD5 protein was obviously higher than positively expressed protein. Thus, it can be concluded that the CHD5 methylation rate rises gradually in the evolution of CRC, which is related to the occurrence and development of CRC. Furthermore, CHD5 mRNA is positively correlated with protein expression and CHD5 gene methylation is associated with protein loss expression. Therefore, TSG CHD5 methylation of rectal cancer has a great effect in influencing its clinical and pathological features.

Vitamin D receptor genetic variants are associated with susceptibility of gallbladder adenocarcinoma in a Chinese cohort.

The aim of this study was to test for the possible association between vitamin D receptor (VDR) genetic variants and susceptibility to gallbladder cancer (GBC). A total of 291 GBC cases were recruited and 396 gender- and age-matched healthy volunteers were enrolled as controls. The VDR gene polymorphisms were determined in all subjects. The genotype and the allele frequencies of ApaI, BsmI, and TaqI polymorphisms were not significantly different between GBC subjects and controls. However, the genotype and allele frequencies of the FokI C>T polymorphism were significantly different between GBC subjects and controls. The FokI TT genotype was in markedly higher frequency in GBC subjects compared to controls (38.14 vs 22.73%, P < 0.001). Using TT as the reference genotype, multivariate logistic regression analysis showed that CC genotype carriers had a higher risk of GBC (adjusted odds ratio (OR) = 3.423, adjusted P = 0.001) with adjustment for age, gender, smoking status, alcohol use, and gallstone presence, as well as the serum 1,25(OH)2D level. Carriers of the CT genotype also had a higher risk of GBC (adjusted OR = 1.992, adjusted P = 0.003). Multivariate logistic regression analysis did not reveal any association between the ApaI, BsmI, and TaqI polymorphisms and GBC risk (all P > 0.05).

[Progress of laparoscopy and endoscopy cooperative surgery for early colorectal tumors].

Cooperative laparoscopic or robotic-endoscopic surgery has emerged as a promising approach for the treatment of early-stage colorectal cancers that are difficult to treat with endoscopic techniques alone. Cooperative surgery allows organ and function preservation by complementing the advantages of each modality, providing minimally invasive, precise and personalized treatment options. Laparoscopic-endoscopic cooperative surgery includes laparoscopic-assisted endoscopic resection, combined laparoscopic-endoscopic full-thickness resection, endoscopic-assisted laparoscopic wedge resection, endoscopic-assisted laparoscopic segmental resection, and laparoscopic-endoscopic cooperative surgery with sentinel lymph node dissection. Nearly three decades of clinical research and practice have demonstrated the safety and efficacy of laparoscopic and endoscopic cooperative surgery in the treatment of colorectal tumors. With the progress of the minimally invasive concept, the development of minimally invasive technology and the innovation of minimally invasive equipment, laparoscopy and endoscopy cooperative surgery is expected to have a proper place in the treatment of colorectal tumors.

[Perioperative management and operative treatment of malignant tumor of anal canal merging severe abdominal protuberance].

Objective: To report the perioperative management and robot-assisted minimally invasive surgery results of one case with malignant tumor of anal canal combined with severe abdominal distention. Methods: A 66-year-old male suffer from adenocarcinoma of anal canal (T3N0M0) with megacolon, megabladder and scoliosis. The extreme distention of the colon and bladder result in severe abdominal distention. The left diaphragm moved up markedly and the heart was moved to the right side of the thoracic cavity. Moreover, there was also anal stenosis with incomplete intestinal obstruction. Preoperative preparation: fluid diet, intravenous nutrition and repeated enema to void feces and gas in the large intestine 1 week before operation. Foley catheter was placed three days before surgery and irrigated with saline. After relief of abdominal distention, robotic-assisted abdominoperineal resection+ subtotal colectomy+colostomy was performed. Results: Water intake within 6 hours post-operatively; ambulance on Day 1; anal passage of gas on Day 2; semi-fluid diet on Day 3; safely discharged on Day 6. Conclusion: Robotic-assisted minimally invasive surgery is safe and feasible for patients with malignant tumor of anal canal combined with severe abdominal distention after appropriate and effective preoperative preparation to relieve abdominal distention.

[Application of robotic (or laparoscopic) surgery combined with colonoscopy in T1 stage colorectal cancer surgery: 13 cases].

Objective: To investigate the feasibility and safety of a robotic surgical system (or laparoscopy) in combination with colonoscopy (combined) for the treatment of stage T1N0M0 colorectal cancer. Methods: This was a descriptive case series. Indications for combined dual-scope surgery in this study were as follows: (1) preoperative colonoscopic examination of lesions in the middle and upper rectum and colon with pathologically confirmed high-grade intraepithelial neoplasia, intramucosal adenocarcinoma, or adenocarcinoma; (2) no distant or local lymph node metastases; and (3) endoscopic ultrasound and magnetic resonance imaging evidence of tumor invasion of the mucosal or submucosal, but not the muscular, layer (i.e., T1). The clinical data of 13 patients with stage T1 colorectal cancer who had undergone dual-scope combined resection using a robotic surgery system or laparoscope-assisted combined colonoscopy surgery at the First Affiliated Hospital of Zhengzhou University from April to October 2022 were retrospectively collected, including 6 males and 7 females, with a median age of 59 (48~88) years old. The tumors were located in the upper and middle rectum in six patients, in the sigmoid colon in three, and in the ascending colon in four. The median maximum diameter of the tumors was 3.0 (1.8-5.0) cm. The surgery was performed by a robotic surgery system (or laparoscopy) with peritumoral D1 lymph node dissection at the first station in the tumor area. The tumors were resected under direct vision and the defects in the intestinal wall were using a robotic surgery system (or laparoscopy). A robotic surgery system was combined with colonoscopy in eight cases and laparoscopy combined with colonoscopy in the remaining five. Studied variables includes surgical and pathological features, postoperative factors, and outcomes. Results: Surgery was successful in all 13 patients with no need for conversion to open surgery or intraoperative blood transfusion. The median operating time was 85 (60-120) minutes, median intraoperative bleeding 3 (2-5) mL, median number of lymph nodes harvested 3 (1-5), and the median circumferential resection margin 0.8 (0.5-1.0) cm. Postoperative pathological examination showed lymph node metastasis in one patient, who therefore underwent additional radical surgery. The median postoperative time to ambulation was 1 (1-2) days. The urinary catheters of all patients were removed 1 day after surgery and the median length of stay was 4 (3-5) days. No abdominal infection, anastomotic leakage or bleeding occurred in any of the study patients. The median follow-up time was 10 (6-12) months, during which no tumor recurrence or metastasis was found, and the quality of life was satisfactory. Conclusions: The combination of two minimally invasive platforms, a robotic surgery system (or laparoscopy) and colonoscopy, is safe and feasible for resection of stage T1 colorectal cancer and has a good short-term prognosis.

[Progress in intestinal adaptation after enterectomy].

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.

[Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder].

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.

[Comparison of clinical efficacy of robotic, laparoscopic and open surgery in the treatment of severe rectal prolapse].

Objective: To analyze and compare the efficacy of robotic, laparoscopic and open dorsal mesh rectopexy in the treatment of severe rectal prolapse. Methods: A retrospective cohort study was performed. Patients who had a full-thickness rectum pulled out of the anus before surgery and the length was greater than 8 cm, and underwent transabdominal dorsal mesh rectopexy were enrolled in the study. Those who had urinary or sexual dysfunction before surgery, could not perform sexual function scores due to lack of a fixed sexual partner or sexual activity after surgery, underwent laparotomy again during the perioperative period, were transferred to laparotomy during robotic or laparoscopic surgery, or had no complete information, were excluded. A total of 61 patients with severe rectal prolapse in the First Affiliated Hospital of Zhengzhou University from 2014 to 2018 were enrolled and divided into robotic group (20 cases), laparoscopic group (20 cases) and open group (21 cases) according to the operative procedure based on patients' will. Perioperative parameters were compared among the 3 groups. The International Prostatic Symptoms Score Scale (IPSS, higher score indicates more severe urinary dysfunction), the International Index of Erectile Function questionnaire (IIEF-15, lower score indicates more severe male sexual dysfunction) and the Female Sexual Function Index (FSFI-19, lower score indicates more severe female sexual dysfunction) were used to evaluate and compare the urinary and sexual function before and after operation. Results: There were no significant differences in baseline data among the 3 groups (all P>0.05). In the robotic, laparoscopic and open groups respectively, the operative time was (176.3±13.8) minutes, (160.2±12.1) minutes and (134.2±12.1) minutes; intraoperative blood loss was (58.5±18.9) ml, (67.9±15.7) ml and (114.2±8.4) ml; the first time to ambulation was (19.9±6.8) hours, (24.0±8.9) hours and (37.7±11.4) hours; the first time to gas passage was (31.8±6.8) hours, (35.7±8.9) hours and (49.2±11.2) hours; the hospitalization time was (11.0±1.4) days, (11.4±1.4) days and (13.3±2.1) days; whose differences among 3 groups were all significant (all P<0.001). While no significant differences in morbidity of complication and recurrence among 3 groups were observed (all P>0.05). In the robotic, laparoscopic and open groups respectively, the preoperative IPSS score was (4.2±1.7), (4.4±1.3), and (4.7±1.8); the IPSS score at postoperative 3-month was (8.5±2.5), (9.9±1.7), and (12.2±3.1); IPSS score at postoperative 12-month was (4.3±1.6), (5.8±1.3), and (6.3±1.5), respectively. Compared to preoperative score, postoperative IPSS score increased obviously, then decreased gradually (P<0.001). Preoperative male IIEE score was (22.8±1.8), (22.1±2.1), and (22.6±1.5). In the robotic, laparoscopic and open groups respectively, male IIEE score at postoperative 6-month was (19.6±2.1), (17.1±2.1), and (15.0±2.1); male IIEE score at postoperative 12-month was (22.4±1.6), (19.9±1.5), (17.9±1.8), respectively. Preoperative female FSFI score was (26.4±3.4), (26.6±3.2), and (26.6±3.0); female FSFI score at postoperative 6-month was (21.5±3.3), (18.9±2.9), (17.0±2.6); female FSFI score at postoperative 12-month was (26.1±2.7), (22.7±3.2), and (21.2±2.3), respectively. Postoperative male IIEE score and female FSFI score decreased significantly and then increased gradually with time, whose differences were all significant (all P<0.05). Postoperative IPSS, IIEE, and FSFI scores in the robotic group were superior to those in the laparoscopic and open groups (all P<0.05). Conclusion: Robotic surgery is safe and effective in the treatment of severe rectal prolapse, and is more advantageous in preserving urinary function and sexual function.

Targeting colon cancer stem cells with novel blood cholesterol drug pitavastatin.

OBJECTIVE: Previous studies have demonstrated the importance of stem cells in human cancer, including colon cancer. Pitavastatin is approved for the treatment of hyperlipidemia and has also been shown to inhibit stem cell proliferation in preliminary in vitro studies. This study was done to investigate the effects of pitavastatin on human colon carcinoma stem cells (coCSCs) in vitro and in mouse tumor xenografts in vivo. MATERIALS AND METHODS: Human colon adenocarcinoma cell lines, SW480 and SW620, were cultured to the spheroid formation. The effects of pitavastatin on colon cancer stem cells were studied using the colorimetric MTT cell proliferation assay; quantitative polymerase chain reaction was used to determine the expression of cell cycle genes, OCT4, SOX2, and NANOG; Western blots were performed to measure MDR1. Mice were injected subcutaneously with SW480 cells; the growth of these tumor xenografts was studied using volumetric analysis following pitavastatin treatment. RESULTS: Specific cell culture medium provided conditions that resulted in the expression of colon cancer stem cell markers when compared with normal cultured cells. Colon cancer stem cells were inhibited by pitavastatin treatment. Pitavastatin reduced the expression of stem cell markers of colon cancer stem cells and induced the cell apoptosis. Pitavastatin inhibited the growth of mouse tumor xenografts. CONCLUSIONS: The findings of this preliminary study have demonstrated a potential role for pitavastatin in the inhibition of stem cell proliferation in colon carcinoma. Further studies are recommended to determine the mechanism of these effects on colon carcinoma cells in vitro and in vivo.

An autosomal genomic scan for loci linked to type 2 diabetes in northern Han Chinese.

We report the results of a genome-wide scan conducted in 219 individuals from 34 large multiplex nuclear pedigrees from the northern Han Chinese population at an average resolution of about 10 cM. Nonparametric two-point and multipoint linkage analyses were performed to detect evidence of linkage with type 2 diabetes in this study. On chromosome 1 four regions showed evidence of linkage with type 2 diabetes in northern Han Chinese. Of these regions a marker D1S193 (73 cM) showed evidence of linkage (two-point nonparametric linkage 2.409), and another region (around 190 cM) was a replication of several other studies performed in different ethnic populations. Evidences of linkage have been confirmed by typing additional markers (average distance 1-5 cM) flanking these two positive regions on chromosome 1. We also found indication of linkage with type 2 diabetes on chromosomes 2, 10, 12, 18, 20, and 22 by two-point linkage analyses.

Linkage of hypertension to chromosome 2q14-q23 in Chinese families.

OBJECTIVES: To identify chromosome regions containing hypertension susceptibility genes in Chinese. SUBJECTS AND METHODS: A three-stage study was carried out in Chinese siblings ascertained through outpatient clinics. In the first stage, 283 affected sib-pairs from 79 nuclear families were subjected to a genome-wide scan with 240 microsatellite marker loci. The second stage focused on chromosome 2 with additional markers resulting in an average distance of 5 cM and used an independent sample of 637 affected sib-pairs from 161 families. In the third stage, a fine-scale mapping study on the suggestive region was performed in an independent set of 777 affected sib-pairs from 106 families. Fourteen markers were used with an average distance less than 2 cM. Non-parametric linkage analyses (NPL), parametric linkage analyses and transmission-disequilibrium tests were used to assess evidence for linkage and association. RESULTS: Three markers (D2S168 at 27.06 cM, D2S151 at 152.04 cM and D2S142 at 161.26 cM) on chromosome 2 with suggestive linkage to hypertension susceptibility genes were identified in the genome-wide scan. In stage II, the suggestive region around D2S151 and D2S142 was replicated, while the linkage around D2S168 was not. In the stage III fine-scale mapping study, multipoint linkage analyses showed LOD scores greater than 2.0 throughout a region between 157.16 cM and 162.46 cM (all P < 0.001) with a maximum peak of 2.24 (P= 0.00067) at 160.52 cM. We also observed a NPL Z-score peak of 3.27 at 157.55 cM (P= 0.00086). CONCLUSIONS: The results of a suggestive region on chromosome 2q14-q23 (D2S112-D2S2370) were consistent between each of the three studies. Interestingly, this region overlaps a syntenic region that contains blood pressure quantitative trait loci identified in rat models of hypertension. These data suggest that the region near D2S142 and D2S151 deserves to be further screened for hypertension susceptibility genes.

A mutation in SART3 gene in a Chinese pedigree with disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic disorder of keratinization, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, and the genetic basis and pathogenesis of this disorder have not been elucidated. OBJECTIVES: To determine the locus of DSAP and identify the candidate gene(s) of the disease. METHODS: Genome-wide scan and linkage analysis were performed in a six-generation Chinese family with DSAP. The coding exons of the candidate genes were sequenced to analyse and detect the nucleotide variations. RESULTS: Linkage analysis showed that the maximum two-point lod score of 5.56 was obtained with the marker D12S79 at a recombination fraction theta of 0.00. Haplotype analysis defined the critical region for DSAP between D12S330 and D12S1612 on 12q24.1-24.2. By sequence analysis, we found a Val591Met mutation in SART3 in all affected individuals of the family. CONCLUSION: SART3 is a candidate gene for DSAP, and is possibly involved in the pathogenesis of DSAP.

A genome-wide search for type II diabetes susceptibility genes in Chinese Hans.

AIMS/HYPOTHESIS: The aim of the study was to search for Type II (non-insulin-dependent) diabetes mellitus susceptibility genes in a Chinese population. METHODS: A genome-wide scan was carried out using non-parametric linkage analyses. We studied 102 families (478 family members) who were Chinese Hans residing in east and south-east China, including 282 diabetic patients, among them 142 independent affected sibpairs were available for genotyping. A total of 247 fluorescence labelled microsatellite markers, with an average resolution of 15 cM, were amplified. GENEHUNTER was used for the non-parametric linkage analyses. RESULTS: Two loci on chromosome 9 D9S171 and D9S175 showed suggestive evidence for linkage, with an NPL-score of 3.286 and 2.939 respectively, and a p value of 1.19 x 10(-4) and 4.47 x 10(-4). A locus on the long arm of chromosome 20, D20S196 showed a rise in the non-parametric-linkage score (from 1.517 to 2.922) and a corresponding decrease in the p value from 0.04 to 6.5 x 10(-4) when families with lower BMI were analysed alone. Other loci with weaker evidence for linkage were also observed. CONCLUSIONS: Our results suggest that chromosome 9 contains genes involved in the susceptibility to Type II diabetes in an eastern and southeastern Chinese Han population, and chromosome 20 could hide genes linked to Type II diabetes in families with a lower BMI. Other regions could also hide susceptibility genes with minor effects.

Refined localization of dyschromatosis symmetrica hereditaria gene to a 9.4-cM region at 1q21-22 and a literature review of 136 cases reported in China.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis characterized by hyperpigmented and hypopigmented macules on the extremities, which has recently been mapped to an 11.6-cM interval on chromosome 1q11-21. So far, most cases of DSH have been reported in Japan and dermatologists around the world might think this disorder mainly occurs in Japan. In fact, there are 17 DSH families including 136 cases reported in China since 1980, but most of them are described in Chinese. OBJECTIVES: To refine the previously mapped region that facilitates the identification of the DSH gene and to delineate the clinical and genetic features of Chinese DSH cases by a literature review of 136 cases reported in China. METHODS: We performed genotyping and linkage analysis using polymorphic microsatellite markers at 1q11-22 in two Chinese DSH families, and reviewed all of the DSH cases reported in China since 1980. RESULTS: A cumulative maximum two-point lod score of 3.68 was produced with marker D1S506 at a recombination frequency of theta = 0.00 in these two families. Haplotype analysis refined the DSH locus to a 9.4-cM interval flanked by D1S2343 and D1S2635. The genetic and clinical features of Chinese cases with DSH were summarized. In some Chinese cases, hyperpigmented and hypopigmented macules were scattered on the neck and chest, but among Japanese patients there were no similar skin lesions to be reported on these sites. CONCLUSIONS: This study confirms linkage of DSH to a previously mapped region and refines the DSH gene to a 9.4-cM interval at 1q21-22. Likewise, the literature review indicates that DSH is not an uncommon disorder in China and the differences in the distribution of skin lesions could be related to race and environment.