[Effects of preoperative diagnostic hysteroscopy on peritoneal cytology and prognosis in patients with non-endometrioid carcinoma].

Objective: To explore the effects of preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage on the risk of abdominal dissemination and prognosis of non-endometrioid carcinoma. Methods: The clinical and pathological data of 97 patients who underwent surgical treatment and were pathologically confirmed as non-endometrioid carcinoma (including serous carcinoma, clear cell carcinoma, mixed adenocarcinoma, and undifferentiated carcinoma, etc.) from October 2008 to December 2021 in Peking University People's Hospital, were collected for retrospective analysis. According to preoperative diagnostic methods, they were divided into hysteroscopic group (n=44) and non-hysteroscopic group (n=53). The impact of hysteroscopy examination on peritoneal cytology and prognosis was analyzed. Results: (1) There were no statistical differences in age, body mass index, tumor size, pathological characteristics, and treatment methods between the hysteroscopic group and the non-hysteroscopic group (all P>0.05), but the proportion of stage Ⅰ-Ⅱ patients in the hysteroscopic group was significantly higher than that in the non-hysteroscopic group [68% (30/44) vs 47% (25/53); χ2=4.32, P=0.038]. (2) Among 97 patients, 25 (26%, 25/97) of them were cytologically positive for ascites. The hysteroscopic group had a lower positive rate of peritoneal cytology than that in the non-hysteroscopy group, which was significantly different [11% (5/44) vs 38% (20/53); χ2=8.74, P=0.003]. Stratification according to surgical and pathological stages showed that the positive rate of peritoneal cytology in the hysteroscopic group (3%, 1/30) was lower than that in the non-hysteroscopic group (12%, 3/25) in the 55 patients with stage Ⅰ-Ⅱ, and that in the hysteroscopic group (4/14) was also lower than that in the non-hysteroscopic group (61%, 17/28) in the 42 patients with stage Ⅲ-Ⅳ. There were no significant differences (all P>0.05). (3) The 5-year disease-free survival (DFS) rate of the hysteroscopic group and the non-hysteroscopic group were respectively 72.7% and 60.4%, and there was no significant difference between the two groups (P=0.186). After stratification according to staging, the 5-year DFS rate were respectively 90.0% and 72.0% (P=0.051) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅰ-Ⅱ, and 35.7% and 50.0% (P=0.218) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅲ-Ⅳ, in which there were not statistically significant differences. The 5-year overall survival (OS) rate were respectively 86.4% and 81.1% between the hysteroscopic group and the non-hysteroscopic group, with no significant difference between the two groups (P=0.388). The 5-year OS rate were respectively 93.3% and 96.0% in the hysteroscopic group and non-hysteroscopic group for patients with stage Ⅰ-Ⅱ(P=0.872), and 71.4% and 67.9% in the hysteroscopic group and non-hysteroscopic group in patients with stage Ⅲ-Ⅳ (P=0.999), with no statistical significance. Conclusions: Diagnostic hysteroscopy do not increase the rate of positive peritoneal cytology result at the time of surgery in this cohort, and no significant correlation between preoperative hysteroscopy examination and poor prognosis of non-endometrioid carcinoma is observed. Therefore, preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage in non-endometrioid carcinoma maybe safe.

[Prognosis analysis of radical or modified radical hysterectomy and simple hysterectomy in patients with stage â ¡ endometrial cancer].

Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.

[Application and prospect of PD-1 or PD-L1 inhibitor in advanced hepatocellular carcinoma].

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors of the digestive system in the clinic. In recent years, the proposal and development of immunotherapy have set off a worldwide anticancer upsurge. In particular, programmed death receptor 1(PD-1) and programmed death receptor ligand 1(PD-L1) inhibitor have been used in a wide variety of tumor diseases and achieved good curative effect. However, the application of PD-1 or PD-L1 inhibitors in HCC is mostly still at the stage of clinical trials, and some clinical trials have shown gratifying results in patients with advanced HCC and postoperative recurrence. More studies have shown that PD-1 or PD-L1 inhibitors combined with radiofrequency, chemoradiotherapy, and molecular targeted drugs can bring greater benefits to patients.

[Cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation].

To compare the clinical features and prognosis in patients with cytomegalovirus pneumonia from other pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 118 patients with pulmonary complications after allo-HSCT from March 2016 to June 2019 were analyzed retrospectively, who were divided into cytomegalovirus (CMV) pneumonia group (n=34) and the non-CMV pneumonia group (n=84). Compared with non-CMV pneumonia group, CMV pneumonia group presented earlier median onset time (1.8 vs.6.0 months, P=0.015) after allo-HSCT, more dyspnea (41.2% vs. 19.0%, P=0.012), hypoxemia (38.2% vs. 13.1%, P=0.006), and interstitial pneumonia (82.4% vs. 23.8%,P<0.01).The incidence of CMV-viremia and serum viral load in CMV pneumonia group were significantly higher than those in non-CMV pneumonia group. Consistently, and the development of mixed infection in CMV pneumonia group was higher than that of non-CMV pneumonia group (41.2% vs. 16.7%, P=0.013). The median follow-up time was 12.8 (0.4-46.5) months. The 1-year attributable mortality in CMV pneumonia group was significantly higher than that in non-CMV pneumonia group (26.5% vs. 10.7%, P=0.004), while the 1-year overall survival rate was significantly lower than that in non-CMV pneumonia group (61.8% vs. 85.7%, P=0.001). Reduced-intensity conditioning (RIC)(P=0.036), high flow ventilation (P=0.033) and negative CMV-viremia (P=0.009) were unfavorable prognostic factors of patients with CMV pneumonia. Compared with those with non-CMV pneumonia, patients with CMV pneumonia had more characteristic clinical manifestations and imaging features. However, due to the higher incidence of mixed infections, the causes of pneumonia need to be identified by bronchoscopic alveolar lavage. In conclusion, patients with CMV pneumonia have worse clinical outcome. RIC, high flow ventilation and negative CMV-viremia are adverse prognostic factors for CMV pneumonia.

[Clinical study of 34 patients with cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the clinical features and prognosis of cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: We reviewed the clinical features and laboratory data of cytomegalovirus pneumonia patients after allogeneic peripheral blood HSCT from March 1, 2016 to June 30, 2019 at the hematology department of the Shanghai general hospital and analyze the prognostic factors. Results: Of the 411 allo-HSCT patients, 34(8.3%)developed CMV pneumonia after transplantation, including 18 men and 16 women, with a median age of 32(8-62)y. Total 14 patients had acute myeloid leukemia, 10 had acute lymphoblastic leukemia, 5 had myelodysplastic syndrome, 3 had non-Hodgkin's lymphoma, and 2 had aplastic anemia. The median onset time for CMV pneumonia was 53(36-506)d after transplantation. The main symptoms were cough(26 cases, 76.5%), fever(23 cases, 67.6%), and shortness of breath(14 cases, 41.2%). Only 17.6%(6/34)patients had expectoration, and 2 cases(5.9%)had no obvious symptoms in the early stage, but were diagnosed on routine chest CT examination. Twenty-eight(82.4%)patients showed signs of typical interstitial pneumonia, such as lobular central nodule and diffuse ground glass opacity; 6(17.6%)patients showed atypical imaging changes of patch, nodule, and consolidation. Further, 26 patients(76.5%)were positive for CMV-DNA, and the copy number was lower than that of BALF[1.70×10(7)(5.44×10(5)-4.45×10(9))copies/L vs 1.45×10(8)(1.10×10(7)-1.10×10(11))copies/L, P=0.004]. Thirteen(38.24%)patients with CMV pneumonia had mixed infection with other lower respiratory tract pathogens(10 strains of fungi, 6 strains of bacteria, and 1 of adenoviruses). The median follow-up duration was 12.8(0.4-46.5)months. The OS rate was 58.82%. Age ≥ 40 y and high flow ventilation were independent risk factors for poor prognosis in CMV pneumonia patients(P=0.049, P=0.009). Conclusion: Bronchoscopic bronchoalveolar lavage fluid detection helps in improving the accuracy of the etiological diagnosis of CMV pneumonia after allo-HSCT. Age ≥ 40 y and high flow ventilation were independent risk factors for poor prognosis in patients with CMV pneumonia.

[Analysis of EGFR mutation and clinical features of lung cancer in Yunnan].

Objective: To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment. Methods: Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital. Results: The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men (P<0.001) and displayed a downward trend with age (P=0.03). The mutation rate of ethnic minorities was higher than Han (P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history (P<0.001), and patients without drinking history was higher than patients with drinking history (P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history (P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types (P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients (P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples (P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area (P<0.001). Multivariate analysis showed that gender (P<0.001), age (P=0.036), smoking history (P<0.001), pathological type (P<0.001), specimen type (P<0.001), and whether or not Xuanwei area (P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area (P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han (P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities (P=0.005). Conclusions: The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.

[Driver genes expression and clinical characteristics of targeted therapy in non-small cell lung cancer in Yunnan-Kweichow Plateau].

Objective: To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas. Methods: A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions. Results: The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender (P<0.001), smoking history (P<0.001), age (P<0.001), pathological type (P<0.001), and whether the Xuanwei area (P=0.027), but not related to the nationality (P=0.748) and family history of lung cancer (P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males (P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females (P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority (P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area (P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area (P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area (P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history (P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history (P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history (P=0.008). Conclusions: The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.

[Screening of colorectal cancer in Kunming urban residents from 2014 to 2017].

Objective: To explore the screening efficiency of colorectal cancer in urban residents of Kunming, China. Methods: Using the method of cluster sampling, from October 2014 to October 2017, residents of the three jurisdictions of Xishan, Guandu and Chenggong Districts of Kunming city were investigated. The inclusion criteria: (1) resident (for more than 3 years) population of Kunming city aged 40-74 years old; (2) voluntarily participating and receiving colonoscopy; (3) signing informed consent. Based on the Harvard Cancer Risk Index, the questionnaire was built on the consensus of more than 20 years of common cancer epidemiology in China. Through the consensus reached by the multidisciplinary expert panel discussion, a comprehensive evaluation system for cancer risk in China was designed. The high-risk group of colorectal cancer was determined by preliminary screening of the questionnaire, and a free colonoscopy was performed for the appointment to the gastrointestinal endoscopy department of the Yunnan Cancer Hospital. All polypoid lesions and ulcers found by colonoscopy must be biopsied to confirm the diagnosis. χ(2) test or Fisher exact probability method was used to compare the detection of colorectal cancer in 4 groups of 40-49 years old, 50-59 years old, 60-69 years old, and ≥70-years old. Detection of colonoscopy, compliance, pathological examination, pathological diagnosis, and morbidity of colorectal cancer were analyzed. Results: A total of 127 960 people from 40 to 74 years old of urban residents in Kunming city participated in the preliminary screening of the questionnaire, including 59 748 (46.7%) males and 68 212 females (53.3%) with mean age of (53.6±8.6) years old. The 40-49 years old group had the largest number of participants (48 044, 37.5%), followed by the groups of 50-59 years old (42 473, 33.2%), 60-69 years old (34 111, 26.7%), and ≥70 years old (3332, 2.6%). Till October 2017, a total of 14 971 people were screened as at high risk of colorectal cancer, with the high-risk detection rate of 11.7%, and the high-risk detection rate of women was significantly higher than that of men [13.4% (9 109/68 212) vs. 9.8% (5 862/59 748), χ(2)=386.947, P<0.001]. The highest high-risk detection rate was in the 50-59 years group in both gender [men: 11.1% (2202/19 831), women: 15.3% (3034/22 642)]. A total of 3449 people among the high-risk population received colonoscopy examination. The compliance rate of colonoscopy was 23.0% (3449/14 971), and the male compliance rate was 19.8% (1162/5862), which was significantly lower than that of females [25.1% (2287/9109), χ(2)=56.175, P<0.001]. The highest compliance was observed in the 50-59 years group [25.4% (1438/5668)], followed by 40-49 years and 60-69 year group [22.1%(1091/4931) and 22.0%(891/4048), respectively], and the compliance of ≥70 years old group was the lowest [9.0% (29/324)]. Colonoscopy examination revealed 606 cases with lesions, the detection rate of lesions was 17.6%, and the male detection rate was significantly higher than that of females [26.9% (313/1162) vs. 12.8% (293/2287), χ(2)=106.140, P<0.001]. The detection rate of lesions increased with age [40-49, 50-59, 60-69, ≥70: 10.9% (119/1091), 17.5% (252/1438), 25.0% (223/891) and 41.4% (12/29), respectively, χ(2)=79.010, P<0.001]. A total of 584 cases underwent endoscopic excision and pathological diagnosis, and 465 cases (13.5%) of precancerous lesions were detected. The prevalence of precancerous lesions in men was higher than that in women [21.3% (247/1162) vs. 9.5% (218/2287), χ(2)=90.801, P<0.001], the precancerous lesion detection rate increased with age [40-49, 50-59, 60-69, ≥70: 8.0% (87/1091), 14.3% (206/1438), 18.1% (161/891) and 37.9% (11/29); χ(2)=58.109, P<0.001]. A total of 4 patients with colorectal cancer were detected, including 3 males and 1 female. The detection rate of male colorectal cancer was 258.2/100 000, and the female was 43.7/100 000, whose difference was not statistically significant (χ(2)=1.488, P=0.223). There was no significant difference in the detection rate of colorectal cancer among 4 age groups [40-49, 50-59, 60-69, ≥70: 91.7/100 000 (1/1091), 69.5/100 000 (1/1438), 224.5/100 000 (2/891) and 0, respectively, P=0.696]. Conclusions: Screening for colorectal cancer is an important measure to control the onset and death of colorectal cancer. Through the questionnaire risk assessment plus colonoscopy, two-step screening method can improve the screening efficiency and greatly reduce the screening cost.

HOXA10 promotes nasopharyngeal carcinoma cell proliferation and invasion via inducing the expression of ZIC2.

OBJECTIVE: In this study, we aimed to explore the dysregulated genes in nasopharyngeal carcinoma (NPC) and to investigate the regulative effect of HOXA10 on ZIC2 expression and their involvement in NPC cell proliferation and invasion. MATERIALS AND METHODS: Microarray data that compared the transcription profile of NPC tissues and normal tissues was searched in GEO datasets and was re-analyzed. The expression of HOXA10 and ZIC2 mRNA were retrieved in TCGA database. CNE1 and CNE2 cells were used as an in-vitro cell model. Luciferase reporters carrying truncated ZIC2 promoter sequences were generated to verify the predicted HOXA10 binding site. CCK-8 assay and transwell assay were applied to assess cell proliferation and invasion respectively. RESULTS: HOXC6, HOXA3, and HOXA10 were upregulated in NPC tissues. Data mining in TCGA database showed that HOXA10, but not HOXC6 or HOXA3 is positively correlated to ZIC2 expression. Enforced HOXA10 expression significantly elevated ZIC2 expression at both mRNA and protein levels in both CNE1 and CNE2 cells. HOXA10 can directly bind to the promoter of ZIC2 and upregulate ZIC2 transcription. ZIC2 knockdown significantly reduced cell proliferation and invasion capability of CNE1 cells and also partly abrogated the effect of HOXA10 overexpression on enhancing cell proliferation and invasion. CONCLUSIONS: Both HOXA10 and ZIC2 are upregulated in NPC tissues compared to the normal tissues. HOXA10 can increase ZIC2 expression via binding to the ZIC2 promoter. Functionally, the HOXA10-ZIC2 axis can enhance NPC cell proliferation and invasion.

[The prevalence of ideal cardiovascular health metrics in Southeast Chinese middle-aged men].

Objective: To observe the prevalence and distribution of ideal cardiovascular health metrics in middle-aged men living in Su-Xi-Chang region and explore the relationship between health behavior and health factors. Methods: A total of 27 824 middle-aged men, who took part in health examination in the Center for Healthcare Management, Taihu Rehabilitation Hospital of Jiangsu Province from January 2014 to June 2015, were enrolled in this cross-sectional study. The ideal cardiovascular health metrics were defined by the American Heart Association criteria with minor modification in that the amount of vegetable intake was replaced by salt intake. The prevalence and distribution of ideal cardiovascular health metrics as well as the association between ideal cardiovascular health metrics and health factors were analyzed in this cohort. Results: The body mass index in the whole cohort was (25.1±3.0) kg/m2, waist circumference was (87.3±8.42) cm; the percent of subjects with all seven ideal cardiovascular health metrics was only 0.5% (n=133). The highest proportion of ideal metric was total cholesterol (68.5%, n=19 056), followed by fasting glucose (66.9%, n=18 616), body mass index (50.2%, n=13 963), physical exercise (45.6%, n=12 697), smoking (40.3%, n=11 216), blood pressure (22.5%, n=6 257) and salt intake (15.6%, n=4 351). The proportion of ideal cardiovascular health metrics reduced gradually and the proportion of poor cardiovascular health metrics status increased gradually with aging(χ2=106.746, P=0.000). The total cholesterol level of non-smokers was significantly lower than that of smokers(F=8.571, P=0.000); total cholesterol, blood pressure and fasting glucose levels increased in proportion with increasing body mass index(all P<0.01); total cholesterol and fasting blood glucose of subjects with regular active physical exercise were significantly lower than those with inactive physical exercise(all P<0.01); total cholesterol and blood pressure of subjects with high salt intake were significantly higher than those with low salt intake(all P<0.01). Conclusions: The proportion of subjects with ideal cardiovascular health metrics is very low in middle-aged men living in Su-Xi-Chang region, and the downtrend with poor cardiovascular health metrics increases with aging. Overweight or obese, smoking, high salt diet and poor control of blood pressure are the major cardiovascular risk factors in this cohort.

Good hydration and cell-biological performances of superparamagnetic calcium phosphate cement with concentration-dependent osteogenesis and angiogenesis induced by ferric iron.

The multifunctionality of calcium phosphate cement (CPC) can be achieved via co-doping with different metallic ions. Magnetism and hyperthermia have been proposed as potential therapeutic methods in bone healing and anti-osteosarcoma treatment. Iron-doping in biomaterials has been confirmed to meet the clinical requirements for these treatments. Herein, superparamagnetic iron-doped CPC (Fe-CPC) showed improved injectability and compressive strength, increased negative surface charge and accelerated hydration with increasing Fe3+ concentration. The superparamagnetism of Fe-CPC was confirmed through vibrating sample magnetometer (VSM) analysis. Mouse bone marrow stromal cells (mBMSCs) cultured on Fe-CPC disks exhibited better attachment morphology and proliferation, and had an enhancement of osteogenic-related gene expression. Moreover, a series of extracts with different concentrations of Fe3+ in cell culture medium were leaching-prepared to simulate the Fe3+-containing liquid environment around the magnetic biomaterials. The performances of mBMSCs and human umbilical vein endothelial cells (HUVECs) cultured in Fe3+-extracts showed increased proliferation rate in a certain amount of Fe3+. Osteogenesis and angiogenesis induced by Fe3+ were observed, but cytotoxicity in mBMSCs appeared when the concentration of Fe3+ was beyond a critical value. Fe-CPC is supposed to have prospective applications in bone remodeling through the combination of self-setting in situ, injectability, superparamagnetism, osteogenesis, angiogenesis, and osteoconductivity.

alpha-1,3-Fucosyltransferase-VII stimulates the growth of hepatocarcinoma cells via the cyclin-dependent kinase inhibitor p27Kip1.

After the transfection of alpha-1,3-fucosyltransferase (FucT)-VII cDNA into H7721 human hepatocarcinoma cells, the protein expression of some cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDIs) p16INK4 and p21waf1/Cip1 were unchanged. However, CDI p27Kip1 protein, both the total amount and the amount that bound to CDK2, but not its mRNA, was significantly reduced. The de-inhibited CDK2 stimulated the phosphorylation of retinoblastoma (Rb) protein and facilitated the G1/S transition and growth rate of the cells. The decrease of p27Kip1 protein, the increase of CDK2 activity and Rb phosphorylation, as well as the cell growth and percentage of S phase cells were correlated to the increased amount of cell surface sialyl Lewis X (SLe(x)) antigen in cells with different alpha-1,3-FucT-VII expression. The reduction in p27Kip1 and the difference in its expression among different transfected cells were blocked by the SLe(x) antibody KM93 in a dose-dependent manner, indicating that p27Kip1 expression was influenced by alpha-1,3-FucT-VII and its product SLe(x). The MEK/MAPK signaling pathway was more important than the PI-3K pathway in the regulation of p27Kip1 expression.

N-acetylglucosaminyltransferase V modifies the signaling pathway of epidermal growth factor receptor.

Transfection of sense cDNA of N-acetylglucosamyltransferase V (GnTV-S) into human H7721 hepatocarcinoma cells resulted in an increase in the N-acetylglucosaminebeta1,6mannosealpha1,3- branch (GnT-V product) on the N-glycans of epidermal growth factor (EGF) receptor (EGFR), and promotion of its EGF binding and tyrosine autophosphorylation, but showed little effect on the expression of EGFR protein. The phosphorylation at T308, S473 and tyrosine residue(s) and the activity of protein kinase B (Akt/PKB) as well as the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) before and after EGF stimulation were concomitantly increased. Conversely, in the antisense GnT-V (GnTV-AS)-transfected H7721 cells, all the results were the reverse of those with GnTV-S-transfected cells. After the cells were treated with 1-deoxymannojirimycin, an inhibitor of N-glycan processing at high mannose, or antibody against the extracellular glycan domain of EGFR, the differences in PKB activity, p42/44 MAPK and MEK phosphorylation among GnTV-S-, GnTV-AS- and mock-transfected cells were significantly attenuated. These findings indicate that the altered expression of GnT-V will change the glycan structure and function of EGFR, which may modify downstream signal transduction.

Modulation of the basal activity of phosphatidylinositol-3-kinase/protein kinase B signaling pathway in human hepatocarcinoma cells.

The modulation of GnT-V activity by signaling molecules in PI-3-K/PKB pathway in human hepatocarcinoma cell line 7721 was studied. GnT-V activity was determined after the transfection of sense or antisense cDNA of PKB into the cells, as well as the addition of activators, specific inhibitors, and the antibodies to the enzyme assay system or culture medium. It was found that the basal activity of GnT-V was up regulated by the sense and down regulated by the antisense cDNA of PKB transfected into 7721 cells. GnT-V was activated by PIP2, PIP3 or GTPgamma[S] added to the assay system, and the activation of PIP2 or GTPgamma[S] was abolished by LY2940002, a specific inhibitor of PI-3-K, but the activation of PIP3 was not attenuated by LY2940002. In addition, GnT-V activity in cultured parental or H-ras transfected cells was inhibited by the antibody against PKB or PI-3-K. These findings demonstrated the involvement of PI-3-K/PKB signaling pathway in the regulation of GnT-V. Moreover, ET18-OCH3, an inhibitor of Raf translocation and PI-PLC enzyme, which produces the activator of PKC, as well as the antibodies against Raf-1 or MEK also inhibited GnT-V activity in the parental and H-ras transfected cells. The inhibitory rates, however, were less in the transfected cells than those in the parental cells. These results reveal that in parental and H-ras transfected 7721 cells, the basal activity of GnT-V is also regulated by the Ras/Raf-1/MEK/MAPK cascade in addition to PI-3-K/PKB signaling pathway. The significance of these two pathways in the regulation of GnT-V and their relations to the activation of PKC previously reported by our laboratory (Ju TZ et al., 1995 Glyconjugate J 12, 767-772) was discussed.

[The electron probe microanalysis on oral precancer treated by garlic].

OBJECTIVE: To evaluate the effect of 4 kinds of trace elements on experimental oral precancer treated by garlic. METHODS: The palatal mucosae of 42 Wistar rats were painted with 0.5% of 4-nitroquinololine-1-oxide(4NQO) three times weekly for 7 weeks by coating method. Then the animals were divided randomly into two groups. The treatment group was treated three times weekly with garlic solution at the posterior hard palatal mucosae by coating method, and in the control group, the vehicle-distilled water was used instead of garlic solution. At the 5th and 8th weeks of the treatment and the 7th week after the treatment was stopped, some animals were killed. The palatal epithelial cells were prepared and surveyed by electron probe microanalysis. RESULTS: During the treating period, garlic improved the levels of epithelial cells' nuclei copper, selenium, molybdenum and extranuclei selenium, molybdenum(P < 0.01), but it decreased the contents of epithelial cells' extranuclei copper and extra- and intranuclei zinc(P < 0.01). CONCLUSIONS: Garlic can treat the oral precancer by improving the levels of epithelial cells' nuclei copper, selenium, and molybdenum and extranuclei selenium and molybdenum.

[Study on trace elements in epithelial cells during oral carcinogenesis prevented by garlic].

Sixty-two Wistar rats were divided randomly into two groups, thirty-one for each group. The posterior hard palatal mucosae of all animals were painted thrice weekly with 0.5% 4-nitroquinoline 1-oxide(dissolved in dimethyl sulfoxide). Before that, the garlic injection solution and the distilled water were painted at the same place of the experimental and control group animals, respectively. All animals were killed in turn from the beginning of the experiment at random at the 10th, 13th, and 19th week. Then, trace elements of intranuclear and cytoplasm of epithelial cells or cancer cells at the mentioned weeks were surveyed by electron probe microanalysis. The results were that garlic decreased the levels of intranuclear and cytoplasm copper(P < 0.05); the levels of intranuclear and cytoplasm selenium at the 10th week and the 13th week(P < 0.05) and those of zinc at the 19th week (P < 0.01) increased. So, garlic inhibits oral carcinogenesis by changing concentrations of intranuclear and cytoplasm trace elements that is copper, zinc, selenium, and the ratio of the three elements.

Effects of glutamine on tumor growth and apoptosis of hepatoma cells.

AIM: To explore the effects of glutamine on growth and apoptosis of hepatoma cells. METHODS: Mice inoculated with hepatoma cell (H22) suspension subcutaneously at right axilla were orally administered with glutamine (GLN) solution. Human hepatoma cell culture (SMMC-7721) was treated with different concentrations of GLN solution. The content of malondialdehyde (MDA) and nitric oxide (NO) was detected in mice plasma and cell culture, and that of glutathione (GSH) was decected in cells. The inoculated tumor's growth in the mice and hepatoma cells' proliferation and apoptosis were observed. RESULTS: When mice were administered orally with GLN solution (300 mg/kg), the growth of inoculated hepatoma was suppressed in the mice. When different concentrations of GLN solution were added in human hepatoma cell culture, the hepatoma cells' proliferation was inhibited and cells were induced to apoptosis, which was dependent on GLN concentration; meanwhile the contents of NO rose both in mice plasma and in cell culture, however MDA contents were slightly lowered in both, and the activity of GSH increased in the cells which had been ultrasonically shattered. CONCLUSION: Hepatoma cell apoptosis and tumor growth inhibition by GLN may be associated with its antioxidative activity and its intervention in hepatoma cell proliferation, and simultaneous release of NO.

N-acetylglucosaminyltransferase V activity in metastatic models of human hepatocellular carcinoma in nude mice.

N-linked beta 1-6 branched oligosaccharides may contribute directly to the malignant phenotype including metastatic potential of tumour cells. Increased beta 1-6 branching was associated with an increased level of N-acetylglucosaminyltransferase V (GnT V). In this report, the tissues from two metastatic models of human hepatocellular carcinoma (HCC) in nude mice were obtained. GnT V activity and mRNA level were determined. Results showed that GnT V activity in highly metastatic LCI-D20 models (Liver Cancer Institute, passage time: 20 days) (413.1+/-86.4U) was much higher than that in low metastatic LCI-D35 model (passage time 35 days) (155.3+/-31.9U). Northern blot showed that the mRNA level of GnT V in two models had no change. During the selection of a highly metastatic LCI-D20 model, GnT V activity increased from 301.6+/-57.3U to 413.1+/-86.4U while the highly metastatic LCI-D20 model acquired higher metastatic ability after selection. When highly metastatic LCI-D20 model tissues were implanted subcutaneously (s.c.), the GnT V activity decreased dramatically from 413.1+/-86.4U to 94.9U. This is the first report that GnT V activity increased in HCC during metastasis in vivo.

Restoration of the p16 gene is related to increased radiosensitivity of p16-deficient lung adenocarcinoma cell lines.

To assess the role played by p16 gene expression in the radiosensitivity of human lung cancers, we transferred exogenous p16 genes into p16-deficient H460 and A549 lung adenocarcinoma cell lines and compared the cell survival curve in vitro after irradiation. The surviving fraction of the p16-transfected A549p16 and H460p16 cells that expressed exogenous p16 mRNA or protein was lower than those of the parental and negative control cells. The rapid exit of the p16-transfected cells from the G2/M phase in the cell cycle, both before and after irradiation, possibly contributes to the increased radiosensitivity of our experimental p16-transfected lung adenocarcinoma cell lines. We conclude that exogenous p16 gene may be another important factor controlling the intrinsic cellular radiosensitivity of cancer.