[Efficacy and safety of new systemic therapies in moderate-to-severe atopic dermatitis in the elderly: meta-analysis].

Objective: To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis. Methods: The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio (OR) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed. Results: A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients (OR=0.79, 95%CI:0.58-1.07, P=0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients (OR=0.79, 95%CI:0.55-1.14, P=0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients (OR=1.07, 95%CI:0.65-1.77, P=0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related. Conclusion: The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

[Investigation on health status of workers exposed to glyphosate].

Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively (P<0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine (r(s)=0.804, 0.238, P<0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine (r(s)=0.549, P<0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different (P<0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group (P<0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.

[The value of immunohistochemical expression of Ki-67 and CD34 in differentiating ductal carcinoma in situ from ductal carcinoma in situ-like invasive breast cancer].

Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS (P<0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant (P<0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.

Genetic Polymorphism and Forensic Application of 47 Autosomal InDel Loci in 5 Chinese Ethnic Groups.

ABSTRACT: Objective To investigate the population genetic data of 47 autosomal insertion/deletion （InDel） polymorphism genetic markers involved in AGCU InDel 50 kit in Guangdong Han, Guangxi Zhuang, Guangxi Yao, Guangxi Jing, and Guangxi Mulam, and to evaluate their application in forensic DNA identification. Methods Multiplex amplification of the 768 unrelated individuals from the 5 ethnic groups mentioned above was performed with the AGCU InDel 50 kit. Genotyping was carried out by 3500xL gene analyzer, population genetic parameters were gathered and polymorphism analysis was performed. Results No linkage disequilibrium was found among 47 autosomal InDel loci in the 5 ethnic groups. The distribution of genotype frequency of 47 autosomal InDel loci confirmed to the Hardy-Weinberg equilibrium in Guangdong Han and Guangxi Zhuang. Except for rs139934789, the other 46 loci confirmed to the Hardy-Weinberg equilibrium in Guangxi Yao, Guangxi Jing, and Guangxi Mulam. The results of genetic variation analysis among the populations showed that 1.12% of genetic variation was caused by ethnic group differences. The cumulative discrimination power of 47 autosomal InDel loci for the 5 ethnic groups were all above 0.999 999 999 999 999. The cumulative probability of exclusion for each ethnic group was less than 0.999 9. The two Y-InDels were identified in all male individuals and were absent in all female individuals. Conclusion Except for rs139934789, the other 46 InDel loci have a relatively good genetic polymorphism in the 5 Chinese ethnic groups, and can be used for forensic individual identification and as effective supplements for paternity testing.

PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD.

AIM: We aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. MATERIALS AND METHODS: We enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a 'strict-normal' TSH group (TSH level 0.4 to 2.5mIU/L; n=283) and a 'high-normal' TSH group (TSH level 2.5 to 5.3mIU/L with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes. RESULTS: Compared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298-8.284; P=0.012). CONCLUSION: In euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.

Correlations between CXCL13, IL-24 genes and wrist arthritis.

OBJECTIVE: To investigate the relationship between B lymphocyte chemokine 1 (CXCL13) and interleukin-24 (IL-24) gene and wrist arthritis. PATIENTS AND METHODS: A total of 122 cases of patients with wrist arthritis treated in our hospital from May 2013 to April 2016 were randomly selected as wrist arthritis group, while 120 normal subjects were selected as normal control group. Venous blood was collected from all patients in normal control group and wrist arthritis group, respectively. Rheumatoid factor (RF), human C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in venous blood were measured. The visual analogue scale (VAS) score was used to statistically analyze the pain of subjects in normal control and wrist arthritis groups; the wrist flexion and extension activities of subjects in normal control group and wrist arthritis group were measured. The expressions of CXCL13 and IL-24 mRNA in synovial tissue of normal control group and wrist arthritis group were detected by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was used to detect the expressions of CXCL13 and IL-24 in normal control group and wrist arthritis group. RESULTS: The levels of CRP, RF, and ESR in the normal control group were within the normal range, but the levels of CRP, RF, and ESR in the wrist arthritis group were significantly higher than those in the normal control group. VAS scores and joint flexion extension activities in the normal control group were at normal levels. The VAS score of wrist arthritis group was significantly higher than that of the normal control group, and the joint flexion extension activities were significantly lower than that in the normal control group. The results of RT-PCR showed that the expression of CXCL13 mRNA in synovial tissue of wrist arthritis was significantly higher than that in the normal control group, while the expression of IL-24 mRNA in synovial tissue of wrist arthritis was significantly lower than that in normal control tissues. Western blotting showed that the expression of CXCL13 in synovial tissue of wrist arthritis was significantly higher than that in the normal control group, while the expression of IL-24 in synovial tissue of wrist arthritis was significantly lower than that in normal control groups. Analysis of variance showed that the expressions of CXCL13 and IL-24 in the normal control group and wrist arthritis group had statistically significant differences (p<0.01). CONCLUSIONS: The abnormal expressions of CXCL13 and IL-24 are closely related to the occurrence and development of wrist arthritis. This study shows that CXCL13 and IL-24 have important research values in wrist arthritis. CXCL13 and IL-24 expressions can be used as new indicators of the diagnosis and treatment of wrist arthritis.

The antitumor efficacy of anti-p21Ras scFv mediated by the dual-promoter-regulated recombinant adenovirus KGHV300.

Ras mutations and overexpression of the Ras protein, p21Ras, are main causes of cancer development and progression, which has made the Ras gene and p21Ras important targets for therapy of Ras-driven cancers. We previously prepared recombinant adenovirus KGHV100 based on replication-defective adenovirus type 5, which could intracellularly express anti-p21Ras single chain fragment viable antibodies (scFv) and repress tumor growth in vitro and in vivo. However, the anti-tumor effects of this anti-p21Ras scFv were limited by short-term scFv expression due to a replication defect of KGHV100. To enhance the anti-tumor efficacy and safety of anti-p21Ras scFv, the present study constructed a dual-promoter-regulated recombinant adenovirus KGHV300 that carried anti-p21Ras scFv. In KGHV300, the expression levels of the essential replication genes E1a and E1b, were controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively, and the anti-p21Ras scFv gene was controlled by the cytomegalovirus promoter. The conditional replication of KGHV300 and its antitumor efficacy were characterized in several tumor cell lines in vitro and in xenograft models of human breast cancer in nude mice. TCID50 assay demonstrated that KGHV300 could replicate in tumor cell lines but not in normal cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay indicated that the growth of tumor cells was effectively inhibited by KGHV300 infection. In MDA-MB-231 tumor xenograft models, KGHV300 effectively and significantly inhibited tumor growth and induced apoptosis of tumor cells. We concluded that the recombinant adenovirus KGHV300 may be a more potent and safer antitumor therapeutic for Ras-driven cancer biotherapy.

[Mutation status of epidermal growth factor receptor and KRAS gene in non-small cell lung cancers at Xuanwei regions of Yunnan Province].

OBJECTIVE: To investigate the mutation status of epidermal growth factor receptor (EGFR) and KRAS gene in patients with non-small cell lung cancer (NSCLC) in Xuanwei, Yunnan and to correlate the mutation status with clinicopathologic features. METHODS: Mutation status of exons 18, 19, 20 and 21 of EGFR, and codons 12, 13 of KRAS in 63 cases of NSCLC were analyzed by gene sequencing and ARMS-Taqman probe method. Correlation with patients' clinicopathological characteristics was performed. RESULTS: EGFR and KRAS mutations were present in 55.6% (35/63) and 6.3% (4/63), respectively. EGFR gene mutations were present, including exon 18 G719X in 14.3% (5/35), exon 19 in 14.3% (5/35), exon 20 S768I and T790M in 20.0% (7/35), exon 21 L858R in 31.4% (11/35), exon 18 G719X and exon 20 S768I double mutation in 17.1% (6/35), and exon 20 T790M and exon 21 L858R double mutation in 2.9% (1/35). KRAS mutations were seen in codon 12 in 3 of 4 cases, and codon 13 in 1 of 4 cases. EGFR mutations were mutually exclusive with KRAS mutations. According to statistic analysis, EGFR mutations were associated with the histological types of NSCLC(P<0.05), but without correlation with patient's gender, age, smoking status and lymph node metastasis(P>0.05). KRAS mutations in NSCLC had no correlation with the clinical pathologic characteristics of the patients. CONCLUSIONS: A higher frequency of EGFR exon 18 G719X and 20 exon S768I mutations are found in the patients in Xuanwei, Yunnan. EGFR mutations are associated with histologic types of NSCLC, but without correlation with patient's gender, age, smoking status and lymph node metastasis. KRAS mutation in NSCLC has no correlation with the clinicopathologic characteristics of the patients.

Effect of HIF-1a/VEGF signaling pathway on plasma progesterone and ovarian prostaglandin F2a secretion during luteal development of pseudopregnant rats.

The corpus luteum is a temporary endocrine structure in mammals that plays an important role in the female reproductive cycle and is formed from a ruptured and ovulated follicle with rapid angiogenesis. Vascular endothelial growth factor (VEGF) is thought to be vital in normal and abnormal angiogenesis in the ovary, but the molecular regulation of luteal VEGF expression during corpus luteum development in vivo is still poorly understood at present. Therefore, we examined whether hypoxia-inducible factor-1a (HIF-1a) is induced and regulates VEGF expression and luteal function in vivo using a pseudopregnant rat model treated with a small-molecule inhibitor of HIF-1a, echinomycin. Corpus luteum development in the pseudopregnant rat ovary was determined after measuring plasma progesterone concentration and ovarian prostaglandin F2a content to reflect changes in HIF-1a and VEGF on different days of this developmental process. At day 7, the corpus luteum was formed and the expression of HIF- 1a/VEGF reached a maximum, while a significant decrease in HIF-1a/ VEGF expression was observed when luteolysis occurred at day 13. Additionally, echinomycin blocked luteal development by inhibiting VEGF expression mediated by HIF-1a and following luteal function by detecting the progesterone changes at day 7. These results demonstrated that HIF-1a-mediated VEGF expression might be an important mechanism regulating ovarian luteal development in mammals in vivo, which may provide new strategies for fertility control and for treating some types of ovarian dysfunction, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, and ovarian neoplasia.

Upgrades of imaging x-ray crystal spectrometers for high-resolution and high-temperature plasma diagnostics on EAST.

Upgrade of the imaging X-ray crystal spectrometers continues in order to fulfill the high-performance diagnostics requirements on EAST. For the tangential spectrometer, a new large pixelated two-dimensional detector was deployed on tokamaks for time-resolved X-ray imaging. This vacuum-compatible detector has an area of 83.8 × 325.3 mm(2), a framing rate over 150 Hz, and water-cooling capability for long-pulse discharges. To effectively extend the temperature limit, a double-crystal assembly was designed to replace the previous single crystals for He-like argon line measurement. The tangential spectrometer employed two crystal slices attached to a common substrate and part of He- and H-like Ar spectra could be recorded on the same detector when crystals were chosen to have similar Bragg angles. This setup cannot only extend the measurable Te up to 10 keV in the core region, but also extend the spatial coverage since He-like argon ions will be present in the outer plasma region. Similarly, crystal slices for He-like iron and argon spectra were adopted on the poloidal spectrometer. Wavelength calibration for absolute rotation velocity measurement will be studied using cadmium characteristic L-shell X-ray lines excited by plasma radiation. A Cd foil is placed before the crystal and can be inserted and retracted for in situ wavelength calibration. The Geant4 code was used to estimate X-ray fluorescence yield and optimize the thickness of the foil.

Percutaneous quadriceps tendon pie-crusting release of extension contracture of the knee.

To release extension contracture of the knee, the authors used a minimally invasive technique: percutaneous quadriceps tendon pie-crusting release. Percutaneous pie-crusting release was performed using an 18-gauge needle to puncture the stiff fibrous band of the distal and lateral quadriceps tendon under maximum knee flexion. Quadriceps contracture was gradually released by multiple needle punctures. A knee brace was prescribed for one week and knee flexion exercises were performed on the first postoperative day. This technique was performed in seven post-traumatic stiff knees and five stiff total knee arthroplasties. Mean maximum flexion increased from 37° preoperatively to 50° after arthrolysis and 107(o) after pie-crusting. At a mean follow-up of eight months, mean maximum flexion was 103°. There were no major complications. The technique of quadriceps tendon pie-crusting release is a simple, minimally invasive and effective treatment for knee extension contracture.

Antioxidant enzyme levels in pathogenesis of oral squamous cell carcinoma (OSCC).

Increased oxidative stress and altered anti-oxidant defense systems have been implicated in the pathogenesis of several diseases including cancer. Therefore, the aim of our study is to evaluate the antioxidant enzyme levels such as superoxide dismutase (SOD) and catalase in blood samples and tissues collected from oral squamous cell carcinoma patients and compared with healthy controls.The collected blood samples and tumor tissues from the diseased individuals and the normal controls are analyzed for malondialdehyde (MDA) and nitric oxide (NO), which is the indicator of oxidative and nitrosative stress respectively. The anti-oxidant enzymes SOD and catalase levels are measured by UV visible spectrophotometer. Subsequently, immuno-histostaining for antioxidant enzymes were performed in oral squamous cell carcinoma biopsies and sections were analyzed.The levels of MDA and NO were significantly elevated in the blood and tissue samples of OSCC patients. The antioxidant enzymes SOD and catalase were significantly reduced in OSCC tissues; while in erythrocytes catalase level is reduced whereas the SOD level is increased. Further, the reduced immuno-histostaining was observed for catalase and SOD in OSCC tissues when compared to normal oral epithelium.The enhanced levels of MDA and NO revealed that increased oxidative stress in conjunction with the reduced antioxidant defense mechanism in OSCC patients, might be involved in cancer progression. Our results suggest that detection of reactive oxygen species (ROS) and antioxidant enzymes levels might be a valuable marker in cancer prognosis and for improving therapeutic strategies in oral cancer.

Changes in blood oxidative and antioxidant parameters in a group of Chinese patients with age-related macular degeneration.

OBJECTIVE: To measure the oxidative and antioxidant biochemical parameters in the serum of Chinese patients with age-related macular degeneration (AMD) and in a similar age control group from the same area. DESIGN: A case-control study. PARTICIPANTS: 56 AMD patients ( 21 early dry, 13 geographic atrophy and 22 wet form) and 34 normal subjects, similar for age and sex were studied. MEASUREMENTS: Both groups completed a questionnaire about demographic characters and dieatry habit, and the levels of serum lipid peroxidation (malondialdehyde, MDA) and antioxidants parameters (vitamin C and E, the activities of superoxide dismutase--SOD, total antioxidant capacity--TAC ) were determined. RESULTS: There was a significantly higher frequency of daily intake of fruit and legumes in controls than in AMD patients. There was a significantly increased serum MDA levels and SOD activities, and significantly decreased serum vitamin C and total antioxidant capacity in AMD patients as compared to controls. The intensity of lipid peroxidation was higher with the progression of AMD. There was not difference in serum vitamin E levels between AMD patients and controls. CONCLUSION: Oxido-reduction disturbance may be involved in the pathogenesis of AMD. There is a significantly decreased antioxidant capacity in AMD patients.

Effects of fasting on hematologic and clinical chemical values in cynomolgus monkeys (Macaca fascicularis).

BACKGROUND: Fasting is an important pre-analytical factor that may affect clinical pathology parameters in toxicological and pharmacological studies. Little information is available on how fasting affects clinical pathology parameters in cynomolgus monkeys (Macaca fascicularis).The aim of this study was to evaluate the influence of fasting on clinical pathology parameters in healthy adult cynomolgus monkeys. METHODS: Five female and six male cynomolgus monkeys were fasted for 0, 8, 16, and 24 hours. Changes in body weight (BW), core hematologic, and serum clinical chemical parameters were evaluated. RESULTS: The BW significantly decreased after 24 hours of fasting. Significant decreases in red blood cell count, hemoglobin, hematocrit, and mean corpuscular volume and increases in mean cell hemoglobin and mean cell hemoglobin concentration were observed at 16 hours in males. In females, increasing the duration of fasting caused a significant time-dependent increase in platelets. Blood urea nitrogen showed significant decreases in female and male monkeys after fasting. Alkaline phosphatase increased in females after fasting. Aspartate transaminase significantly increased both in females and males at 8 hours. In females, alanine transaminase and lactate dehydrogenase significantly increased at 8 hours. Albumin significantly decreased in males 24 hours, but increased in females 16 hours after fasting. Serum glucose and triglyceride were not affected by fasting. Serum calcium decreased and inorganic phosphorus increased in males after fasting. CONCLUSION: These results suggested that clinical pathology data would vary after fasting. The decision to feed or fast before blood collection for clinical pathology tests should be made based on careful consideration.

Expression of claudin-3 and claudin-4 in normal, hyperplastic, and malignant endometrial tissue.

To clarify the roles of claudins in endometrial tumorigenesis, we determined levels of protein and messengerRNA (mRNA) expression of claudin-3 and claudin-4 in human endometrial tissue (proliferative phase [PE, n= 25]; secretory phase [SE, n= 25]; simple hyperplasia [SH, n= 20]; complex hyperplasia [CH, n= 12]; atypical hyperplasia [AH, n= 15]; endometrioid adenocarcinoma [EEC, n= 30]) using immunohistochemistry, western blotting, and real-time polymerase chain reaction, respectively. Morphologic changes of tight junctions (TJs) were also observed in normal, hyperplastic, and malignant endometrial tissue. Absence or weak staining for claudin-3 and claudin-4 was observed in PE, SE, SH, and CH, while medium to intense staining was detected in AH and EEC. Staining of claudin-3 and claudin-4 was predominantly localized to the glandular epithelial cell membrane. Expression of claudin-3 and claudin-4 was significantly increased in the groups of AH and EEC in comparison with the groups of CH, SH, and normal cyclic endometrium at both protein and mRNA levels. The highest expression was observed in EEC. Although no relevance was found with regard to FIGO stage and histologic grade, overexpression of claudin-3 and claudin-4, especially claudin-4, significantly correlated with myometrial invasion. Transmission electron microscopy analysis indicated morphologic disruptions of TJs may lag behind the increase of claudins expression. These results demonstrate that claudin-3 and claudin-4 are strongly expressed in AH and EEC, but less frequently in normal endometrium. The upregulation of claudins expression during endometrial carcinogenesis suggests their potential utility as diagnostic and prognostic biomarkers.

Population-based, case-control study of blood C-peptide level and breast cancer risk.

Insulin resistance has been suggested to be associated with an increased risk of breast cancer. Insulin sensitivity can be measured using blood C-peptide, a marker of insulin secretion. It is thus conceivable that blood C-peptide levels may be associated with breast cancer risk. To evaluate this hypothesis, we analyzed data from a subset (143 case-control pairs matched by age and status of menopause) of women who participated in the Shanghai Breast Cancer Study, a population-based, case-control study conducted in Shanghai during 1996-1998. Fasting blood samples were collected from study subjects to measure C-peptide levels. For cancer patients, the samples were collected before any cancer therapy. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals related to C-peptide levels. Breast cancer risk was increased with increasing levels of C-peptide (trend test, P = 0.01), with an odds ratio of 2.7 (95% confidence interval = 1.2-5.9) observed for the highest compared with the lowest tertile of C-peptide concentration after adjusting for body mass index and age at the first live birth. The risk was not altered after fully adjusting for other traditional risk factors for breast cancer. This positive association was observed in both pre and postmenopausal women and regardless of the levels of waist-to-hip ratio or body mass index. The results from this study were consistent with the insulin-resistance hypothesis for breast cancer and suggest that increased levels of C-peptide may contribute to the development of breast cancer.

[Clinical study on treatment of chemo- or radiotherapy induced leukopenia with fuzheng compound].

The therapeutic effect of Fuzhen Compound, a Chinese herbal medicine, on leukocyte count in 59 patients with cancer of advanced stage after chemo-or radiotherapy were observed. Among 41 cases with leukopenia before treatment, leukocyte of 37 cases were normalized after treatment, the count pre-and post-treatment were (2.8 +/- 0.6) x 10(9)/L and (5.9 +/- 1.4) x 10(9)/L respectively (P < 0.01). In 18 patients with normal leukocyte count before treatment, the counts of 17 cases were still kept in normal after treatment. The time for leukcoyte recovering was 8.0 days in average, while that of 23 patients did not take Fuzhen Compound was 20.6 +/- 1.8 days. The results indicated that the Fuzhen Compound could alleviate the inhibition of chemo-or radiotherapy on hemopoietic function of bone marrow and has leukocytogenic effect.