[Screening for Lynch syndrome in colorectal cancer].

OBJECTIVE: To evaluate the application of mismatch repair (MMR) genes proteins expression to screen for Lynch syndrome in colorectal cancer patients. METHODS: One hundred consecutive colorectal cancers cases collected from 2012 to 2013 were tested immunohistochemically for the protein expression of MLH1, MSH2, MSH6 and PMS2, and also by the ARMS method for the mutation status of BRAF genes in those cases lacking protein expression for MLH1. RESULTS: The result of MMR immunocytochemistry showed that nine of 100 cases lacked MMR protein expression, including three cases each that were MLH1-/PMS2- and MSH2-/MSH6- respectively, two cases were MLH6- and one case was PMS2-; overall, the majority of these cases lacked protein expression of MLH1 and MSH2. The BRAF genes mutation test showed one case of mutation, indicating that the patient might have MLH1 gene methylation as a result of the mutation of BRAF genes, and that was a sporadic case. The age of onset for patients lacking MMR protein expression was lower than patients with sporadic colorectal cancer (P = 0.011). Colorectal cancers associated with the lack of MMR protein expression mostly occurred in the right colon (P = 0.001), and histomorphologically were often accompanied by mucinous adenocarcinoma (P = 0.010) and tumor lymphocytic infiltration. CONCLUSION: Immunohistochemical staining for MMR proteins in patients with colorectal cancer, accompanied by testing for BRAF genes mutation, may be an effective approach to screen for Lynch syndrome.

Mechanism of Hirudin-Mediated Inhibition of Proliferation in Ovarian Cancer Cells.

To investigate the inhibitory effect of hirudin on the cell proliferation of human ovarian cancer A2780 cells by preventing thrombin and its underlying molecular mechanism. Cell Counting Kit-8 (CCK-8) method was used to detect the effect of different concentrations of hirudin and thrombin on the cell proliferation of A2780 cells. PAR-1 wild-type overexpression plasmid was constructed utilizing enzyme digestion identification, and it was transferred to A2780 cells. Sequencing and Western blot were used to detect the changes in PAR-1 protein expression. Western blot detection of PKCα protein phosphorylation in A2780 cells was performed. We also implemented quantitative PCR to detect the mRNA expression levels of epithelial-mesenchymal transition (EMT)-related genes, CDH2, Snail, and Vimentin, in A2780 cells. 1 µg/ml hirudin treatment maximally inhibited the promotion of A2780 cell proliferation by thrombin. Hirudin inhibited the binding of thrombin to the N-terminus of PAR-1, hindered PKCα protein phosphorylation in A2780 cells, and downregulated the mRNA expression levels of CDH2, Snail, and Vimentin. In conclusion, hirudin inhibits the cell proliferation of ovarian cancer A2780 cells, and the underlying mechanism may be through downregulating the transcription level of EMT genes, CDH2, Snail, and Vimentin. This study indicates that hirudin may have a therapeutic potential as an anti-cancer agent for ovarian cancer.

Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses.

Background: Growing evidence suggests that headache disorders and atopic dermatitis share similar pathological mechanisms and risk factors. The aim of this study was to assess the risk for headache disorders in patients with atopic dermatitis. Methods: We systematically searched the PubMed and Embase databases from inception to December 1, 2023, for observational studies that examined risk of migraine in subjects with atopic dermatitis. Risk estimates from individual studies were pooled using random-effects models. Results: Ten studies with 12,717,747 subjects were included in the meta-analysis. Our results showed that patients with atopic dermatitis were associated with a higher risk of headache disorder (OR, 1.46, 95% CI = 1.36-1.56; P < 0.001; I2 = 98%) or migraine (OR, 1.32, 95% CI = 1.18-1.47; P < 0.001; I2 = 98.9%). Most of the results of the subgroup analyses were consistent with the overall results. Conclusion: The findings of this meta-analysis suggest that atopic dermatitis is a potential risk indicator for headache disorder or migraine. Further studies are still needed to verify our findings due to the substantial heterogeneity in our analyses.

Microscopic Colitis Is Associated With a Reduced Risk of Colorectal Adenoma and Cancer: A Meta-Analysis.

BACKGROUND: The study sought to conduct a systematic review and meta-analysis of the risk of colorectal adenoma or cancer in patients with microscopic colitis (MC). METHODS: A comprehensive literature search of PubMed and EMBASE databases was performed. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to examine the effect of MC on the risk of colorectal adenoma or cancer. RESULTS: Twelve studies reporting the outcomes of 50 795 patients with MC were eligible for this meta-analysis. MC was negatively associated with the risk of colorectal adenoma compared with participants without MC (RR, 0.44; 95% CI, 0.33-0.58; P < .001; I2 = 87.3%). Also, the rate of colorectal cancer was lower in the patients with MC compared with the general population (RR, 0.62; 95% CI, 0.43-0.89; P = .01; I2 = 91.6%). In addition, sensitivity and subgroup analyses indicated that the results were robust. CONCLUSIONS: The present systematic review indicated that patients with MC may be associated with a lower risk of colorectal adenoma or cancer. The clinical data support the current professional society guideline. A surveillance colonoscopy program is not recommended as standard for patients with MC.

Patients with microscopic colitis (MC) are less likely to have colon adenomas or cancer compared with those without MC, supporting the recommendation of the professional society to the effect that patients with MC do not require colonoscopic surveillance.

Aerobic exercise improves adipogenesis in diet-induced obese mice via the lncSRA/p38/JNK/PPARγ pathway.

Adipogenesis is one of the triggers of obesity, which is a risk factor for various metabolic diseases. Long noncoding RNA steroid receptor RNA activator (lncRNA-SRA) is closely related to adipogenesis and p38/JNK mitogen-activated protein kinase mediates lipid production by regulating peroxisome proliferator-activated receptor gamma (PPARγ). Aerobic exercise can be efficient in improving adiposity and losing weight. Hence, we hypothesize that aerobic exercise ameliorates obesity by affecting the SRA/p38/JNK/PPARγ pathway and downstream target genes. The broad approaches used to test hypotheses are as follows. Spectrophotometer detected C57BL/6J mice blood lipid level; hematoxylin and eosin-stained fat tissue to check the grade of epididymis fat; quantitative polymerase chain reaction and Western blot detected messenger RNA expression and protein levels. Injected lncRNA-SRA virus vector to overexpress SRA. After 8 weeks of aerobic exercise intervention, obese mice showed significant improvements in body weight, white fat weight, lipid levels, and the Lee index. Aerobic exercise significantly inhibited the expression of SRA, activated the p38/JNK signaling pathway, further inhibited the expression of PPARγ and downstream target genes, and improved obesity. Aerobic exercise intervention improved lipid metabolism in obese mice, and the mechanism may be related to the regulation of the LncSRA/p38/JNK/PPARγ signaling pathway.

Temperature-triggered fluorocopolymer aggregate coating switching from antibacterial to antifouling and superhydrophobic hemostasis.

The multifunction antibacterial hemostatic materials can reduce blood loss, infection and wound complications, which probably decrease morbidity and health care costs. However, the contradictory relationship between antibacterial ability and biocompatibility, and the unnecessary blood loss restricts the practical application of hydrophilic cationic antibacterial hemostatic materials. Herein, a multifunctional temperature-triggered antibacterial hemostatic fluorocopolymer aggregate coating was developed. After self-assembly and quaternization process, the quaternized poly(N,N-dimethylaminoethylmethacrylate)-b-poly(1H,1H,2H,2H-heptadecafluorodecyl acrylate) block copolymers (PDMA-b-PFOEMA) aggregate coating consisting of fluoropolymer and quaternary ammonium salt were built. The synergistic effect on fluorinated block with low surface energy and quaternary ammonium salt block with bactericide activity severs the way of initial bacterial attachment and proliferation, while the migration of fluorinated block greatly promotes the biocompatibility and anti-adhesion performance in response to the switch from room temperature to physiological temperature. Furthermore, the fluorocopolymer aggregate coating with hydrophobic properties possessed the property of rapid coagulation, low blood loss, minor secondary bleeding and least bacteria infiltration. The multifunctional temperature-triggered fluorocopolymer aggregate coating with antifouling, antibacterial and hemostatic properties may have a great potential in the biomedical application.

Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Objective: To investigate the association between pretreatment prognostic nutritional index (PNI) and clinical survival outcomes for advanced-stage cancer patients treated with immune checkpoint inhibitors (ICIs). Methods: We conducted a comprehensive literature search to identify eligible studies concerning the relationship between pretreatment PNI and survival outcomes in advanced cancer patients treated with ICIs. Published data were extracted and pooled odds ratio (pOR) for objective response rate (ORR), disease control rate (DCR), and pooled hazard ratio (pHR) for overall survival (OS), progressive-free survival (PFS), along with 95% confidence intervals (95% CIs) were calculated. Results: Twelve studies with 1,359 participants were included in our study. A higher level of PNI indicated a greater ORR (pOR = 2.17, 95% CI = 1.52-3.10) and favorable DCR (pOR = 2.48, 95% CI = 1.87-3.29). Low PNI was associated with a shorter OS (pHR = 2.24, 95% CI = 1.57-3.20) and unfavorable PFS (pHR = 1.61, 95% CI = 1.37-1.88). Conclusion: Low PNI might be an effective biomarker of poor tumor response and adverse prognosis of advanced cancer patients with ICIs. Further studies are needed to verify the prognostic value of PNI in clinical practice.

Zusanli (ST36) Acupoint Injection With Dexamethasone for Chemotherapy-Induced Myelosuppression: A Systematic Review and Meta-Analysis.

OBJECTIVE: Myelosuppression is the most common adverse reaction of chemotherapy, which seriously affects the course of treatment. Zusanli (ST36) acupoint injection with dexamethasone has achieved good clinical efficacy in China. This study aimed to systematically evaluate the efficacy of ST36 acupoint injection with dexamethasone in the treatment of chemotherapy-induced myelosuppression (CIM). METHODS: Randomized controlled trials of CIM treated with ST36 acupoint injection with dexamethasone were retrieved from eight electronic databases. We used the Cochrane Collaboration tool to assess the risk of bias. Excel 2010 was used to establish a database for information extraction, and RevMan 5.3.0 software was used to analyze the included test data. GRADE profiler 3.6 software was used to grade the quality of evidence for the outcome indicators of the study. RESULTS: A total of 17 studies involving 1177 patients were included in this meta-analysis. The results showed that, compared with conventional western medicine (CWM), ST36 acupoint injection with dexamethasone could significantly improve the clinical total effective rate [RR=1.95, 95% CI (1.53, 2.49), P <0.00001] and increase white blood cell (WBC) (MD=1.38, 95% CI (0.74, 2.01), P<0.0001) and hemoglobin (Hb) levels [MD=3.89, 95% CI (1.57, 6.20), P=0.001]. In addition, ST36 acupoint injection with dexamethasone can shorten recovery time of myelosuppression [MD=-3.94, 95% CI (-4.97 to -2.91), P<0.00001] and improve Karnofsky performance status [MD=10.7, 95% CI (1.36, 20.05), P=0.02<0.05]. However, there was no significant difference among ST36 acupoint injection with dexamethasone and CWM in platelet (PLT) elevation [MD=4.61, 95% CI (-10.14, 19.35), P=0.54]. CONCLUSION: This study found that ST36 acupoint injection with dexamethasone had a positive effect on CIM. However, more studies with well-designed, large sample size, strict randomization, and clear descriptions about detection and reporting processes are needed in the future to further confirm the efficacy of ST36 acupoint injection with dexamethasone in the treatment of CIM. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/, identifier CRD42021223979.

[Expression and their clinical significance of SSTR2A, SSTR5 and EGFR in non-small cell lung cancer].

BACKGROUND: Somatostatin receptor (SSTR), as a marker gene in tumors, is being valued gradually. With five subtypes have been identified, many researches are carried out to explore the amino acid sequence of SSTR family members, the molecular biological characteristics, the distribution and expression in the normal tissue and the tumor, and their specific ligands. In this study, the expression and significance of SSTR (SSTR2A, SSTR5) and epidermal growth factor receptor (EGFR) in human non-small cell lung cancer (NSCLC) were investigated, and the relationship among them were evaluated. METHODS: The expressions of SSTR2A, SSTR5 and EGFR in 62 NSCLC tissues and 7 lung tissues adjacent to the cancer tissues were detected by immunohistochemical method (SP method). All cases were followed up. RESULTS: In 62 cases of NSCLC, the positive rate of SSTR2A and SSTR5 expression was 48.4% (30/62) and 71.0% (44/62) respectively. The positive rate of SSTR2A and SSTR5 was closely related to TNM stage (P < 0.05), but not to other clinical characteristics of NSCLC (P > 0.05). The positive rate of EGFR expression was 56.5% (35/62), but 0 in 7 lung tissues adjacent to the cancer tissues. The positive rate of EGFR was not related to the age, sex, smoking or not, tumors histological type, tumor size, TNM stage, differentiation classification and the lymph node metastasis (P > 0.05). There was negative relation between the expression of SSTR2A, SSTR5 and EGFR in NSCLC. The 3-year survival rate of patients with SSTR2A and SSTR5 expression was 64.52% and 65.91% respectively, 45.16% and 22.22% for those without expression (P < 0.05); The 3-year survival rate of patients with EGFR expression was 30.77% and 69.44% for those without expression (P < 0.05 ). CONCLUSIONS: The expression of SSTR and EGFR is significantly upregulated in NSCLC and a negative relation exists between their expressions. Detection of expression of SSTR2A, SSTR5 and EGFR might be helpful to evaluate lymph node metastasis, pathological stages and prognosis of NSCLC.

Strategies of digital fundus photography for screening diabetic retinopathy in a diabetic population in urban China.

PURPOSE: To evaluate the effect of mydriasis and different field strategies on technical failure, probability to refer diabetic retinopathy (DR, sensitivity) and probability not to refer patients without DR (specificity) of digital photography in screening with a fundus camera. METHODS: A total of 531 patients with diabetes underwent fundus photography with cross-combinations of mydriasis/nonmydriasis and single-field/two-field strategies, followed by slit lamp biomicroscopic examination by a trained ophthalmologist. Fundus photographs were graded independently by another experienced ophthalmologist. Calculations were first based on cases with non-gradable images treated as being referred and then with them excluded. RESULTS: Percentages of DR and referable DR in this patient cohort were 22.4% and 7.7%, respectively, based on slit lamp biomicroscopic examination. Mydriasis significantly reduced the technical failure rate from 27.1% to 8.3% under a single-field strategy, and from 28.2% to 8.9% under a two-field strategy. As compared to the single-field strategy, the two-field strategy increased sensitivity from 75.6% to 87.8% without mydriasis and from 73.2% to 90.2% with mydriasis. Mydriasis increased specificity from 68.8% to 84.3% in the single-field strategy and from 64.7% to 81.6% in the two-field strategy. Had the subjects with non-gradable images been excluded, the two-field strategy without mydriasis reported sensitivity of 85.7% and specificity of 91.6%. CONCLUSIONS: Both mydriasis and the two-field strategy are useful in photographic screening tests. Technical failure should be taken into consideration when screening strategies for DR are determined.

[An epidemiological study of visual disability and visual rehabilitation in Beijing].

OBJECTIVE: To investigate the status of visual disability and the demands for visual rehabilitation services in Beijing. METHODS: Five hundred and fifty-five persons with visual disability in Beijing from the Second National Survey on Disability of China were involved in this study. Their visual disability and demands for rehabilitation were evaluated. RESULTS: About three fourth of the visual disabled persons were over 60 years of age. Cataract, retinal and choroidal diseases, and glaucoma were the three leading causes of the visual impairment. Medical service was the number one (82.0%) demand for the persons with visual disability, although 89.4% of them had previously received some kinds of medial services. People who had received visual aid devices or rehabilitation training were 26.7% and 5.8%, respectively, while more people showed their demand for these service (36.6% and 11.9%, respectively). The demand for visual rehabilitation varied in different groups of age and severity of disability. CONCLUSION: Accessibility of high quality medical services for preventable blindness diseases should be further promoted. Public health education on visual rehabilitation is also needed.