The burden of knee osteoarthritis worldwide, regionally, and nationally from 1990 to 2019, along with an analysis of cross-national inequalities.

OBJECTIVE: To describe the disease burden of knee osteoarthritis (KOA) globally, regionally, and in 204 countries by age, sex, and sociodemographic index (SDI) from 1990 to 2019, and to explore cross-national inequalities across SDI. METHODS: The Global Burden of Disease (GBD) 2019 database collected data on KOA worldwide from 1990 to 2019, including prevalence, incidence, years lived with disability (YLDs). The average annual percentage change (AAPC) was used to measure temporal trends. In addition, the inequality slope index and the health concentration index were calculated to quantify the unequal distribution of the burden of KOA across 204 countries worldwide. RESULTS: In 2019, the global age-standardized prevalence rate increased by 7.5% compared with 1990, and the age-standardized incidence rate increased by about 6.2%; The age-standardized YLDs rate increased by about 7.8%. In addition to the Republic of Korea and the United States of America, the disease burden of KOA has increased year by year in other countries around the world. The incidence of KOA was highest at ages 50-59, while the prevalence and rates of YLDs were highest at ages 75-84. The burden of KOA was higher in women than in men. Cross-country inequality suggests that the inequality in the burden of KOA between high SDI and low SDI countries becomes greater, and that countries with high SDI bear a disproportionately high burden. CONCLUSION: The global KOA burden has risen steadily between 1990 and 2019, and cross-national inequality gaps remain large. Targeted measures must therefore be taken to address this inequality and the increasing global KOA disease burden.

The trends of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immunoinflammatory index in patients with intracerebral hemorrhage and clinical value in predicting pneumonia 30 days after surgery.

BACKGROUND: Inflammatory response is closely associated with secondary brain injury and pneumonia in intracerebral hemorrhage (ICH). In this study, we aimed to investigate the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immunoinflammatory index (SII) in the development of pneumonia in ICH patients 30 days after surgery. METHODS: We retrospectively collected clinical data on patients with ICH who underwent surgical treatment at our institution from January 2016 to December 2022, mainly including NLR, PLR and SII at different time points. Receiver operating characteristic (ROC) curves were used to compare the value of different inflammatory indicators in predicting the development of postoperative pneumonia 30 days after surgery in ICH patients, and multivariate logistic regression analyses were used to identify independent risk factors for pneumonia 30 days after surgery. RESULTS: Among 112 patients with intracerebral hemorrhage undergoing surgical treatment, 31 (27.7%) developed pneumonia postoperatively. The results of the univariate analysis demonstrated that patients in the pneumonia group experienced significantly higher blood glucose, NLR3, PLR3, and SII3 than those in the non- pneumonia group, and significantly lower admission Glasgow Coma Scale (GCS) scores than those in the Non- pneumonia group (all P<0.05). NLR, PLR, and SII showed an increasing and then decreasing in the disease process of intracerebral hemorrhage, and peaked at 48 hours postoperatively. Multivariable logistic regression analysis revealed that SII3 was an independent risk factor for postoperative pneumonia 30 days after surgery in ICH patients (OR=1.001, 95%CI: 1.000-1.002, P=0.008). The area under the curve (AUC) of the developed nomogram model was 0.895 (95%CI = 0.823 - 0.967), with a sensitivity and specificity of 0.903 and 0.815, respectively, providing good predictive power. CONCLUSIONS: In the course of intracerebral hemorrhage, NLR, PLR, and SII increased and then decreased, and peaked at 48 hours postoperatively. The SII3 was the best predictor of the occurrence of pneumonia postoperatively in ICH patients.

Burden of pancreatic cancer in older adults globally, regionally, and in 204 countries: 1990-2019 and projections to 2030.

BACKGROUND: Global aging is increasing; however, the epidemiologic characteristics of pancreatic cancer in older adults have not been systematically studied. METHODS: This study used data on pancreatic cancer in older adults from the Global Burden of Disease 2019 project. Temporal trends were measured using average annual percentage change and predicted using a Bayesian age-period-cohort model. In addition, the inequality slope index and the health concentration index scores were calculated to quantify the unequal distribution of the burden of pancreatic cancer in older adults. RESULTS: Between 1990 and 2019, the number of pancreatic cancer deaths in older adults, age-standardized death rate (ASDR), disability-adjusted life years (DALYs), and age-standardized DALY rate increased globally. In 2019, ASDR and age-standardized DALY rate for pancreatic cancer in older adults were the highest in Southern Latin America, whereas the burden has grown the fastest over the past 30 years in the Caribbean. The burden is predominantly distributed among those aged 65 to 74 years, with males having a higher burden than that of females. The global proportion of pancreatic cancer deaths in older adults attributed to smoking, high fasting plasma glucose, and high body mass index were 21.7%, 10.3%, and 5.8%, respectively. Both absolute and relative cross-national inequalities declined over the past 30 years but remained at medium-high levels of relative inequality. Deaths from pancreatic cancer among older adults are expected to continue to increase over the next 11 years. CONCLUSION: The global burden of pancreatic cancer among older adults has continued to rise over the past 30 years, and cross-national health inequalities remain high. Therefore, targeted measures must be taken to address this inequality.

Rational design of antibodies and development of a novel method for (1-3)-ß-D glucan detection as an alternative to Limulus amebocyte lysate assay.

With advances in medicine, increasing medical interventions have increased the risk of invasive fungal disease development. (1-3)-ß-D glucan (BDG) is a common fungal biomarker in serological tests. However, the scarcity of Limulus resources for BDG detection poses a challenge. This study addresses the need for an alternative to Limulus amebocyte lysate by using BDG mutant antibody for chemiluminescence detection. The wild-type BDG antibody was obtained by immunizing rabbits. An optimal V52HI/N34L Y mutant antibody, which has increased 3.7-fold of the testing efficiency compared to the wild-type antibody, was first achieved by mutating "hot-spot" residues that contribute to strong non-covalent bonds, as determined by alanine scanning and molecular dynamics simulation. The mutant was then applied to develop the magnetic particle chemiluminescence method. 574 clinical samples were tested using the developed method, with a cutoff value of 95 pg/mL set by Limulus amebocyte lysate. The receiver operating characteristic curve demonstrated an area under the curve of 0.905 (95% CI: 0.880-0.929). Chemiluminescence detected an antigen concentration of 89.98 pg/mL, exhibiting a sensitivity of 83.33% and specificity of 89.76%. In conclusion, the results showed a good agreement with Limulus amebocyte lysate and demonstrated the feasibility of using BDG mutant antibodies for invasive fungal disease diagnosis. The new method based on chemiluminescence for detecting BDG could shorten the sample-to-result time to approximately 30 min, rescue Limulus from being endangered and is resource efficient in terms of equipment and the non-use of a skilled technician.

Colorectal cancer and its attributable risk factors in East Asia, 1990-2030.

BACKGROUND: The disease burden of colorectal cancer in East Asia has been at a high level. However, the epidemiological characteristics of the disease burden in this region have not been systematically studied. METHOD: Data were obtained from the Global Burden of Disease 2019 program. Joinpoint analysis was used to identify long-term trends in mortality of colorectal cancer. Independent effects of age, period, and cohort were detected by the age-period-cohort model. The Bayesian age-period-cohort model was performed to predict the burden of colorectal cancer across East Asia by 2030. RESULTS: From 1990 to 2019, the average annual percentage change (AAPC) showed upward trends in mainland China (1.05 [95% confidence interval (CI)], 0.82, 1.28) as well as Taiwan Province of China (1.81 [95% CI], 1.51, 2.10) but downward in Japan (-0.60 [95% CI], -0.70, -0.49) (P < 0.05). Attributable risk factors for colorectal cancer in East Asia remained stable over 30 years, while the risk of metabolic factors is noteworthy in the future. In the next decade, the age-standardized death rate (ASDR) of colorectal cancer in China was predicted to surpass that of Japan and South Korea in expectation. CONCLUSION: The mortality of colorectal cancer is escalating in developing countries, while it is gradually declining in high-income countries across East Asia. Nonetheless, the disease burden of colorectal cancer in high-income countries remains substantial level.

Scoparone from Artemisia capillaris Thunb. induces apoptosis in HepG2 cells via activation of both intracellular and extracellular pathways.

Six separated compounds were identified from Artemisia capillaris Thunb., and they were 7-methoxycoumarin (1), 6,7-dimethoxycoumarin (2), 7-hydroxy-6-methoxycoumarin (3), quercetin (4), chlorogenic acid (5) and caffeic acid (6). Among them, 6,7-dimethoxycoumarin, as known as scoparone, was the most effective on scavenging ABTS free radicals (IC50 = 0.97 µΜ) and was then tested by cytotoxic activity and pro-apoptotic activity against HepG2 cells. Scoparone dose-dependently and time-dependently inhibited the cell proliferation. Furthermore, scoparone induced the expression of Bax, concurrently suppressing the expression of Bcl-2, resulting in a noteworthy elevation in the Bax/Bcl-2 ratio to up-regulate Caspase-3 activity, thus inducing cell apoptosis via the intracellular pathway. Meanwhile, scoparone promoted the expression of Fas, FasL, FADD, Caspase-8 and Caspase-3, indicating that scoparone also triggered apoptosis via the extracellular pathway. In a word, scoparone demonstrated remarkable antitumor capability to induce apoptosis of HepG2 cells through both intracellular and extracellular pathways.

Global, regional, and national burden of liver cancer due to non-alcoholic steatohepatitis, 1990-2019: a decomposition and age-period-cohort analysis.

BACKGROUND: Identifying past temporal trends in non-alcoholic steatohepatitis (NASH)-associated liver cancer (NALC) can increase public awareness of the disease and facilitate future policy development. METHODS: Annual deaths and age-standardized death rates (ASDR) for NALC from 1990 to 2019 were collected from the Global Burden of Disease (GBD) 2019 study. The long-term trend and the critical inflection of mortality of NALC were detected by Joinpoint analysis. Age-period-cohort analysis was employed to evaluate the effects of age, period, and cohort. Last, decomposition analysis was used to reveal the aging and population growth effects for NALC burden. RESULTS: Between 1990 and 2019, the ASDR of NALC witnessed an overall declining trend on a global scale, with a decrease in females and a stable trend in males. However, the global ASDR demonstrated a significant upward trend from 2010 to 2019. Southern sub-Saharan Africa and Southeast Asia have the highest NALC burdens, while high socio-demographic index (SDI) region experienced the fastest escalation of NALC burdens over 30 years. The decomposition analysis revealed that population growth and aging were the primary catalysts behind the increase in global NALC deaths. Age-period-cohort analyses showed that NALC mortality declined the fastest among females aged 40-45 years in high SDI region, accompanied by a deteriorating period effect trend during the period of 2010-2019. CONCLUSION: The global absolute deaths and ASDR of NALC have witnessed a rise in the past decade, with populations exhibiting considerable disparities based on sex, age, and region. Population growth, aging, and metabolism-related factors were the main factors behind the increase in global NALC deaths.

Pancreatic Cancer and its Attributable Risk Factors in East Asia, Now and Future.

BACKGROUND: The disease burden of pancreatic cancer in East Asia is at a high level, but the epidemiological characteristics of pancreatic cancer in the region have not been systematically studied. METHOD: Joinpoint analysis was used to identify average annual percentage change (AAPC) and annual percentage change (APC) in mortality. Age-period-cohort models were used to analyze age-period cohort effects across countries. Bayesian age-period-cohort (BAPC) analysis was used to project the burden of disease for 2020-2030. RESULTS: Pancreatic cancer mortality in males in Japan (2012-2019, APC = -0.97) and Korea (2012-2019, APC = -0.91) has shown a decreasing trend since 2012 (P < .05). However, China (2016-2019, APC = 3.21), Mongolia (2015-2.019, APC = 2.37), and North Korea (2012-2019, APC = 0.47) showed a significant increase in pancreatic cancer in both genders (P < .05). Risk factors for pancreatic cancer in East Asia remained largely stable between 2010 and 2019. Mortality of pancreatic cancer due to smoking began to decline in areas with high socio-demographic index (SDI), and mortality of pancreatic cancer due to high body mass index and high fasting plasma glucose increased with SDI. The age-standardized mortality for pancreatic cancer in Chinese males is expected to exceed that of Japan and South Korea by 2030, but the disease burden of pancreatic cancer in Japan and South Korea remains at extremely high levels. CONCLUSION: Economically developed countries are beginning to show a decreasing trend in the burden of pancreatic cancer disease, and developing countries are experiencing a rapid increase in the age-standardized death rate (ASDR) of pancreatic cancer.

The trend of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in spontaneous intracerebral hemorrhage and the predictive value of short-term postoperative prognosis in patients.

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) play an important role in the inflammatory response in various diseases, but the role in the course of spontaneous intracerebral hemorrhage (ICH) is unclear. Methods: This study retrospectively collected baseline characteristics and laboratory findings, including NLR and PLR at different time points, from spontaneous ICH patients undergoing surgery between January 2016 and June 2021. Patients were scored using the modified Rankin Scale (mRS) to evaluate their functional status at 30 days post-operation. Patients with mRS score ≥3 were defined as poor functional status, and mRS score <3 was defined as good functional status. The NLR and PLR were calculated at admission, 48 h after surgery and 3-7 days after surgery, respectively, and their trends were observed by connecting the NLR and PLR at different time points. Multivariate logistic regression analysis was used to identify independent risk factors affecting the prognosis of ICH patients at 30 days after surgery. Results: A total of 101 patients were included in this study, and 59 patients had a poor outcome at 30 days after surgery. NLR and PLR gradually increased and then decreased, peaking at 48 h after surgery. Univariate analysis demonstrated that admission Glasgow Coma Scale (GCS) score, interval from onset to admission, hematoma location, NLR within 48 h after surgery and PLR within 48 h after surgery were associated with poor 30-day prognosis. In multivariate logistic regression analysis, NLR within 48 h after surgery (OR, 1.147; 95% CI, 1.005, 1.308; P, 0.042) was an independent risk factor for 30-day after surgery prognosis in spontaneous ICH patients. Conclusion: In the course of spontaneous intracerebral hemorrhage, NLR and PLR initially increased and subsequently decreased, reaching their peak values at 48 h after surgery. High NLR within 48 h after surgery was an independent risk factor for poor prognosis 30 days after surgery in spontaneous ICH patients.

Inflammatory bowel diseases, interleukin-6 and interleukin-6 receptor subunit alpha in causal association with cerebral cortical structure: a Mendelian randomization analysis.

Background: Neurological involvement and psychiatric manifestations have been documented in clinical cases of inflammatory bowel disease (IBD); however, the presence of a causal relationship remains elusive. The objective of this study is to investigate the modifications occurring in the cerebral cortex as a result of IBD. Methods: A compendium of data extracted from a genome-wide association study (GWAS) involving a maximum of 133,380 European subjects. A series of Mendelian random analyses were applied to exclude heterogeneity and pleiotropy, ensuring the stability of the results. Results: Neither IBDs nor inflammatory cytokines (IL-6/IL-6Rα) were found to have a significant causality with surface area (SA) and thickness (TH) at the global level. At the regional functional brain level, Crohn's disease (CD) significantly decreased the TH of pars orbitalis (ß=-0.003mm, Se=0.001mm, pivw =4.85×10-4). IL-6 was observed to reduce the SA of middle temporal (ß=-28.575mm2, Se=6.482mm2, pivw=1.04×10-5) and increase the TH of fusiform (ß=0.008mm, Se=0.002mm, pivw=8.86×10-5) and pars opercularis (ß=0.009mm, Se=0.002mm, pivw=2.34×10-4). Furthermore, a causal relationship between IL-6Rα and an increase in the SA of superior frontal (ß=21.132mm2, Se=5.806mm2, pivw=2.73×10-4) and the TH of supramarginal (ß=0.003mm, Se=0.0002mm, pivw=7.86×10-37). All results passed sensitivity analysis and no heterogeneity and pleiotropy were detected. Conclusion: The correlation between IBD and changes in cerebral cortical structures implies the existence of a gut-brain axis at the organismal level. It is recommended that clinical patients with IBD prioritize long-term management of inflammation, as changes at the organismal level can lead to functional pathologies. Magnetic resonance imaging (MRI) may be considered as an additional screening option for IBD.

Exercise for Neuropathic Pain: A Systematic Review and Expert Consensus.

Background: Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases. The study aimed to summarize the effectiveness and efficacy of exercise for various diseases with NP supported by evidence, describe expert recommendations for NP from different causes, and inform policymakers of the guidelines. Design: A systematic review and expert consensus. Methods: A systematic search was conducted in PubMed. We included systematic review and meta-analysis, randomized controlled trials (RCTs), which assessed patients with NP. Studies involved exercise intervention and outcome included pain intensity at least. Physiotherapy Evidence Database and the Assessment of Multiple Systematic reviews tool were used to grade the quality assessment of the included RCTs and systematic reviews, respectively. The final grades of recommendation were based on strength of evidence and a consensus discussion of results of Delphi rounds by the Delphi consensus panel including 21 experts from the Chinese Association of Rehabilitation Medicine. Results: Eight systematic reviews and 21 RCTs fulfilled all of the inclusion criteria and were included, which were used to create the 10 evidence-based consensus statements. The 10 expert recommendations regarding exercise for NP symptoms were relevant to the following 10 different diseases: spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, cervical radiculopathy, sciatica, diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV/AIDS, and surgery, respectively. The exercise recommended in the expert consensus involved but was not limited to muscle stretching, strengthening/resistance exercise, aerobic exercise, motor control/stabilization training and mind-body exercise (Tai Chi and yoga). Conclusions: Based on the available evidence, exercise is helpful to alleviate NP intensity. Therefore, these expert consensuses recommend that proper exercise programs can be considered as an effective alternative treatment or complementary therapy for most patients with NP. The expert consensus provided medical staff and policymakers with applicable recommendations for the formulation of exercise prescription for NP. This consensus statement will require regular updates after five-ten years.

Circulating tumor cell count and serum CEA mRNA level predict postoperative recurrence of digestive tract cancer.

OBJECTIVE: To evaluate the predictive value of circulating tumor cell count (CTC) and serum carcinoembryonic antigen (CEA) mRNA levels in postoperative recurrence of digestive tract cancer. METHODS: A total of 52 patients with digestive tract cancer who underwent radical resection in our hospital were divided into a recurrent group (n=18) and a non-recurrent group (n=34). The CTC and CEA mRNA levels of the two groups were compared one day before the operation. Pearson correlation analysis was used to analyze the correlation between CTC and CEA mRNA levels. The curve of subjects' working characteristics was used to analyze the predictive value of the serum CTC and the level of CEA mRNA in postoperative recurrence of digestive tract cancer. The correlation of CTC and CEA mRNA expression with different age, sex, cancer type and TNM stage was further analyzed. RESULTS: CTC and CEA mRNA levels in the recurrent group were higher than those in the non-recurrent group (P<0.05). CTC was positively correlated with the CEA mRNA level by Pearson correlation (r=0.609, P=0.000). ROC curve showed that the area under the curve of CEA mRNA, CTC and combined test in predicting postoperative recurrence of digestive tract cancer were 0.912, 0.831 and 0.965 respectively. The area under the curve of the combined test and CEA mRNA level was significantly higher than that of CTC (Z=3.794, P=0.000; Z=2.001, P=0.045). There was no significant difference in the area under the curve between combined detection and CEA mRNA (Z=1.437 and P=0.151). There was no significant difference in CTC and CEA mRNA levels among patients with different sex, age, body weight, differentiation degree and histological type (P>0.05). The CTC and CEA mRNA levels of patients in stage lll and lV were higher than those in stage l and ll and the difference was statistically significant (P<0.05). By Spearman rank correlation analysis, it was found that CTC and CEA mRNA levels were positively correlated with the TNM stage (r=0.532, 0.712, P<0.05). CONCLUSION: levels of CTC and serum CEA mRNA have a certain value in predicting postoperative recurrence of digestive tract cancer and their expression is closely related to TNM stage. Clinical diagnosis of both of them can improve the diagnostic efficiency of predicting postoperative recurrence.

[Effect of directive differentiation of microglia by SN50 on hypoxia-caused neurons injury in mice].

OBJECTIVE: To explore the effect and mechanism of directive differentiation of microglia by SN50 on hypoxia-caused neurons injury in mice. METHODS: The microglia were isolated and purified from brain tissue of new-born BALB/c mice through differential velocity adherent and vibration technique. The quantity of the microglia was identified by immunofluorescence staining of inducible nitric oxide synthetase (iNOS) and ionized calcium binding adapter molecule 1 (Iba1) and real-time fluorescence quantitative PCR (qRT-PCR) for special expression genes [iNOS, CD32, and interlenkin 10 (IL-10)]. Then the microglia were cultured with SN50, and the expressions of nuclear factor κB (NF-κB), differentiation-related genes (iNOS, CD11b, IL-10, and CD206), and apoptosis were detected by Western blot, qRT-PCR, and flow cytometry, respectively. The hypoxia model of neuron was established, and the cell apoptosis was evaluated by MTT after 0, 2, 6, 12, 24, and 48 hours of anoxic treatment. The apoptosis related markers (Bcl-2 and Caspase-3) were measured by Western blot and flow cytometry. In addition, the neurons after anoxic treatment were co-cultured with SN50 treated microglia (experimental group) and normal microglia (control group) for 24 hours. And the cell viability and apoptosis related markers (Bcl-2 and Caspase-3) were also measured. RESULTS: Immunofluorescence staining and qRT-PCR analysis showed that the cells expressed the specific proteins and genes of microglia. Compared with the normal microglia, the relative expressions of NF-κB protein and iNOS and CD11b mRNAs in the microglia treated with SN50 significantly decreased ( P<0.05), the relative expressions of IL-10 and CD206 mRNAs significantly increased ( P<0.05), and the cell apoptosis rate had no significant change ( P>0.05). Compared with the normal neurons, the cell viability, the relative expressions of Bcl-2 and Caspase-3 proteins after anoxic treatment significantly decreased ( P<0.05), while the relative expressions of cleaved-Caspase-3 protein and cell apoptosis rate of neurons significantly increased ( P<0.05). In the co-culture system, the cell viability, the relative expressions of Bcl-2 and Caspase-3 proteins were significantly higher in experimental group than those in control group ( P<0.05), while the relative expressions of cleaved-Caspase-3 protein and cell apoptosis rate were significantly lower in experimental group than those in control group ( P<0.05). CONCLUSION: SN50 can induce the microglia differentiation into M2 type through NF-κB pathway. The SN50-induced microglia can protect neurons from hypoxic injury.

Preventive Cold Acclimation Augments the Reparative Function of Endothelial Progenitor Cells in Mice.

BACKGROUND/AIMS: Chronic cold exposure may increase energy expenditure and contribute to counteracting obesity, an important risk factor for cerebrocardiovascular diseases. This study sought to evaluate whether preventive cold acclimation before ischemia onset might be a promising option for preventing cerebral ischemic injury. METHODS: After a 14-day cold acclimation period, young and aged mice were subjected to permanent cerebral ischemia, and histological analyses and behavioral tests were performed. Mouse endothelial progenitor cells (EPCs) were isolated, their function and number were determined, and the effects of EPC transplantation on cerebral ischemic injury were investigated. RESULTS: Preventive cold acclimation before ischemia onset increased EPC function, promoted ischemic brain angiogenesis, protected against cerebral ischemic injury, and improved long-term stroke outcomes in young mice. In addition, transplanted EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic injury and promote local angiogenesis compared to those from control mice, and EPCs from donor animals could integrate into the recipient ischemic murine brain. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury, which could be improved by preventive cold acclimation. Moreover, preventive cold acclimation could also enhance EPC function, promote local angiogenesis, and protect against cerebral ischemic injury in aged mice. CONCLUSIONS: Preventive cold acclimation before ischemia onset improved long-term stroke outcomes in mice at least in part via promoting the reparative function of EPC. Our findings imply that a variable indoor environment with frequent cold exposure might benefit individuals at high risk for stroke.

Investigating genetic characteristics of hepatitis B virus-associated and -non-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver malignancy that mainly occurs in patients with chronic liver disease and cirrhosis. Risk factors for HCC include hepatitis B virus (HBV) infection. However, the specific role of HBV infection in HCC development is not yet completely understood. In order to reveal the effects of HBV on HCC, we compare the genes of HCC patients infected with HBV with those who are not infected. METHODS: We encoded the genes of these two types of HCC in databases using enrichment scores of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway terms. A random forest algorithm was employed in order to distinguish these two types in the classifier, and a series of feature selection approaches was used in order to select their optimal features. Novel HBV-associated and -non-associated HCC genes were predicted, respectively, based on their optimal features in the classifier. A shortest-path algorithm was also employed in order to find all of the shortest-paths genes connecting the known related genes. RESULTS: A total of 54 different features between HBV-associated and -non-associated HCC genes were identified. In total, 1236 and 881 novel related genes were predicted for HBV-associated and -non-associated HCC, respectively. By integrating the predicted genes and shortest path genes in their gene interaction network, we identified 679 common genes involved in the two types of HCC. CONCLUSION: We identified the significantly different genetic features between two types of HCC. We also predicted related genes for the two types based on their specific features. Finally, we determined the common genes and features that were involved in both of these two types of HCC.

The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss.

Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application.

[PROXIMAL FIBULAR OSTEOTOMY COMBINED WITH ARTHROSCOPIC DEBRIDEMENT FOR TREATING MEDIAL KNEE OSTEOARTHRITIS WITH VARUS].

OBJECTIVE: To evaluate the effectiveness of proximal fibular osteotomy combined with arthroscopic debridement in the treatment of medial knee osteoarthritis with varus. METHODS: Between December 2013 and June 2015, 61 patients with medial knee osteoarthritis with varus were treated by arthroscopic debridment in 32 cases (group A) and by proximal fibular osteotomy combined with arthroscopic debridement in 29 cases (group B). No significant difference was found in gender, age, side, disease duration, OA stage, visual analogue scale (VAS) score, and knee society score (KSS) between 2 groups (P>0.05). The clinical outcome was evaluated by VAS score and KSS score at 1 week, 3 months, and 12 months after operation. RESULTS: The patients in 2 groups were followed up 12 months. All incisions healed by first intention. There was no significant difference in complication incidence between groups A and B (0 vs. 3.4%; χ2=0.723, P=0.432). The VAS scores were significantly decreased at 1 week, 3 months, and 12 months after operation when compared with preoperative score in 2 groups (P<0.05). The VAS score of group A was significantly lower than that of group B at 1 week after operation (P<0.05), but the VAS score of group A was significantly higher than that of group B at 3 months, and 12 months after operation (P<0.05). The knee function was obviously improved in 2 groups, and the KSS scores at 1 week, 3 months and 12 months after operation were significantly better than preoperative score (P<0.05). The KSS score of group A was significantly lower than that of group B at 3 months, and 12 months after operation (P<0.05). CONCLUSIONS: Proximal fibular osteotomy combined with arthroscopic debridement can treat knee malalignment and disease in knee, it is an effective and safe method to treat the medial knee osteoarthritis with varus.

RNAi Silencing of IL-1ß and TNF-α in the Treatment of Post-traumatic Arthritis in Rabbits.

Post-traumatic arthritis is a secondary complication to severe joint trauma. With the disease progression, it may eventually lead to osteoarthritis in patients whose age is considerably younger than patients with traditional bone arthritis. The main objective of this study was to explore the feasibility of using lentiviral-mediated RNA interference silencing of IL-1ß and TNF-α to treat post-traumatic arthritis in rabbits. About 48 New Zealand rabbits underwent bilateral knee joint surgery to stimulate traumatic arthritis. They were then randomly divided into four groups of 12 rabbits each. The histopathology of the cartilage was observed, and the changes were assessed by Mankin scoring. ELISA was used to detect the expression of IL-1ß and TNF-α in the synovial fluid. (i) Compared with the control group, the transfection and co-transfected groups displayed reduced cartilage damage and speed of degeneration. The co-transfected group showed the greatest alleviation of symptoms. The Mankin score was statistically different (p < 0.01). (ii) Compared with the control group, the expression of IL-1ß or TNF-α was reduced in the respective transfection groups (p < 0.01 in both groups) and IL-1ß and TNF-α were reduced in the co-transfected group (p < 0.01). The co-transfected group showed the lowest expression of the three experimental groups of both IL-1ß and TNF-α (p < 0.01). Lentivirus-mediated RNA interference can knock down the expression of IL-1ß and TNF-α in joint fluids and, in a synergistic effect when two siRNAs are co-transfected, ease cartilage degeneration.