Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study.

PURPOSE: Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases. PATIENTS AND METHODS: Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis. RESULTS: Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-ß, 1.099 [95%CI, 1.037-1.166], P = 0.002; SCF, 1.155 [95%CI, 1.015-1.315], P = 0.029; MCP-1, 1.103 [95%CI, 1.012-1.202], P = 0.026; IL-10, 1.102 [95%CI, 1.012-1.200], P = 0.025; eotaxin, 1.086 [95%CI, 1.002-1.176], P = 0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894-0.999], P = 0.047; IL1ra, 0.886 [95%CI, 0.809-0.969], P = 0.008; IL-1ß, 0.866 [95%CI, 0.762-0.983], P = 0.027; IL-9, 0.908 [95%CI, 0.841-0.980], P = 0.014; IL2ra, 1.065 [95%CI, 1.004-1.130], P = 0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009-1.077], P = 0.011; IL-16, 1.032 [95%CI, 1.001-1.064], P = 0.046; IL1ra, 0.942 [95%CI, 0.887-0.999], P = 0.047; FGF-basic, 1.144 [95%CI, 1.052-1.244], P = 0.002). Furthermore, sensitivity analysis results supported the above associations. CONCLUSION: This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.

Correlation between the triglyceride-glucose index and arterial stiffness in Japanese individuals with normoglycaemia: a cross-sectional study.

BACKGROUND: The association between the triglyceride-glucose (TyG) index and arterial stiffness in individuals with normoglycaemia remains unclear. We aimed to evaluate the relationship between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia, providing additional evidence for predicting early arterial stiffness. METHODS: This study included 15,453 adults who participated in the NAGALA Physical Examination Project of the Murakami Memorial Hospital in Gifu, Japan, from 2004 to 2015. Data on clinical demographic characteristics and serum biomarker levels were collected. The TyG index was calculated from the logarithmic transformation of fasting triglycerides multiplied by fasting glucose, and arterial stiffness was measured using the estimated pulse wave velocity calculated based on age and mean blood pressure. The association between the TyG index and arterial stiffness was analysed using a logistic regression model. RESULTS: The prevalence of arterial stiffness was 3.2% (500/15,453). After adjusting for all covariates, the TyG index was positively associated with arterial stiffness as a continuous variable (adjusted odds ratio (OR) = 1.86; 95% Confidence Interval = 1.45-2.39; P<0.001). Using the quartile as the cutoff point, a regression analysis was performed for arterial stiffness when the TyG index was converted into a categorical variable. After adjusting for all covariates, the OR showed an upward trend; the trend test was P<0.001. Subgroup analysis revealed a positive association between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia and different characteristics. CONCLUSION: The TyG index in Japanese individuals with normoglycaemia is significantly correlated with arterial stiffness, and the TyG index may be a predictor of early arterial stiffness.

SpoT-mediated NapA upregulation promotes oxidative stress-induced Helicobacter pylori biofilm formation and confers multidrug resistance.

Recently, there is increased incidence of drug-resistant Helicobacter pylori infection. Biofilm formation confers multidrug resistance to bacteria. Moreover, it has been found that the formation of biofilm on the surface of gastric mucosa is an important reason for the difficulty of eradication of H. pylori The mechanisms underlying H. pylori biofilm formation in vivo have not been elucidated. Reactive oxygen species (ROS) released by the host immune cells in response to H. pylori infection cannot effectively clear the pathogen. Moreover, the extracellular matrix of the biofilm protects the bacteria against ROS-mediated toxicity. This study hypothesized that ROS can promote H. pylori biofilm formation and treatment with low concentrations of hydrogen peroxide (H2O2) promoted this process in vitro The comparative transcriptome analysis of planktonic and biofilm-forming cells revealed that the expression of SpoT, a (p)ppGpp (guanosine 3'-diphosphate 5'-triphosphate and guanosine 3',5'-bispyrophosphate) synthetase/hydrolase, is upregulated in H2O2-induced biofilms and that knockout of spoT inhibited H. pylori biofilm formation. Additionally, this study examined the key target molecules involved in SpoT regulation using weighted gene co-expression network analysis. The analysis revealed that neutrophil-activating protein (NapA; HP0243) promoted H2O2-induced biofilm formation and conferred multidrug resistance. Furthermore, vitamin C exhibited anti-H. pylori biofilm activity and downregulated the expression of napA in vitro These findings provide novel insight into the clearance of H. pylori biofilms.

Association between relative muscle strength and hypertension in middle-aged and older Chinese adults.

BACKGROUND: The association between muscle defects and hypertension is well-established. However, the absence of pertinent and uncomplicated clinical indicators presents a challenge. Relative muscle strength (RMS) may offer a viable indicator. This study aimed to explore the association between RMS and hypertension. METHODS: A total of 12,720 individuals aged ≥ 45 years from the 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) were included. Grip strength was recorded and appendicular skeletal muscle mass (ASM) was estimated using a validated mathematical formula. The RMS was calculated as the ratio of grip strength to ASM. Hypertension was determined based on previous diagnosis, history of hypertension medication use, and current blood pressure. Logistic regression models were employed to investigate the relationship between RMS and hypertension. RESULTS: The prevalence of hypertension was 41.7% (5,307/12,720 patients). RMS was negatively correlated with hypertension with an OR (95% CI) of 0.68 (0.59-0.79) for males, 0.81 (0.73-0.90) for females, and 0.78 (0.72-0.85) for the entire population after adjusting for related covariates including age, education, marital history, smoking history, drinking history, diabetes, hyperlipidemia, and obesity. The trend test showed a linear association among males, females, or the entire population. Stratified analysis showed a consistent negative correlation between RMS and hypertension. CONCLUSIONS: Higher RMS is an independent protective factor against hypertension and efforts to promote RMS may be beneficial for the prevention and management of hypertension.

Comparison between spleen and liver stiffness measurements by sound touch elastography for diagnosing cirrhosis at different aminotransferase levels: a prospective multicenter study.

OBJECTIVES: To compare the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by sound touch elastography (STE) for the diagnosis of cirrhosis at different alanine aminotransferase (ALT) levels, and to compare the applicability and repeatability of SSM with LSM performed by STE, a new two-dimensional shear wave elastography technology. METHODS: This prospective multicenter study included 25 centers and recruited chronic hepatitis B (CHB) patients with liver biopsy between May 2018 and November 2019. All patients underwent LSM and SSM by STE. Success and reliability rates were calculated and compared. Intra-observer agreement was assessed using intraclass correlation coefficients (ICCs). Differences between areas under the receiver operating characteristic curves (AUCs) of LSMs and SSMs at different ALT levels were compared using the Delong test. RESULTS: Among 603 CHB patients, the success and reliability rates of SSM were 94.53% (570/603) and 85.74% (517/603), respectively, which were similar to those of LSM (p > 0.05), respectively. The ICC for intra-observer agreements of SSM was 0.964 (p < 0.001). In the total cohort, ALT ≤ 2 × upper limit of normal (ULN) group, and A0-1 group, the AUCs of SSMs were significantly lower than those of LSMs for the diagnosis of cirrhosis (p < 0.001). In the ALT > 2 × ULN group and A2-3 group, the AUC of SSM improved and was not significantly different from that of LSM (p = 0.342, p = 0.510, respectively). CONCLUSIONS: SSM by STE achieved applicability and repeatability equivalent to those of LSM. SSM might be a good substitute to LSM in patients with high ALT levels. KEY POINTS: • Spleen stiffness measurement performed by sound touch elastography was proven to have similar applicability and repeatability to liver stiffness measurement in this prospective multicenter study. • Spleen stiffness measurement demonstrated a poorer diagnostic performance for cirrhosis compared with liver stiffness measurement in the total cohort and low ALT level group, yet it showed a similar diagnostic performance to liver stiffness measurement in patients with high ALT levels.

Prevalence of dry eye disease among Chinese high school students during the COVID-19 outbreak.

PURPOSE: The study aimed to investigate the prevalence of dry eye disease (DED) and relevant risk factors among Chinese high school students during the COVID-19 outbreak. METHODS: A cross-sectional study was conducted from November to December 2020, and 4825 high school students from nine high schools in Shanghai were recruited. All students completed ocular surface disease index (OSDI) and perceived stress scale (PSS) questionnaires and answered other questions designed to ascertain information on the risk factors related to DED. DED was diagnosed when OSDI scores were greater than or equal to 13. The prevalence of symptomatic DED was determined. A T-test, Kruskal-Wallis test, Chi-square test, and logistic regression analysis were used to examine the possible risk factors. RESULTS: The prevalence of symptomatic DED among Chinese high school students was 70.5%. In univariate analysis, higher PSS scores (P<0.001), prolonged video display terminal (VDT) use (P<0.001), wearing contact lenses (P=0.001), poor sleep quality (P<0.001), and being female (P<0.001) were significantly correlated with dry eyes. In multivariate logistic regression analysis, higher PSS scores (P<0.001, OR=1.20), prolonged VDT use (P<0.001, OR=1.07), poor sleep quality (P<0.001, OR=1.84), and being female (P=0.001, OR=1.25) were significant risk factors associated with DED. CONCLUSIONS: Due to the epidemic, most Chinese high school students are in a high-risk environment in which they are more likely to suffer from DED, such as long online courses and heavy stress from school. Relevant preventive measures that may have a positive impact on public health and quality of life for high school students should be brought to the forefront.

Transporters HP0939, HP0497, and HP0471 participate in intrinsic multidrug resistance and biofilm formation in Helicobacter pylori by enhancing drug efflux.

BACKGROUND: The multidrug resistance of Helicobacter pylori is becoming an increasingly serious issue. It is therefore necessary to study the mechanism of multidrug resistance of H pylori. We have previously identified that the HP0939, HP0497, and HP0471 transporters affect the efflux of drugs from H pylori. As efflux pumps participate in bacterial multidrug resistance and biofilm formation, we hypothesized that these transporters could be involved in the multidrug resistance and biofilm formation of H pylori. MATERIALS AND METHODS: We therefore constructed three knockout strains, Δhp0939, Δhp0497, and Δhp0471, and three high-expression strains, Hp0939he , Hp0497he , and Hp0471he , using the wild-type (WT) 26 695 strain of H pylori as the template. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of wild strains, knockout strains, and high-expression strains to amoxicillin, metronidazole, and other antibiotics were measured. The efflux capacity of high-expression strains and wild strains was compared by Hoechst 33 342 accumulation assay. RESULTS: Determination of the MIC and MBC of the antibiotics revealed that the knockout strains were more sensitive to antibiotics, while the high-expression strains were less sensitive to antibiotics, compared to the WT. The ability of the high-expression strains to efflux drugs was significantly higher than that of the WT. We also induced H pylori to form biofilms, and observed that the knockout strains could barely form biofilms and were more sensitive to several antibiotics, compared to the WT. The mRNA expression of hp0939, hp0497, and hp0471 in the clinically sensitive and multidrug-resistant strains was determined, and it was found that these genes were highly expressed in the multidrug-resistant strains that were isolated from the clinics. CONCLUSIONS: In this study, we found three transporters involved in intrinsic multidrug resistance of H pylori.

Bifunctional Enzyme SpoT Is Involved in Biofilm Formation of Helicobacter pylori with Multidrug Resistance by Upregulating Efflux Pump Hp1174 (gluP).

The drug resistance of Helicobacter pylori is gradually becoming a serious problem. Biofilm formation is an important factor that leads to multidrug resistance (MDR) in bacteria. The ability of H. pylori to form biofilms on the gastric mucosa is known. However, there are few studies on the regulatory mechanisms of H. pylori biofilm formation and multidrug resistance. Guanosine 3'-diphosphate 5'-triphosphate and guanosine 3',5'-bispyrophosphate [(p)ppGpp] are global regulatory factors and are synthesized in H. pylori by the bifunctional enzyme SpoT. It has been reported that (p)ppGpp is involved in the biofilm formation and multidrug resistance of various bacteria. In this study, we found that SpoT also plays an important role in H. pylori biofilm formation and multidrug resistance. Therefore, it was necessary to carry out some further studies regarding its regulatory mechanism. Considering that efflux pumps are of great importance in the biofilm formation and multidrug resistance of bacteria, we tried to determine whether efflux pumps controlled by SpoT participate in these activities. We found that Hp1174 (glucose/galactose transporter [gluP]), an efflux pump of the major facilitator superfamily (MFS), is highly expressed in biofilm-forming and multidrug-resistant (MDR) H. pylori strains and is upregulated by SpoT. Through further research, we determined that gluP is involved in H. pylori biofilm formation and multidrug resistance. Furthermore, the average expression level of gluP in the clinical MDR strains (C-MDR) was considerably higher than that in the clinical drug-sensitive strains (C-DSS). Taken together, our results revealed a novel molecular mechanism of H. pylori resistance to multidrug exposure.

Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial.

BACKGROUND: Acupuncture has been used for chronic constipation, but evidence for its effectiveness remains scarce. OBJECTIVE: To determine the efficacy of electroacupuncture (EA) for chronic severe functional constipation (CSFC). DESIGN: Randomized, parallel, sham-controlled trial. (ClinicalTrials.gov: NCT01726504). SETTING: 15 hospitals in China. PARTICIPANTS: Patients with CSFC and no serious underlying pathologic cause for constipation. INTERVENTION: 28 sessions of EA at traditional acupoints or sham EA (SA) at nonacupoints over 8 weeks. MEASUREMENTS: The primary outcome was the change from baseline in mean weekly complete spontaneous bowel movements (CSBMs) during weeks 1 to 8. Participants were followed until week 20. RESULTS: 1075 patients (536 and 539 in the EA and SA groups, respectively) were enrolled. The increase from baseline in mean weekly CSBMs during weeks 1 to 8 was 1.76 (95% CI, 1.61 to 1.89) in the EA group and 0.87 (CI, 0.73 to 0.97) in the SA group (between-group difference, 0.90 [CI, 0.74 to 1.10]; P < 0.001). The change from baseline in mean weekly CSBMs during weeks 9 to 20 was 1.96 (CI, 1.78 to 2.11) in the EA group and 0.89 (CI, 0.69 to 0.95) in the SA group (between-group difference, 1.09 [CI, 0.94 to 1.31]; P < 0.001). The proportion of patients having 3 or more mean weekly CSBMs in the EA group was 31.3% and 37.7% over the treatment and follow-up periods, respectively, compared with 12.1% and 14.1% in the SA group (P < 0.001). Acupuncture-related adverse events during treatment were infrequent in both groups, and all were mild or transient. LIMITATIONS: Longer-term follow-up was not assessed. Acupuncturists could not be blinded. CONCLUSION: Eight weeks of EA increases CSBMs and is safe for the treatment of CSFC. Additional study is warranted to evaluate a longer-term treatment and follow-up. PRIMARY FUNDING SOURCE: Ministry of Science and Technology of the People's Republic of China through the Twelfth Five-Year National Science and Technology Pillar Program.

A Two-Decade Bibliometric Analysis of Laser in Ophthalmology: From Past to Present.

Background: Laser therapy has been proven as an effective technique for managing ophthalmological disorders. To guide future research, we conducted a bibliometric analysis of laser applications in eye diseases from 1990 to 2022, aiming to identify key themes and trends. Methods: We retrieved 3027 publications from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks. Results: From a co-citation reference network, we identified 52 distinct clusters. Our analysis uncovered three main research trends. The first trend revolves around the potential evolution of corneal laser surgery techniques, shifting from the treatment of refractive errors to broader applications in biomedical optics. The second trend illustrates the advancement of laser applications in treating a range of disorders, from retinal and ocular surface diseases to glaucoma. The third trend focuses on the innovative uses of established technologies. Conclusion: This study offers significant insights into the evolution of laser applications in ophthalmology over the past 30 years, which will undoubtedly assist scientists in directing further research in this promising field.

Genetic correlation between circulating metabolites and chalazion: a two-sample Mendelian randomization study.

Background: Lipid metabolism disorders were observationally associated with chalazion, but the causality of the related circulating metabolites on chalazion remained unknown. Here, we investigated the potential causal relationship between circulating metabolites and chalazion using two-sample Mendelian randomization (MR) analysis. Methods: For the primary analysis, 249 metabolic biomarkers were obtained from the UK Biobank, and 123 circulating metabolites were obtained from the publication by Kuttunen et al. for the secondary analysis. Chalazion summary data were obtained from the FinnGen database. Inverse variance weighted (IVW) is the main MR analysis method, and the MR assumptions were evaluated in sensitivity and colocalization analyses. Results: Two MR analyses results showed that the common metabolite, alanine, exhibited a genetic protective effect against chalazion (primary analysis: odds ratio [OR] = 0.680; 95% confidence interval [CI], 0.507-0.912; p = 0.010; secondary analysis: OR = 0.578; 95% CI, 0.439-0.759; p = 0.00008). The robustness of the findings was supported by heterogeneity and horizontal pleiotropy analysis. Two colocalization analyses showed that alanine did not share a region of genetic variation with chalazion (primary analysis: PPH4 = 1.95%; secondary analysis: PPH4 = 25.3%). Moreover, previous studies have suggested that an increase in the degree of unsaturation is associated with an elevated risk of chalazion (OR = 1.216; 95% CI, 1.055-1.401; p = 0.007), with omega-3 fatty acids (OR = 1.204; 95% CI, 1.054-1.377; p = 0.006) appearing to be the major contributing factor, as opposed to omega-6 fatty acids (OR = 0.850; 95% CI, 0.735-0.982; p = 0.027). Conclusion: This study suggests that alanine and several unsaturated fatty acids are candidate molecules for mechanistic exploration and drug target selection in chalazion.

Two-photon fluorescence-guided precise photothermal therapy located in a single cancer cell utilizing bifunctional N-doped carbon quantum dots.

The utilization of carbon quantum dots (CQDs) for photothermal therapy has emerged as a hot research topic. However, there has been limited research on killing one single cancer cell which is critical in reducing unnecessary damage to the surrounding healthy tissues. In this work, we developed a two-photon fluorescence-guided precise photothermal therapy in a single human malignant melanoma (A375) cancer cell utilizing bifunctional N-doped CQDs. Resulting from the two-photon fluorescence of the CQDs, one single cancer cell can be located and simultaneously destroyed by the photothermal effect of the same CQDs. Specifically, the balanced two-photon absorption cross-section (7000 GM) and photoluminescence quantum yield (8.4%) of the CQDs enable the fluorescence-guided photothermal treatment to be achieved in only 5 s under the irradiation of 800 nm laser of 27.5 mW, much faster than the control experiment without the guidance of fluorescence. The heat generated by the aggregated CQDs is in sufficient amounts while being confined in a small area, as evidenced by the numerical simulations and photothermal experiments, to limit the range of thermal treatment in the cells. This work provides a new approach for realizing photothermal therapy with minimal damage and establishes a new application scenario of CQDs for precise tumor ablation.

Epigenetics research in eye diseases: a bibliometric analysis from 2000 to 2023.

CLINICAL RELEVANCE: A bibliometric analysis is a quantitative study that utilises methods such as citation analysis to evaluate research performance. A bibliometric analysis could provide a valuable reference for ophthalmic researchers to understand the trends in epigenetics research. BACKGROUND: The number of studies on epigenetics in eye diseases has exceeded 5,000, but the progress and scope of epigenetic research on eye diseases remain unclear. The study aimed to bibliometrically analyse epigenetic research conducted in eye diseases. METHODS: Studies concerning epigenetic research on eye diseases from 2000-2023 were searched using the Web of Science Core Collection. Following this, the included studies were analysed for citations, journals, keywords, authors, and countries, using the Bibliometrix package in R Studio. RESULTS: In total, 3758 studies were included in the analysis, including 3099 original articles, 599 reviews, 11 editorials, and 49 early access articles. Investigative Ophthalmology & Visual Science was the most published journal with 185 articles, and Proceedings of the National Academy of Sciences of the United States of America was the most cited journal, with 8727 citations. The journal with the highest h-index was Oncogene (h-index = 38).Renu A Kowluru from the Kresge Eye Institute, Wayne State University, Detroit, USA, had the most citations with 1,690 and the highest h-index (h-index = 23). China and the USA were the countries with the highest number of publications (1739) and total citations (40533), respectively. Furthermore, from 2000-2023, the top five frequent research topics were diabetic retinopathy, 522; microribonucleic acid, 469; retinoblastoma, 370; apoptosis, 268; and epigenetics, 206. CONCLUSIONS: The results of this bibliometric study provide the current status and trends of epigenetic research in eye diseases and will help researchers identify areas of current interest in the field, which should help highlight new research directions.

Pipecolic acid mitigates ferroptosis in diabetic retinopathy by regulating GPX4-YAP signaling.

Diabetic retinopathy (DR) is currently recognized as the leading cause of end-stage eye disease. Pipecolic acid, a metabolite, has a significant regulatory effect on several pathological processes. However, the exact mechanism by which it causes damage in diabetic retinopathy is unknown. Between September 2021 and December 2022, 40 patients were retrospectively examined and divided into two groups: the healthy group (n = 20) and the DR group (n = 20). Metabolomic analysis found that pipecolic acid plays an important role in this process. Streptozotocin-induced diabetic mice and high-glucose cultured human retinal capillary endothelial cells (HRCECs) were then treated with pipecolic acid. Several oxidative stress measurements and RNA sequencing of retinal cells were tested. A gene interaction study was conducted using bioinformatics. Comparison of serological metabolites between healthy volunteers and DR patients showed that pipecolic acid was significantly lower in DR patients, and there was a negative correlation between the level of pipecolic acid with blood glucose and glycated hemoglobin. Yes-associated protein (YAP) mRNA, Malondialdehyde (MDA), and reactive oxygen species (ROS) levels were significantly higher in diabetic mice, but glutathione peroxidase (GSH-Px) levels were significantly lower. Pipecolic acid significantly alleviated oxidative stress and YAP expression. The number of vascular tubes was significantly higher in the DR group, and pipecolic acid treatment significantly reduced tube formation. RNA-Sequencing analysis revealed that YAP and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) expression was reduced, and functional enrichment analysis revealed that ferroptosis and Hippo signaling pathways play an important role in this process. Additionally, pipecolic acid's ability to improve DR is diminished after YAP and GPX4 ablation. This study found that pipecolic acid, as a metabolite, may impede the progression of DR by inhibiting the YAP-GPX4 signaling pathway.

Effects of Special Therapeutic Footwear on the Prevention of Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: To reduce diabetic foot ulcer (DFU) occurrence or recurrence, diabetic therapeutic footwear is widely recommended in clinical practice for at-risk patients. However, the effectiveness of therapeutic footwear is controversial. Thus, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine whether special therapeutic footwear could reduce the incidence of DFU. Method: We systematically searched multiple electronic databases (Medline, EMBASE, and EMB databases) to identify eligible studies published from inception to June 11, 2021. The database search, quality assessment, and data extraction were independently performed by two reviewers. Efficacy (i.e., incidence of DFU) was explored using the R'meta' package (version 4.15-1). To obtain more robust results, the random-effects model and the Hartung-Knapp-Sidik-Jonkman method were selected to assess pooled data. Metaregression analysis and sensitivity analysis were performed to explore heterogeneity, and publication bias was assessed by a visual inspection of funnel plots and the AS-Thompson test. Results: Eight RCTs with a total of 1,587 participants were identified from the search strategy. Compared with conventional footwear, special therapeutic footwear significantly reduced the incidence of DFU (RR 0.49; 95% CI, 0.28-0.84), with no evidence of publication bias (P = 0.69). Unexpectedly, the effectiveness of special therapeutic footwear had a reverse correlation with the intervention time (coefficient = 0.085, P < 0.05) in the metaregression analysis. Conclusion: Special therapeutic footwear with offloading properties is effective in reducing the incidence of DFU. However, the effect may decrease gradually over time. Despite undefined reasons, the optimal utility time and renewal frequency of special therapeutic footwear should be considered.

Amniotic fluid mesenchymal stem cells repair mouse corneal cold injury by promoting mRNA N4-acetylcytidine modification and ETV4/JUN/CCND2 signal axis activation.

Severe corneal injury is one of the main causes of loss of visual function. Mesenchymal stem cells (MSCs) have the ability to repair damaged cells in vivo. The present study aimed to explore whether MSCs could function as a cell therapy tool to replace traditional methods to treat corneal injury. CD44 + /CD105 + mesenchymal stem cells isolated from mouse amniotic fluid (mAF-MSCs) were injected into mice after cryoinjury to induce corneal endothelial cell injury. Histopathological assays indicated that mAF-MSCs could promote the growth of corneal epithelial cells, reduce keratitis, and repair the corneal damage caused by low temperature. cDNA microarray analysis revealed that the mAF-MSCs affected the expression patterns of mRNAs related to cell proliferation and differentiation pathways in the mice after transplantation. The results of quantitative real-time PCR and western blotting revealed that NAT12, NAT10, and the ETV4/JUN/CCND2 signaling axis were elevated significantly in the mAF-MSC-transplantation group, compared with those in the phosphate-buffered saline-treated groups. High performance liquid chromatography-mass spectroscopy results revealed that mAF-MSCs could promote mRNA N4-acetylcytidine (ac4C) modification and high expression of N-acetyltransferase in the eyeballs. RNA immunoprecipitation-PCR results showed that a specific product comprising Vegfa, Klf4, Ccnd2, Jun, and Etv4 mRNA specific coding region sites could be amplified using PCR from complexes formed in mAF-MSC-transplanted samples cross-linked with anti-ac4C antibodies. Thus, mouse amniotic fluid MSCs could repair the mouse corneal cold injury by promoting the ETV4/JUN/CCND2 signal axis activation and improving its stability by stimulating N4-acetylcytidine modification of their mRNAs.

[A preliminary study on the early diagnosis of sinus dysfunction in patients with obstructive sleep apnea syndrome].

OBJECTIVES: To observe the characteristics of sinus dysfunction (SD) in patients with obstructive sleep apnea syndrome (OSAHS) and to explore the method for early detection of SD in these patients. METHODS: From January 2007 to June 2008, 119 snorers were recruited. All of them underwent polysomnography (PSG) examination and received atropine test under ultramicroelectrocardiogram (UMECG). Based on the results of atropine test, they were divided into 2 groups: the UMECG group (n = 78) including subjects diagnosed as having SD by a positive result of atropine test with UMECG, and the non-UMECG group (n = 41) including subjects with a negative result of atropine test. Comparison was made for the incidence of OSAHS between the 2 groups and the diagnostic sensitivities for SD between UMECG and PSG electrocardiogram (SD(PSG)). The association was also observed between PSG parameters and SD(PSG). RESULTS: The incidence of OSAHS in the non-UMECG group was significantly higher than that in the UMECG group (31% vs 55%, P < 0.05). SD(PSG) was not detected in the non-UMECG group. In the UMECG group, SD(PSG)/UMECG was 26/43 (60%) in the OSAHS subjects and 29/35 (83%) in the non-OSAHS subjects (P < 0.05). Of the OSAHS subjects in the UMECG group, SD(PSG)/UMECG was 10/20 (50%) in the mild to moderate OSAHS subjects and 16/23 (70%) in the severe OSAHS subjects (P < 0.05). Compared with the OSAHS subjects with UMECG but without SD(PSG), the average duration of apnea events as well as the longest apnea event were prolonged while the minimal SaO2 was lower in those OSAHS patients with SD(PSG). Among all of the 17 OSAHS subjects with SD(UMECG) but with out SD(PSG), there were 13 subjects (76%) with a fastest sinus heart rate slower than 90 beats/min even though they also had hypoxemia during sleep. CONCLUSIONS: SD was associated with OSAHS. The actual incidence of SD may be underestimated by PSG only, especially in those with mild to moderate OSAHS. SD should be suspected in OSAHS patients whose fastest sinus rate is lower than 90 beats/min in spite of hypoxemia. UMECG was more sensitive for early detection of SD.

Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence-Accelerated Mouse Prone 8 Mice.

OBJECTIVE: To investigate the preventive treatment effects of electroacupuncture (EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: The 5-month-old male SAMP8 and age-matched homologous normal aging mice (SAMR1) were adopted in this study. EA stimulation at Baihui (GV 20) and Yintang (EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-ß (A ß) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. RESULTS: After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, A ß expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. CONCLUSION: EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting A ß-containing aggregates.

[Association between severe obstructive sleep apnea syndrome and sinus dysfunction].

OBJECTIVE: To preliminarily investigate the association between severe obstructive sleep apnea syndrome (OSAS) and sinus dysfunction (SD). METHODS: From March of 2005 to June of 2006, 70 patients with severe OSAS and 36 simple snorers underwent electrocardiography by polysomnography. In order to compare their sinus function and analyse the risk factors of SD, atropine test with simultaneous monitoring of ultramicroelectrocardiogram (UMECG) was performed in those with the lowest heart rate < 40 pbm, or the highest sinus heart rate < 90 bpm, or the longest R-R interval > 2.0 seconds. All data were statistically analyzed with SPSS 13.0 software. RESULTS: Sixteen of the 70 severe OSAS patients were diagnosed as with SD with an incidence of 22.9%, significantly higher than that in the patients with simple snore (2/36, 5.6%, P = 0.025). In 70 patients with severe OSAS (16 patients with SD), single factor analysis indicated that there was a significant difference between those with SD and those without SD in Nadir pulse oxygen saturation, longest apnea duration and incidence of coronary artery disease (T test, P = 0.002; T test, P = 0.029; Fisher's Exact test, P = 0.043), and Logistic regressive analysis showed that the risk factors of SD were the decrease of Nadir pulse oxygen saturation (P = 0.003, OR < 0.001, 95% CI 0.000 - 0.016) and age (P = 0.055, OR = 1.053, 95% CI 1.007 - 1.125). CONCLUSIONS: The incidence of SD in patients with severe OSAS is higher than that in simple snore. Lower Nadir pulse oxygen saturation during sleep was the major risk factor for occurrence of SD in patients with severe OSAS.