Moderating effects of preoperative knee pain and pain catastrophizing on the relation between COMT rs4680 genotypes and chronic postsurgical pain in total knee arthroplasty patients.

BACKGROUND: The Catechol-O-methyltransferase (COMT) gene, responsible for encoding an enzyme crucial in the metabolism of catecholamines, is known to play a significant role in pain perception. Polymorphisms within this gene, particularly the COMT rs4680 genotypes, have been linked to various acute pain phenotypes. This prospective cohort study examines interactions among the genetic polymorphism COMT rs4680 genotypes, preoperative knee pain, and pain catastrophizing in chronic postsurgical pain (CPSP) at 3, 6, and 12 months post-total knee arthroplasty (TKA). STUDY DESIGN: A total of 280 patients undergoing primary unilateral TKA participated, sharing demographic details, preoperative knee pain levels, psychological variables (pain catastrophizing), and COMT rs4680 genotyping via venous blood samples. Telephone interviews at specified intervals enabled the application of binary logistic regressions and interaction models. RESULTS: Significant influences of preoperative knee pain and pain catastrophizing on postsurgical outcomes were observed. Specifically, at the first time point (T1, 3 months post-TKA), a notable moderation effect was identified in preoperative knee pain (R2 change = 0.026, p = 0.026). The Johnson-Neyman regions of significance (RoS) indicated these moderation effects were significant above a threshold of 17.18 (p = 0.05), accounting for 26.4%. At the third time point (T3, 12 months post-TKA), a complex three-way interaction among genotypes (GG, GA, and AA carriers) was evident, resulting in an R2 change of 0.051 (p = 0.009). Here, the RoS for pain catastrophizing was above 32.74 for 30.5% of GG genotype carriers, above 22.38 for 50.8% of GA carriers, and below 11.94 for 63.2% of AA carriers. CONCLUSION: This study illuminates the significant role of the COMT Val158Met rs4680 polymorphism in susceptibility to prolonged pain following TKA. It also elucidates how these genetic genotypes interplay with preoperative knee pain and pain catastrophizing. Such intricate genetic-psychological-pain relationships necessitate additional investigation to confirm these findings and potentially guide post-TKA pain management strategies.

Association of plasma galectin-3 and fetuin-A levels with diabetic retinopathy in type 2 diabetes mellitus patients.

INTRODUCTION: Galectin-3 (Gal-3) and fetuin-A (Fet-A) are cytokines that participate in inflammation and insulin resistance. Previous studies have found that altered Gal-3 and Fet-A levels in circulation correlate with diabetic complications. However, whether they are all associated with diabetic retinopathy (DR) has been little investigated. The aim of this study was to assess plasma Gal-3 and Fet-A concentrations, and to investigate their associations with the presence of DR in type 2 diabetes mellitus (T2DM) patients. MATERIAL AND METHODS: A total of 100 T2DM patients were enrolled, among which there were 50 patients without DR (non diabetic retinopathy, NDR group) and 50 patients with DR (DR group). Clinical parameters were collected, and plasma Gal-3 and Fet-A levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Both Gal-3 and Fet-A were found to be increased in DR patients with respect to NDR controls, and Gal-3 correlated positively with Fet-A. Bivariate correlation analysis revealed that Gal-3 levels were positively correlated with haemoglobin A1c (HbA1c), while Fet-A correlated negatively with fasting C peptide (FC-P) and positively with homocysteine (Hcy). Binary logistic regression suggested that elevated Gal-3 and Fet-A levels were related to increased risk of DR. ROC curve displayed that the combination of Fet-A and Gal-3 exhibited better diagnostic value for DR. CONCLUSIONS: Both Gal-3 and Fet-A were elevated in the circulation of DR patients, and they were positively associated with the occurrence of DR. The combination of 2 indicators showed better diagnostic value for DR.

Updates on RPE cell damage in diabetic retinopathy (Review).

Diabetic retinopathy (DR) is a microvascular complication of diabetes. The retinal pigment epithelium (RPE) forms the outer layer of the blood­retinal barrier and serves a role in maintaining retinal function. RPE cell injury has been revealed in diabetic animal models, and high glucose (HG) levels may cause damage to RPE cells by increasing the levels of oxidative stress, promoting pro­inflammatory gene expression, disrupting cell proliferation, inducing the endothelial­mesenchymal transition, weakening tight conjunctions and elevating cell death mechanisms, such as apoptosis, ferroptosis and pyroptosis. Non­coding RNAs including microRNAs, long non­coding RNAs and circular RNAs participate in RPE cell damage caused by HG levels, which may provide targeted therapeutic strategies for the treatment of DR. Plant extracts such as citrusin and hesperidin, and a number of hypoglycemic drugs, such as sodium­glucose co­transporter 2 inhibitors, metformin and glucagon­like peptide­1 receptor agonists, exhibit potential RPE protective effects; however, the detailed mechanisms behind these effects remain to be fully elucidated. An in­depth understanding of the contribution of the RPE to DR may provide novel perspectives and therapeutic targets for DR.

Omentin-1 and diabetes: more evidence but far from enough.

AIMS AND BACKGROUND: Omentin-1 (oment-1) is a type of adipokines that is mainly expressed in visceral fat tissue. Based on accumulating evidence, oment-1 is closely related to diabetes and its complications. However, so far data about oment-1 and diabetes is fragmented. In this review, we focus on the role of oment-1 on diabetes, including its possible signalling pathways, the correlation of circulating omens-1 levels with diabetes and its complications. METHODS: The web of PubMed was searched for articles of relevant studies published until February, 2023. RESULTS AND CONCLUSIONS: Oment-1 might exert its effects by inhibiting the NF-κB pathway and activating the Akt and AMPK-dependent pathways. The level of circulating oment-1 is negatively correlated with the occurrence of type 2 diabetes and some complications, including diabetic vascular disease, cardiomyopathy, and retinopathy, which can be affected by anti-diabetic therapies. Oment-1 could be a promising marker for screening and targeted therapy for diabetes and its complications; however, more studies are still needed.

Dynamic Changes of ORF1ab and N Gene Ct Values in COVID-19 Omicron Inpatients of Different Age Groups - Beijing Municipality, China, November-December 2022.

Introduction: In November 2021, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was identified as the variant of concern and has since spread globally, replacing other cocirculating variants. To better understand the dynamic changes in viral load over time and the natural history of the virus infection, we analyzed the expression of the open reading frames 1ab (ORF1ab) and nucleocapsid (N) genes in patients infected with Omicron. Methods: We included patients initially admitted to the hospital for SARS-CoV-2 infection between November 5 and December 25, 2022. We collected daily oropharyngeal swabs for quantitative reverse transcriptase-polymerase chain reaction tests using commercial kits. We depicted the cycle threshold (Ct) values for amplification of ORF1ab and N genes from individual patients in age-specific groups in a time series. Results: A total of 480 inpatients were included in the study, with a median age of 59 years (interquartile range, 42 to 78; range, 16 to 106). In the <45-year-old age group, the Ct values for ORF1ab and N gene amplification remained below 35 for 9.0 and 11.5 days, respectively. In the ≥80-year-old age group, the Ct values for ORF1ab and N genes stayed below 35 for 11.5 and 15.0 days, respectively, which was the longest among all age groups. The Ct values for N gene amplification took longer to rise above 35 than those for ORF1ab gene amplification. Conclusion: The time to test negative varied among different age groups, with viral nucleic acid shedding taking longer in older age groups compared to younger age groups. As a result, the time to resolution of Omicron infection increased with increasing age.

The duration of postoperative analgesic use after total knee arthroplasty and nomogram for predicting prolonged analgesic use.

Background: Total knee arthroplasty is currently a reliable treatment for end-stage knee osteoarthritis. However, chronic postsurgical pain (CPSP) is substantially thought to reduce patient satisfaction. NSAID-based oral analgesics were used to manage CPSP, but research on the duration of postoperative analgesic use (DAU) and prolonged analgesic use (PAU) are presently scarce. Methods: Preoperative, perioperative, and one-year or above postoperative follow-up data were collected from 162 patients who underwent total knee arthroplasty between 1 June 2018 and 1 March 2019, and the DAU and the discontinuation time of each patient after discharge were recorded. Observational statistical analysis, diagnostic test, and predictive nomogram construction were performed on the collected data. Results: The 3-month DAU has good diagnostic utility for poor outcome of postoperative months twelve (POM12). The constructed nomogram shows that gender, preoperative Numeric Rating Scale (NRS) movement pain scores, duration of surgery, postoperative days three (POD3) moderate to severe movement pain, and POD3 pain rescue medication were significant prognostic predictors of PAU after discharge. The area under the curve (AUC) of the 3-month, 6-month, and 12-month nomogram receiver operating characteristic (ROC) curves were calculated to be 0.741, 0.736, and 0.781. Conclusion: PAU was defined as more than three months of NSAID-based oral analgesic use after TKA. Prognostic predictors of PAU after TKA were identified, and visualized nomogram was plotted and evaluated. The evaluation indicated that the prediction model had the good predictive ability and was a valuable tool for predicting PAU after discharge.

Inhibition of galectin-3 ameliorates high-glucose-induced oxidative stress and inflammation in ARPE-19 cells.

PURPOSE: Retinal pigment epithelium (RPE) has been found to be participated in the pathogenesis of DR in recent years. Galectin-3 (Gal-3) is involved in many diabetic complications and ophthalmological diseases. However, the role of Gal-3 in RPE cells in DR remains unknown. This study aims to investigate the role of Gal-3 in ARPE-19 cells under high glucose treatment. MATERIALS AND METHODS: ARPE-19 cells were cultured under normal or high glucose (HG) for 48 h. Expression of Gal-3 was inhibited by Si-Gal-3 transfection. Apoptosis was checked by flow cytometry. Oxidative stress was checked by measuring ROS, MDA levels, and SOD activities. Occludin and ZO-1 expression were checked by immunofluorescence staining. Genes involved in inflammatory response were measured by real-time PCR and Western blot. RESULTS: Gal-3 expression could be increased by HG treatment in ARPE-19 cells. Gal-3 knockdown might reduce oxidative stress, apoptosis, and gene expression of VCAM-1, ICAM-1, and integrin-ß1 induced by HG treatment. The gene expression of IL-1ß could be markedly promoted by HG treatment and this increasement was partly alleviated by Gal-3 knockdown only at the mRNA level. The reduced expression of ZO-1 and occludin caused by HG could also be improved by Gal-3 knockdown. CONCLUSION: Gal-3 participated in increased oxidative stress and inflammatory response caused by HG in ARPE-19 cells.

Prevalence and Predictors of Chronic Pain with Two-Year Follow-Up After Knee Arthroplasty.

Background: Pain relief is the most important issue in the long-term outcome of arthroplasty surgery, with nearly one-third of patients still suffered persistent pain and caused dissatisfaction after the surgery. Methods: A total of 713 patients underwent primary elective primary TKA and UKA were included consecutively between July 2018 and December 2019, using binary logistic method to analyze the data. Results: The prevalence of CPSP at rest and on movement at 2-year was 12.1% and 37.7% respectively after primary knee arthroplasty and CPSP at rest factors included: age above 80 (odds ratio [OR]= 6.72, 95% confidence interval [CI] 1.58 to 28.56), BMI above 30 (2.339, 1.02 to 5.383), and moderate to severe pain variables: preoperative pain, (1.95, 1.11 to 3.41); APSP on movement, 4.9 (2.31-10.6); and follow-up contralateral knee pain-at-rest scores (12.6, 5.5 to 28.5). Factors associated with presence of CPSP on movement included: no smoking (2.59, 1.07 to 6.26); and moderate to severe pain variables: preoperative pain, (1.57, 1.073 to 2.30); APSP at rest, (1.85, 1.13 to 3.02); APSP on movement, 6.11 (3.82 to 9.78); and follow-up contralateral knee pain-on-movement scores, 3.22 (2.08 to 5.00). Factors to occurrence of moderate to severe CPSP on movement include: presence of COPD (12.20, 2.19 to 67.98); and moderate to severe pain variables: preoperative pain (2.36, 1.32 to 4.23); APSP on movement (4.68, 1.95 to 11.25); and follow-up contralateral knee pain-on-movement scores (2.71, 1.66 to 4.42). Conclusion: Prevention strategies should be targeted to different types of pain, and the comorbidity of COPD undergoing knee arthroplasty should receive early identification and attention.

Prognosis of Neurological Improvement in Inpatient Acute Ischemic Stroke Survivors: A Propensity Score Matching Analysis.

OBJECTIVES: Stroke has become a national concern in China. Early prediction of stroke benefits patients and aids medical professionals in clinical decision making and rehabilitation plans to improve successful outcomes. To identify prediction factors influencing short-term outcomes in patients with acute ischemic stroke (AIS). MATERIALS AND METHODS: This was a hospital-based prospective observational study. Recovery of neurological improvement was represented by a percent reduction in the National Institutes of Health Stroke Scale (NIHSS) at discharge. We performed propensity score matching (PSM) to balance the NIHSS at admission and compared NIHSS scores before and after matching with PSM criteria. Finally, we assessed the prognosis of neurological improvement and patient-related variables. RESULTS: In the matched cohort, 92 pairs were matched by NIHSS admission after PSM. Modified Barthel Index, modified Rankin scale, NIHSS on admission, hypertension, sleep time, and Montreal Cognitive Assessment (MoCA) were statistically different between the two groups (P<0.05) before matching. Multivariable analysis identified two factors independently associated with neurological improvement: diabetes (P=0.030; adjusted odds ratio, 2.129; 95% confidence interval [CI] 1.078-4.026) and MoCA (P<0.001; adjusted odds ratio, 5.385; 95% CI 2.278-12.730). CONCLUSION: Consistent with previous studies, diabetes affected the short-term outcomes of AIS, while cognitive impairment had a negative effect on long-term AIS prognosis.Diabetes and early cognitive impairment have adverse effects on short-term prognosis after AIS.

A peptide derived from melanotransferrin delivers a protein-based interleukin 1 receptor antagonist across the BBB and ameliorates neuropathic pain in a preclinical model.

Delivery of biologic drugs across the blood-brain barrier is becoming a reality. However, the solutions often involve the assembly of complex multi-specific antibody molecules. Here we utilize a simple 12 amino-acid peptide originating from the melanotransferrin (MTf) protein that has shown improved brain delivery properties. 3D confocal fluorescence microscopic analysis demonstrated brain parenchymal localisation of a fluorescently labelled antibody (NIP228) when chemically conjugated to either the MTf peptide or full-length MTf protein. Measurement of plasma kinetics demonstrated the MTf peptide fusions had very similar kinetics to an unmodified NIP228 control antibody, whereas the fusion to MTf protein had significantly reduced plasma exposure most likely due to a higher tissue distribution in the periphery. Brain exposure for the MTf peptide fusions was significantly increased for the duration of the study, exceeding that of the fusions to full length MTf protein. Using a neuropathic pain model, we have demonstrated that fusions to interleukin-1 receptor antagonist (IL-1RA) are able to induce significant and durable analgesia following peripheral administration. These data demonstrate that recombinant and chemically conjugated MTf-based brain delivery vectors can deliver therapeutic levels of drug to the central nervous system.

Multiple symmetric lipomatosis and gynecomastia: A case report and relative literature review.

Multiple symmetric lipomatosis is a rare disease characterized by a symmetrical accumulation of massive adipose tissue on the neck, the superior part of the trunk, and limbs. Here, we reported an extremely rare case of multiple symmetric lipomatosis in a 46-year-old Chinese man, who has a history of heavy drinking and smoking and presented with diffuse lipomatosis and bilateral breast enlargement. Hyperuricemia and impaired glucose tolerance test were all found in this patient. A brief review of the literature was also made in this article.

Long-Term Effectiveness and Cost-Effectiveness of Metformin Combined with Liraglutide or Exenatide for Type 2 Diabetes Mellitus Based on the CORE Diabetes Model Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with ß cell impairment. Agonists of the glucagon-like peptide 1 (GLP-1) receptor (such as liraglutide and exenatide) can increase the number of pancreatic ß cells and improve cell function. These drugs contribute to the long-term control of T2DM. OBJECTIVE: To evaluate the cost-effectiveness of metformin combined with liraglutide or exenatide in Chinese patient with T2DM. METHODS: Patients with T2DM from the Third Hospital of Hebei Medical University were treated with oral metformin combined with liraglutide (0.6 mg/day, could be increased by 0.6 mg weekly until 1.2 or 1.8 mg) or exenatide (5 µg bid for four weeks, increased to 10 µg bid). The computer simulation model CORE was used to calculate the 30-year expected life expectancy, quality-adjusted life years (QALY), direct costs, HbA1c levels, body mass index (BMI), and the incidence of cardiovascular, renal, and ocular complications of T2DM. Patients were followed up for 52 weeks. Medication costs were calculated according to retail prices in China. A 3% annual discount was adopted in this study. RESULTS: The 30-year simulation showed that the total direct medical costs were lower using liraglutide compared to exenatide by 2130 RMB/QALY yearly, while the expected life expectancy and QALY were increased by 0.471 years and 0.388, respectively, using liraglutide with an incremental cost-effectiveness of -11,550 RMB/QALYs. CONCLUSION: Liraglutide 1.2 mg/day was superior to exenatide 10 µg bid with respect to cost-effectiveness in Chinese patients with T2DM.

Reliability and validity of the Chinese version of reporting of clinical adverse events scale (C-RoCAES).

BACKGROUND: Adverse event is a crucial issue affecting patient's safety of healthcare services. To assess nurses' attitude of reporting adverse events is important to establish a safe environment for patients. However, no relevant instrument has been validated and used in China. This study was to examine validity and reliability of Chinese version of Reporting of Clinical adverse Event Scale (C-RoCAES). MATERIAL AND METHODS: Chinese version of 25-item RoCAES was used in a sample of 1557 nurses. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were selected for construct validity test. Internal consistency was also examined. RESULTS: After CFA and EFA, two items were removed and two items loaded on different factors in our sample. Five factors were generated, including perceived blame, perceived criteria for identifying events that should be reported, perceptions of colleagues' expectations, perceived benefits of reporting and perceived clarity of reporting procedures. Cronbach's alpha for the total scale and subscales ranged from 0.70 to 0.85. CONCLUSION: C-RoCAES is applicable to healthcare services of China. The instrument provide information for the providers of healthcare services to develop staff education regarding patient safety, and also help them to evaluate strategies of preventing adverse events in clinical practice in China.

Adiponectin and its receptors in chronic hepatitis B patients with metabolic syndrome in China.

BACKGROUND/AIMS: Adiponectin can initiate a broad range of metabolic and immunological effects. Little is known about the role of adiponectin in hepatitis B related liver disease and metabolic syndrome (MS). METHODOLOGY: We studied 138 patients with untreated chronic hepatitis B (CHB), who were from Beijing Ditan hospital in 2005 to 2009. According to MS, two groups (65 with MS vs. 73 without MS) were established. They were compared with characteristics and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2). RESULTS: In the group of CHB patients with MS, the levels of LDH, γ-GT, FPG, FINS, HOMA-IR, HOMA-ß, TG and HBeAg positive were significantly higher than those in the group without MS (p<0.05). Liver steatosis in the group with MS is significantly more severe than that in the group without MS (p<0.001). With binary logistic regression analyses, BMI and HOMA-IR showed independent predictors to MS in patients with CHB. In patients with chronic HBV, the insulin sensitizing adipokine adiponectin and its receptor AdipoR2 was associated with diabetes in patients with CHB and MS. CONCLUSIONS: Our findings showed the CHB patients with MS may be presence of more severe steatosis. MS in CHB patients may be closely correlated with insulin resistance and less effect of viruses. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with MS.

[Cleavage of HCV by HCV specific deoxyribozyme in vitro].

OBJECTIVE: To study the cleavage activity of specific deoxyribozyme to hepatitis C virus in vitro. METHODS: Three deoxyribozymes were designed to cleave at sites 157, 168, 173 in HCV 5'-noncoding region with the active region of 5'-GGCTAGCTACAACGA-3' respectively. Plasmid pCMV/T7-NCRC -Delta Luc was completely linearized with restriction endonuclease Xba I. HCV RNA5'-NCRC was transcribed in vitro from the linearized products and radiolabelled with [alpha-32P] UTP. Under the conditions of 37 degrees C, pH7.5, Mg2+ 10 mmol/L, the three deoxyribozymes were mixed with substrate RNA individually for 120 minutes and then the reactions were terminated. The cleavaged products were separated with 8% denaturated polyacrylamide gel electrophoresis and displayed by autoradiography. DRz3 was mixed with the substrate RNA at different Mg2+ concentrations. The cleavage efficiency was analyzed with a gel document action analyzing systems. RESULTS: Under the adopted conditions the three deoxyribozymes efficiently cleaved to the target RNA in vitro and the cleavage activity of DRz3 was increased with the increase of Mg2+ concentration. CONCLUSION: The designed deoxyribozymes can cleave 5'-NCR mRNA of HCV efficiently in vitro and it is dose-respondent to Mg2+ concentration.

[Study on the cleavage activity of U1 small nuclear RNA chimeric ribozyme against HCV RNA in vitro].

OBJECTIVE: To study the cleavage activity on the HCV RNA of a chimeric recombinant of HCV specific ribozyme and U1 small nuclear RNA, which compartmentalizes within the nucleolus. METHODS: The third stem-loop sequence of human U1 snRNA (position 95-116) within pBSIISK+ U1 was substituted by hammerhead ribozyme against HCV RNA by PCR and cloning methods, and the constructed plasmid was named pBSIISK+ (U1-Rz). Then the whole gene fragment of the chimeric ribozyme was cloned into a pGEM-T vector under the control of T7 promoter, and the constructed plasmid was named pGEM- (U1-Rz). The pGEM- (U1-Rz) and pGEM-Rz (containing the same ribozyme sequence as that in U1-Rz) transcripts as enzyme were transcribed in vitro. Also the (32)P-labeled pCMV/T7-NCRC luc (containing the gene sequence of the whole 5'-NCR and part core of HCV RNA) transcripts as target-RNAs were transcribed in vitro. The enzymes were incubated with the target RNAs under different conditions and autoradiographed after denaturing gel-electrophoresis. RESULTS: The sequencing result showed that the construction of U1 snRNA chimeric ribozyme was correct. Compared with the ribozyme alone, both of them were active at 37 degree C and with Mg2+ (10 mmol/L) and TrisCl (10 mmol/L, pH7.9), and there was no remarkable difference between them. The cleavage activity of the chimeric ribozyme increased with the prolongation of reaction time and increment of enzyme concentration. CONCLUSION: Both ribozyme and U1 snRNA chimeric ribozyme exhibited specifically catalytic activity against HCV RNA in vitro. There was no remarkable difference between their cleavage efficiencies.

Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain.

Dendritic cells (DCs) can present extracellularly derived antigens in the context of major histocompatibility complex (MHC) class I molecules, a process called cross-presentation. Although recognized to be important for priming of T cell responses to many viral, bacterial and tumor antigens, the mechanistic details of this alternative antigen-presentation pathway are poorly understood. We demonstrate here the existence of an endolysosomal compartment in DCs where exogenously derived peptides can be acquired for presentation to T cells, and show that the MHC class I cytoplasmic domain contains a tyrosine-based targeting signal required for routing MHC class I molecules through these compartments. We also report that transgenic mice expressing H-2K(b) with a tyrosine mutation mount inferior H-2K(b)-restricted cytotoxic T lymphocyte responses against two immunodominant viral epitopes, providing evidence of a crucial function for cross-priming in antiviral immunity.