Home-based vs center-based exercise on patient-reported and performance-based outcomes for knee osteoarthritis: a systematic review with meta-analysis.

Background: Home-based exercise (HBE) represents an alternative to increase the accessibility of rehabilitation programs and relieve the burden on the health care system for people with knee osteoarthritis. Objectives: To summarize for the first time the effectiveness of HBE as compared to center-based exercise (CBE), both with and without HBE, on patient-reported and performance-based outcomes in people with KOA. Methods: Searches were conducted on PubMed, Cochrane, Embase, Web of Science, and Scopus until March 10, 2023, without date or language restrictions. Randomized controlled trials investigating HBE versus CBE or HBE combined with CBE for people with KOA were eligible. The primary outcomes were patient-reported: pain, physical disability, and quality of life. The secondary outcomes were performance-based: walking ability, lower limb muscle strength, and balance function. Risk of bias was assessed with the Cochrane Risk of Bias tool and quality of evidence according to the GRADE. Results: Eleven trials involving 956 participants were included. There was no difference in short-term pain (SMD, 0.22 [95% CI, -0.04 to 0.47], p = 0.09; I2 = 0%), physical disability (SMD, 0.17 [95% CI, -0.19 to 0.54], p = 0.35; I2 = 0%), walking ability (SMD, -0.21 [95% CI, -0.64 to 0.22], p = 0.33; I2 = 35%) and lower limb muscle strength (SMD, -0.24 [95% CI, -0.88 to 0.41], p = 0.47; I2 = 69%) between HBE and CBE. HBE combined with CBE has better benefits compared with HBE alone in short-term pain (SMD, 0.89 [95% CI, 0.60 to 1.17], p < 0.001; I2 = 11%) and physical disability (SMD, 0.25 [95% CI, 0.00 to 0.50], p = 0.05; I2 = 0%). Conclusion: Based on limited evidence, HBE is as effective as CBE on short-term pain, physical disability, walking ability, and lower limb muscle strength in people with knee osteoarthritis. Furthermore, combining HBE with CBE may enhance the overall efficacy of the intervention. Systematic review registration: PROSPERO, CRD42023416548.

NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis.

BACKGROUND: NUDT21 (Nudix Hydrolase 21) has been shown to play an essential role in multiple biological processes. Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world. However, the biological function of NUDT21 in PAAD remains rarely understood. The aim of this research was to identify the prediction value of NUDT21 in diagnosis, prognosis, immune infiltration, and signal pathway in PAAD. METHODS: Combined with the data in online databases, we analyzed the expression, immune infiltration, function enrichment, signal pathway, diagnosis, and prognosis of NUDT21 in PAAD. Then, the biological function of NUDT21 and its interacted protein in PAAD was identified through plasmid transduction system and protein mass spectrometry. Expression of NUDT21 was further verified in clinical specimens by immunofluorescence. RESULTS: We found that NUDT21 was upregulated in PAAD tissues and was significantly associated with the diagnosis and prognosis of pancreatic cancer through bioinformatic data analysis. We also found that overexpression of NUDT21 enhanced PAAD cells proliferation and migration, whereas knockdown NUDT21 restored the effects through in vitro experiment. Moreover, NDUFS2 was recognized as a potential target of NUDT21.We further verified that the expression of NDUFS2 was positively correlated with NUDT21 in PAAD clinical specimens. Mechanically, we found that NUDT21 stabilizes NDUFS2 and activates the PI3K-AKT signaling pathway. CONCLUSION: Our investigation reveals that NUDT21 is a previously unrecognized oncogenic factor in the diagnosis, prognosis, and treatment target of PAAD, and we suggest that NUDT21 might be a novel therapeutic target in PAAD.

Multidimensional Predictors of Cancer-Related Fatigue Based on the Predisposing, Precipitating, and Perpetuating (3P) Model: A Systematic Review.

Cancer-related fatigue (CRF) is a widespread symptom with high prevalence in cancer patients, seriously affecting their quality of life. In the context of precision care, constructing machine learning-based prediction models for early screening and assessment of CRF is beneficial to this situation. To further understand the predictors of CRF for model construction, we conducted a comprehensive search in PubMed, Web of Science, Embase, and Scopus databases, combining CRF with predictor-related terms. A total of 27 papers met the inclusion criteria. We evaluated the above studies into three subgroups following the predisposing, precipitating, and perpetuating (3P) factor model. (1) Predisposing factors-baseline fatigue, demographic characteristics, clinical characteristics, psychosocial traits and physical symptoms. (2) Precipitating factors-type and stage of chemotherapy, inflammatory factors, laboratory indicators and metabolic changes. (3) Perpetuating factors-a low level of physical activity and poorer nutritional status. Future research should prioritize large-scale prospective studies with emerging technologies to identify accurate predictors of CRF. The assessment and management of CRF should also focus on the above factors, especially the controllable precipitating factors, to improve the quality of life of cancer survivors.

CD72, a new immune checkpoint molecule, is a novel prognostic biomarker for kidney renal clear cell carcinoma.

BACKGROUND: The incidence and mortality of clear cell carcinoma of the kidney increases yearly. There are limited screening methods and advances in treating kidney renal clear cell carcinoma (KIRC). It is important to find new biomarkers to screen, diagnose and predict the prognosis of KIRC. Some studies have shown that CD72 influences the development and progression of colorectal cancer, nasopharyngeal cancer, and acute lymphoid leukemia. However, there is a lack of research on the role of CD72 in the pathogenesis of KIRC. This study aimed to determine whether CD72 is associated with the prognosis and immune infiltration of KIRC, providing an essential molecular basis for the early non-invasive diagnosis and immunotherapy of KIRC. METHODS: Using TCGA, GTE, GEO, and ImmPort databases, we obtained the differentially expressed mRNA (DEmRNA) associated with the prognosis and immunity of KIRC patients. We used the Kruskal-Wallis test to identify clinicopathological parameters associated with target gene expression. We performed univariate and multivariate COX regression analyses to determine the effect of target gene expression and clinicopathological parameters on survival. We analyzed the target genes' relevant functions and signaling pathways through enrichment analysis. Finally, the correlation of target genes with tumor immune infiltration was explored by ssGSEA and Spearman correlation analysis. RESULTS: The results revealed that patients with KIRC with higher expression of CD72 have a poorer prognosis. CD72 was associated with the Pathologic T stage, Pathologic stage, Pathologic M stage, Pathologic N stage, Histologic grade in KIRC patients, Laterality, and OS event. It was an independent predictor of the overall survival of KIRC patients. Functional enrichment analysis showed that CD72 was significantly enriched in oncogenic and immune-related pathways. According to ssGSEA and Spearman correlation analysis, CD72 expression was significantly associated with tumor immune cells and immune checkpoints. CONCLUSION: Our study suggests that CD72 is associated with tumor immunity and may be a biomarker relevant to the diagnosis and prognosis of KIRC patients.

Association between maternal rheumatoid arthritis and small for gestational age neonates: a systematic review and meta-analysis.

Background: According to reports, maternal rheumatoid arthritis (RA) has been suggested as a possible adverse factor for developing small for gestational age (SGA) in offspring. However, some studies have also indicated a need for a more statistically significant association between the two. Understanding the relationship between maternal RA and the risk of SGA is crucial for identifying potential adverse outcomes and implementing appropriate interventions. Therefore, this study aims to elucidate the association between maternal RA and the risk of offspring developing SGA. Methods: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42022357590). A systematic literature search was conducted to identify eligible studies up to August 2022. Quality assessment was performed according to the Newcastle-Ottawa scale. The Q test and I2 test tested and estimated heterogeneity among studies. Odds ratios (ORs) with 95% CI were calculated using random or fixed effects models depending on the heterogeneity. Subgroup analyses, sensitivity analyses, and publication bias assessments were also performed. Results: Seven studies, including 12,323,918 participants, were included in the analysis. The results showed a statistically significant association between maternal RA and SGA (OR = 1.70, 95% CI = 1.29-2.23, p < 0.001). Sensitivity analysis showed stable results. The funnel plot of the symmetric distribution and the results of Begg's and Egger's tests showed no publication bias. Conclusion: Maternal RA is associated with an increased risk of SGA in offspring. However, more studies are still needed to explore the potential mechanisms underlying maternal RA and SGA association. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022357590].

Association between pregnant women with rheumatoid arthritis and preeclampsia: A systematic review and meta-analysis.

BACKGROUND: To examine the association between pregnant women with rheumatoid arthritis (RA) and the risk of preeclampsia. METHODS: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) under the number CRD42022361571. The primary outcome was preeclampsia. Two evaluators independently reviewed the included studies, assessed their risk of bias, and extracted the data. Unadjusted and adjusted ratios with 95% confidence intervals and 95% prediction intervals were calculated. Heterogeneity was quantified using the І2 statistic, where І2 ≥ 50% indicated the presence of significant heterogeneity. Subgroup and sensitivity analyses were performed to test the robustness of the overall findings. RESULTS: A total of 8 studies, including 10,951,184 pregnant women, of whom 13,333 were diagnosed with RA, met the inclusion criteria. Meta-analysis revealed that pregnant women with RA were significantly more likely to develop preeclampsia than those without RA (pooled odds ratio, 1.66; 95% confidence interval, 1.52-1.80; P < .001; І2 < .001). CONCLUSION: RA during pregnancy is associated with higher odds of preeclampsia.

Pre- and Post-Pandemic (COVID-19) Mental Health of International Students: Data from a Longitudinal Study.

Purpose: International students are highly vulnerable to the risk of mental health worsening before and during the pandemic (COVID-19). This study investigated international students' mental health pre- and post-pandemic (COVID-19). Methods: It is a longitudinal study, and data were collected online, pre-pandemic (N = 470) and during the pandemic (N = 420). Using a random sampling technique, a self-administered questionnaire was used to measure mental health, including depression and anxiety. Results: Findings show that international students' mental health was good in pre-pandemic. Meanwhile, international students were found to be more depressed and anxious during the pandemic. Findings also investigated that in the pre-pandemic phase, young students' and mainly females' mental health was worsened. Conclusion: This study concluded that students' mental problems are alarming, so the university should provide psychological services for the student's mental health. Post-pandemic is leaving long-lasting psychological effects and will require further investigation.

Digital Rehabilitation Programs Improve Therapeutic Exercise Adherence for Patients With Musculoskeletal Conditions: A Systematic Review With Meta-Analysis.

OBJECTIVE: To investigate the effects of digital rehabilitation for improving adherence to therapeutic exercise in people with musculoskeletal conditions. DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: Five databases were searched from their inception to March 2022. STUDY SELECTION CRITERIA: We included randomized controlled trials evaluating digital rehabilitation programs to improve adherence to therapeutic exercise for people with musculoskeletal conditions. DATA SYNTHESIS: We calculated standardized mean differences (SMDs) or mean differences (MDs) and 95% confidence intervals (CIs). Certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Bias was assessed using the Cochrane risk of bias tool. RESULTS: Eleven trials were included in the meta-analysis (n = 1144 participants). At short-term follow-up, digital rehabilitation was no better than nondigital rehabilitation (3 trials, adherence rate of prescribed exercise test SMD 0.50, 95% CI: -0.13, 1.13; 2 trials, self-reported exercise adherence test MD 1.07, 95% CI: 0.58, 1.56; 2 trials, assessor-reported exercise adherence test SMD -0.10, 95% CI: -0.56, 0.36). At intermediate-term follow-up, digital rehabilitation improved exercise adherence compared with nondigital rehabilitation (6 trials, adherence rate of prescribed exercise test SMD 0.53, 95% CI: 0.35, 0.70; 2 trials, self-reported exercise adherence test MD 1.50, 95% CI: 0.76, 2.25; 2 trials, Exercise Adherence Rating Scale test MD 5.86, 95% CI: 0.08, 11.65). At long-term follow-up, there was no clinically important difference between digital and nondigital rehabilitation (2 trials, adherence rate of prescribed exercise test SMD 0.28, 95% CI: -0.14, 0.70; 1 trial, self-reported exercise adherence test MD 0.20, 95% CI: -0.91, 1.31). CONCLUSION: Digital rehabilitation was effective at improving therapeutic exercise adherence in musculoskeletal conditions at mid-term follow-up, but not at short- and long-term follow-up. J Orthop Sports Phys Ther 2022;52(11):726-739. Epub: 12 August 2022. doi:10.2519/jospt.2022.11384.

The prognostic role of 18F-FDG PET/CT baseline quantitative metabolic parameters in peripheral T-cell lymphoma.

Objectives: The aim of this study is to investigate the prognostic significance of baseline maximum standard uptake value (SUVmax), whole body SUVmax (WBSUVmax), whole body metabolic tumor volume (WBMTV) and whole body total lesion glycolysis (WBTLG) in patients with peripheral T-cell lymphoma (PTCL). Methods: Eighty patients with PTCL who underwent pretreatment 18F-PET/CT were enrolled in this study. WBMTV and WBTLG were computed by using the margin threshold of SUV>3.0. WBSUVmax was obtained by summing of SUVmax of the whole-body SUVmax of 11 nodal and 10 extra-nodal lesions. Results: Median SUVmax was 13.8 (range, 4.6-35.5), median WBSUVmax was 24.6 (range, 4.6-153.4), median WBMTV was 149 cm3 (range, 4-4545 cm3) and median WBTLG was 1017 (range, 16.5-23739). Six patients with anaplastic large cell lymphoma, ALK positive were excluded in the following statistical analysis for their unique pathological types and good prognosis. The receiver operating curve (ROC) analysis showed that the optimal cut-off values of WBSUVmax, WBMTV and WBTLG with overall survival (OS) were 22.2, 169.5 cm3 and 746.1, respectively. Patients with high WBSUVmax, WBMTV and WBTLG had a poor prognosis. WBSUVmax, WBMTV and WBTLG were associated with international prognostic index (IPI) and prognostic index for T-cell lymphoma (PIT). In multivariate analysis, WBTLG and PIT were independent prognostic factors of both progression free survival (PFS) and OS. Conclusions: Our study shows that high WBTLG, WBMTV and WBSUVmax could predict a relatively poor prognosis, and has a highly significant association with PIT and IPI.WBTLG could be an independent predictive factor for survival outcomes in patients with PTCL.

Regulatory Effect of General Anesthetics on Activity of Potassium Channels / 神经科学通报·英文版

General anesthesia is an unconscious state induced by anesthetics for surgery. The molecular targets and cellular mechanisms of general anesthetics in the mammalian nervous system have been investigated during past decades. In recent years, K channels have been identified as important targets of both volatile and intravenous anesthetics. This review covers achievements that have been made both on the regulatory effect of general anesthetics on the activity of K channels and their underlying mechanisms. Advances in research on the modulation of K channels by general anesthetics are summarized and categorized according to four large K channel families based on their amino-acid sequence homology. In addition, research achievements on the roles of K channels in general anesthesia in vivo, especially with regard to studies using mice with K channel knockout, are particularly emphasized.

Prognostic value of whole-body SUVmax of nodal and extra-nodal lesions detected by 18F-FDG PET/CT in extra-nodal NK/T-cell lymphoma.

We analyzed data from 54 newly-diagnosed persons with extra-nodal natural killer/T-cell (NK/T) lymphoma, who had a pretreatment 18F-FDG PET/CT study, to determine whether the sum of SUVmax of all the nodal and extra-nodal lesions predicted progression-free survival (PFS) and/or overall survival (OS). Three models (WB1SUVmax, WB2SUVmax, WB3SUVmax) based on the basis of the sum of SUVmax of the whole-body SUVmax of 11 nodal and 10 extra-nodal lesions were tested. The discrimination value of these models was evaluated using time-dependent receiver-operator characteristic (ROC) curves and corresponding areas under the curve (AUC) in training and validation cohorts. Findings were validated in an independent cohort of 15 subjects. ROC curve analysis showed the optimal cut-off values for WB1SUVmax, WB2SUVmax and WB3SUVmax were 15.8 (sensitivity 92%, specificity 67%, AUC 0.811; P<0.001), 12.7 (sensitivity 96%; specificity 57%; AUC 0.785; P<0.001) and 15.8 (sensitivity 88%; specificity 70%; AUC 0.793; P<0.001). Multivariate analyses indicated WB3SUVmax was independently associated with PFS (hazard ratio [HR]=3.67, 95% confidence interval [95% CI]=1.19, 11.29; P=0.023) and OS (HR= 4.51 [1.02, 19.91]; P=0.047). WB3SUVmax calculated based of the sum of the SUVmax of 3 nodal and 10 extra-nodal lesions was significantly associated with PFS and OS.

[Long-fragment RNA inhibits hepatitis B virus gene replication and expression in HepG2.2.15 cells].

To evaluate the inhibitory effects of long antisense RNA on HBV replication in HepG2.2.15 cells. The coding region of HBV S gene was cloned into pTARGET vector in sense and antisense orientations and the recombinant plasmids were transfected into HepG2.2.15 cells which were divided into HBS2 (antisense RNA) group, HBS4 (sense RNA) group and control group. HBsAg and HBeAg in the culture supernate were detected by ELISA. The HBV DNA in the supernate was quantified by real-time PCR. After treatment, the levels of HBsAg in HepG2.2.15 cell supernatants of three groups were 0.621+/-0.027, 3.399+/-0.018 and 2.232+/-0.187 respectively; the levels of HBeAg were 0.749+/-0.019, 1.548+/-0.025 and 1.570+/-0.044 respectively and the levels of HBV DNA were 1.597+/-0.082, 3.381+/-0.297 and 3.610+/-0.063 respectively. The expressions of HBsAg and HBeAg and the HBV DNA level in HBS2 group were remarkably reduced as compared to the control (Z = -2.309, P value is less than 0.05); whereas the sense plasmid transfection (HBS4) did not affect HBeAg (Z = -0.866) and HBV DNA (Z = -1.155) levels in the culture supernate but slightly increased the HBsAg level (Z = -2.309). Antisense RNA might be a useful tool to repress HBV replication.

Liquid chromatographic/mass spectrometric assay of rabeprazole in dog plasma for a pharmacokinetic study.

In order to evaluate the pharmacokinetic (PK) profile of rabeprazole (RA) sterile powder for injection, a rapid, sensitive and specific assay for quantitative determination of RA in dog plasma was developed and validated. After a liquid-liquid extraction procedure, samples were analyzed by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) using omepazole as the internal standard (IS). The analyte and IS was chromatographed on a ZORBAX Extend-C(18) analytical column (50 x 2 mm i.d, 5 microm, Agilent Technologies, USA). The assay was linear in the range 1-2000 ng/mL. The lower limit of quantification of RA was 1 ng/mL. The recovery of RA was greater than 70%. The within- and between-batch accuracy was 102.7-107.4% and 103.5-105.7%, respectively. The plasma samples for the PK study were collected at defined time points during and after an intravenous injection (1 mg/kg) to beagle dogs and analyzed by LC-ESI-MS method. The PK parameters, such as half-life, volume of distribution, total clearance and elimination rate constant, were determined. The PK profile of RA gave insights into the application in the clinics.

Sensitive and selective liquid chromatography-electrospray ionization mass spectrometry analysis of ginkgolide B in dog plasma.

As an important active constituent of Ginkgo biloba extract, ginkoglide B is a highly selective and competitive PAF receptor antagonist which has been widely used in clinical applications. A novel high-performance liquid chromatography-electrospray ionization mass spectromentry (LC-ESI-MS) method was developed for the determination of ginkgolide B in dog plasma. After liquid/liquid extraction with ether and high-performance liquid chromatography (HPLC) gradient separation with 0.01% of ammonia water (v/v)-methanol as the mobile phase, the deprotonized anions [M-H](-1) at m/z 423 of ginkoglide B, and [M-H](-1) at m/z 492 of internal standard (IS) glibenclamide were analyzed by LC-ESI-MS in selected ion monitoring (SIM) mode. Chromatographic separation was achieved in less than 9 min and calibration curve was linear over a concentration range of 0.1-20 ng/ml. The described assay method was successfully applied to the pre-clinical pharmacokinetic study of ginkoglide B. After intragastric administration of ginkgolide B to beagle dogs, C(max) and T(max) of ginkgolide B were 43.8 +/- 6.24 ng/ml and 0.5 h, respectively, and the elimination half-life (t(1/2)) was 2.85 +/- 0.54 h.