Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis in Drosophila.

De novo lipogenesis is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged during Drosophila larval development from the second to the third instar larval stages (L2 to L3) when lipogenesis is hyperactive. Instead, acetylation of FASN is significantly upregulated in fast-growing larvae. We further show that lysine K813 residue is highly acetylated in developing larvae, and its acetylation is required for elevated FASN activity, body fat accumulation, and normal development. Intriguingly, K813 is autoacetylated by acetyl-CoA (AcCoA) in a dosage-dependent manner independent of acetyltransferases. Mechanistically, the autoacetylation of K813 is mediated by a novel P-loop-like motif (N-xx-G-x-A). Lastly, we find that K813 is deacetylated by Sirt1, which brings FASN activity to baseline level. In summary, this work uncovers a previously unappreciated role of FASN acetylation in developmental lipogenesis and a novel mechanism for protein autoacetylation, through which Drosophila larvae control metabolic homeostasis by linking AcCoA, lysine acetylation, and de novo lipogenesis.

MiR-150-5p Alleviates Renal Tubule Epithelial Cell Fibrosis via the Inhibition of Epithelial-Mesenchymal Transition by Targeting ZEB1.

INTRODUCTION: Although microRNA (miR)-150-5p participates in the progression of renal fibrosis, its mechanism of action remains elusive. METHODS: A mouse model of unilateral ureteral obstruction was used. The in vitro renal fibrosis model was established by stimulating human kidney 2 (HK-2) cells with transforming growth factor beta 1 (TGF-ß1). The expression profiles of miR-150-5p, zinc finger E-box binding homeobox 1 (ZEB1), and other fibrosis- and epithelial-mesenchymal transition (EMT)-linked proteins were determined using Western blot and quantitative reverse transcription polymerase chain reaction. The relationship between miR-150-5p and ZEB1 in HK-2 cells was confirmed by a dual-luciferase reporter assay. RESULTS: Both in vivo and in vitro renal fibrosis models revealed reduced miR-150-5p expression and elevated ZEB1 level. A significant decrease in E-cadherin levels, as well as increases in alpha smooth muscle actin (α-SMA) and collagen type I (Col-I) levels, was seen in TGF-ß1-treated HK-2 cells. The overexpression of miR-150-5p ameliorated TGF-ß1-mediated fibrosis and EMT. Notably, miR-150-5p acts by directly targeting ZEB1. A significant reversal of the inhibitory impact of miR-150-5p on TGF-ß1-mediated fibrosis and EMT in HK-2 cells was observed upon ZEB1 overexpression. CONCLUSION: MiR-150-5p suppresses TGF-ß1-induced fibrosis and EMT by targeting ZEB1 in HK-2 cells, providing helpful insights into the therapeutic intervention of renal fibrosis.

A Very Deep Graph Convolutional Network for 13C NMR Chemical Shift Calculations with Density Functional Theory Level Performance for Structure Assignment.

Nuclear magnetic resonance (NMR) chemical shift calculations are powerful tools for structure elucidation and have been extensively employed in both natural product and synthetic chemistry. However, density functional theory (DFT) NMR chemical shift calculations are usually time-consuming, while fast data-driven methods often lack reliability, making it challenging to apply them to computationally intensive tasks with a high requirement on quality. Herein, we have constructed a 54-layer-deep graph convolutional network for 13C NMR chemical shift calculations, which achieved high accuracy with low time-cost and performed competitively with DFT NMR chemical shift calculations on structure assignment benchmarks. Our model utilizes a semiempirical method, GFN2-xTB, and is compatible with a broad variety of organic systems, including those composed of hundreds of atoms or elements ranging from H to Rn. We used this model to resolve the controversial J/K ring junction problem of maitotoxin, which is the largest whole molecule assigned by NMR calculations to date. This model has been developed into user-friendly software, providing a useful tool for routine rapid structure validation and assignation as well as a new approach to elucidate the large structures that were previously unsuitable for NMR calculations.

Screening of candidate genes related to differences in growth and development between Chinese indigenous and Western pig breeds.

Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.

A long-acting recombinant FSH supports high-quality mouse follicle development and oocyte maturation in vitro by coordinating somatic and germ cell transcriptomes.

Strategies to maximize individual fertility chances are constant requirements of ART. In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli. In this study, a new type of recombinant FSH (KN015) with a prolonged half-life is proposed as an alternative to canonical FSH. KN015 supports the in vitro development of mouse follicles from primary to preovulatory stage with higher efficiency than canonical FSH and enhanced post-fertilization development rates of the ovulated oocytes. The use of KN015 also allows us to compare the dynamic transcriptome changes in oocytes and granulosa cells at different stages, in vivo and in vitro. In particular, KN015 facilitates mRNA accumulation in growing mouse oocytes and prevents spontaneous luteinization of granulosa cells in vitro. Novel analyses of transcriptome changes in this study reveal that the in vivo oocytes were more efficient than in vitro oocytes in terms of maternal mRNA clearing during meiotic maturation. KN015 promotes the degradation of maternal mRNA during in vitro oocyte maturation, improves cytoplasmic maturation and, therefore, enhances embryonic developmental potential. These findings establish new transcriptome data for oocyte and granulosa cells at the key stages of follicle development, and should help to widen the use of KN015 as a valid and commercially available hormonal support enabling optimized in vitro development of follicles and oocytes.

CA916798 predicts poor prognosis and promotes Gefitinib resistance for lung adenocarcinoma.

BACKGROUND: Our previous studies have identified CA916798 as a chemotherapy resistance-associated gene in lung cancer. However, the histopathological relevance and biological function of CA916798 in lung adenocarcinoma (LUAD) remains to be delineated. In this study, we further investigated and explored the clinical and biological significance of CA916798 in LUAD. METHODS: The relationship between CA916798 and clinical features of LUAD was analyzed by tissue array and online database. CCK8 and flow cytometry were used to measure cell proliferation and cell cycle of LUAD after knockdown of CA916798 gene. qRT-PCR and western blotting were used to detect the changes of cell cycle-related genes after knockdown or overexpression of CA916798. The tumorigenesis of LUAD cells was evaluated with or without engineering manipulation of CA916798 gene expression. Response to Gefitinib was evaluated using LUAD cells with forced expression or knockdown of CA916798. RESULTS: The analysis on LUAD samples showed that high expression of CA916798 was tightly correlated with pathological progression and poor prognosis of LUAD patients. A critical methylation site in promoter region of CA916798 gene was identified to be related with CA916798 gene expression. Forced expression of CA916798 relieved the inhibitory effects of WEE1 on CDK1 and facilitated cell cycle progression from G2 phase to M phase. However, knockdown of CA916798 enhanced WEE1 function and resulted in G2/M phase arrest. Consistently, chemical suppression of CDK1 dramatically inhibited G2/M phase transition in LUAD cells with high expression of CA916798. Finally, we found that CA916798 was highly expressed in Gefitinib-resistant LUAD cells. Exogenous expression of CA916798 was sufficient to endow Gefitinib resistance with tumor cells, but interference of CA916798 expression largely rescued response of tumor cells to Gefitinib. CONCLUSIONS: CA916798 played oncogenic roles and was correlated with the development of Gefitinib resistance in LUAD cells. Therefore, CA916798 could be considered as a promising prognostic marker and a therapeutic target for LUAD.

The impact of climate change and human activities to vegetation carbon sequestration variation in Sichuan and Chongqing.

Exploring the vegetation carbon cycle and the factors influencing vegetation carbon sequestration in areas with complex plateau-basin topography and fragile ecosystems is crucial. In this study, spatial and temporal characteristics of carbon sequestration by vegetation in Sichuan and Chongqing from 2010 to 2020 and the influencing factors were investigated through simulations of net primary productivity (NPP) using the modified Carnegie-Ames-Stanford approach (CASA) and the Thornthwaite Memorial (TM) model and using chemical equations of photochemical reactions. The results indicated that: The spatial distribution of carbon sequestration capacity (CSC) trends showed an increase in the east (the most prominent increased trend along the mountainous areas of the basin) and a decrease in the west (western Sichuan plateau). Differences exist in the impact factors of CSC in different regions. In the basin margins and mountainous areas, where the proportion of forests was high, a combination of climate change and human activities contributed to the increase in CSC. The relatively warm and humid meteorological conditions in the hinterland of the basin were more conducive to the increase in CSC, and climate change also affected the region more significantly. In contrast, in the relatively high altitude of western Sichuan, controlled human activities were the key to improving CSC. The results of the study contribute to the understanding of the basic theory of vegetation carbon cycle in areas with complex plateau-basin topography and fragile ecosystems, as well as to provide suggestions for ecological shelter construction and ecological restoration in the upper Yangtze River.

Intrinsically disordered protein RBM14 plays a role in generation of RNA:DNA hybrids at double-strand break sites.

Accumulating evidence suggests participation of RNA-binding proteins with intrinsically disordered domains (IDPs) in the DNA damage response (DDR). These IDPs form liquid compartments at DNA damage sites in a poly(ADP ribose) (PAR)-dependent manner. However, it is greatly unknown how the IDPs are involved in DDR. We have shown previously that one of the IDPs RBM14 is required for the canonical nonhomologous end joining (cNHEJ). Here we show that RBM14 is recruited to DNA damage sites in a PARP- and RNA polymerase II (RNAPII)-dependent manner. Both KU and RBM14 are required for RNAPII-dependent generation of RNA:DNA hybrids at DNA damage sites. In fact, RBM14 binds to RNA:DNA hybrids. Furthermore, RNA:DNA hybrids and RNAPII are detected at gene-coding as well as at intergenic areas when double-strand breaks (DSBs) are induced. We propose that the cNHEJ pathway utilizes damage-induced transcription and intrinsically disordered protein RBM14 for efficient repair of DSBs.

A new abietane diterpenoid from Lycopodium complanatum.

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].

Maternal Exercise Prior to and during Gestation Induces Sex-Specific Alterations in the Mouse Placenta.

While exercise (EX) during pregnancy is beneficial for both mother and child, little is known about the mechanisms by which maternal exercise mediates changes in utero. Six-week-old female C57BL/6 mice were divided into two groups: with (exercise, EX; N = 7) or without (sedentary, SED; N = 8) access to voluntary running wheels. EX was provided via 24 h access to wheels for 10 weeks prior to conception until late pregnancy (18.5 days post coitum). Sex-stratified placentas and fetal livers were collected. Microarray analysis of SED and EX placentas revealed that EX affected gene transcript expression of 283 and 661 transcripts in male and female placentas, respectively (±1.4-fold, p < 0.05). Gene Set Enrichment and Ingenuity Pathway Analyses of male placentas showed that EX led to inhibition of signaling pathways, biological functions, and down-regulation of transcripts related to lipid and steroid metabolism, while EX in female placentas led to activation of pathways, biological functions, and gene expression related to muscle growth, brain, vascular development, and growth factors. Overall, our results suggest that the effects of maternal EX on the placenta and presumably on the offspring are sexually dimorphic.

Which anthropometric measurement is better for predicting survival of patients with cancer cachexia?

No relevant studies have yet been conducted to explore which measurement can best predict the survival time of patients with cancer cachexia. This study aimed to identify an anthropometric measurement that could predict the 1-year survival of patients with cancer cachexia. We conducted a nested case-control study using data from a multicentre clinical investigation of cancer from 2013 to 2020. Cachexia was defined using the Fearon criteria. A total of 262 patients who survived less than 1 year and 262 patients who survived more than 1 year were included in this study. Six candidate variables were selected based on clinical experience and previous studies. Five variables, BMI, mid-arm circumference, mid-arm muscle circumference, calf circumference and triceps skin fold (TSF), were selected for inclusion in the multivariable model. In the conditional logistic regression analysis, TSF (P = 0·014) was identified as a significant independent protective factor. A similar result was observed in all patients with cancer cachexia (n 3084). In addition, a significantly stronger positive association between TSF and the 1-year survival of patients with cancer cachexia was observed in participants aged > 65 years (OR: 0·94; 95 % CI 0·89, 0·99) than in those aged ≤ 65 years (OR: 0·96; 95 % CI 0·93, 0·99; Pinteraction = 0·013) and in participants with no chronic disease (OR: 0·92; 95 % CI 0·87, 0·97) than in those with chronic disease (OR: 0·97; 95 % CI 0·94, 1·00; Pinteraction = 0·049). According to this study, TSF might be a good anthropometric measurement for predicting 1-year survival in patients with cancer cachexia.

The prognostic effect of hemoglobin on patients with cancer cachexia: a multicenter retrospective cohort study.

OBJECTIVES: To clarify the influence of hemoglobin on cancer cachexia and to determine whether hemoglobin affects the prognosis or quality of life of patients with cancer cachexia and whether these effects are caused by an interaction between hemoglobin and other factors. MATERIAL AND METHODS: This study was a multicenter cohort of 2715 patients with cancer cachexia diagnosed from June 2012 to December 2019. The primary outcomes and measures were overall survival (OS) time and all-cause mortality. The association between hemoglobin and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided p-value. Optimal stratification was used to determine the threshold value. We also evaluated the cross-classification of hemoglobin and each variable with survival. RESULTS: Among the 2715 participants diagnosed with cancer cachexia, 1592 (58.6%) were male, and the mean (SD) age was 58.8 (11.7) years. The optimal cutoff point for hemoglobin as a predictor of cancer cachexia mortality was 140 g/L for males and 101 g/L for females in our research. The decrease in hemoglobin was positively correlated with all-cause mortality. These associations were consistent across cancer subtypes. In the multivariable analysis, after adjusting for sex, age, TNM stage, tumor type, radiotherapy, chemotherapy, Karnofsky performance status score, and other factors, patients diagnosed with cancer cachexia who had low hemoglobin levels were more likely to have a worse prognosis (HR 2.40; 95% CI, 1.12-1.51). CONCLUSION: Our results suggested that the proposed hemoglobin cutoff point would be valuable for prognostic prediction in patients with cancer cachexia, especially for long-term prognosis.

A robust CRISPR-Cas9-based fluorescent reporter assay for the detection and quantification of DNA double-strand break repair.

DNA double-strand breaks (DSBs) are highly cytotoxic lesions that can lead to chromosome rearrangements, genomic instability and cell death. Consequently, cells have evolved multiple mechanisms to efficiently repair DSBs to preserve genomic integrity. We have developed a DSB repair assay system, designated CDDR (CRISPR-Cas9-based Dual-fluorescent DSB Repair), that enables the detection and quantification of DSB repair outcomes in mammalian cells with high precision. CDDR is based on the introduction and subsequent resolution of one or two DSB(s) in an intrachromosomal fluorescent reporter following the expression of Cas9 and sgRNAs targeting the reporter. CDDR can discriminate between high-fidelity (HF) and error-prone non-homologous end-joining (NHEJ), as well as between proximal and distal NHEJ repair. Furthermore, CDDR can detect homology-directed repair (HDR) with high sensitivity. Using CDDR, we found HF-NHEJ to be strictly dependent on DNA Ligase IV, XRCC4 and XLF, members of the canonical branch of NHEJ pathway (c-NHEJ). Loss of these genes also stimulated HDR, and promoted error-prone distal end-joining. Deletion of the DNA repair kinase ATM, on the other hand, stimulated HF-NHEJ and suppressed HDR. These findings demonstrate the utility of CDDR in characterizing the effect of repair factors and in elucidating the balance between competing DSB repair pathways.

Knockdown of circHECTD1 inhibits oxygen-glucose deprivation and reperfusion induced endothelial-mesenchymal transition.

Ischemic stroke (IS) has become a cerebrovascular disease which seriously threatens the elderly people. It has been reported that circRNAs participate in multiple diseases, including IS. However, the role of circHECTD1 in IS remains largely unknown. To mimic IS in vitro, human cerebral microvascular endothelial cells (HCMECs) were treated with oxygen glucose deprivation/reperfusion (OGD/R). Meanwhile, MCAO mouse model was established to detect the expression of circHECTD1 in IS. qRT-PCR and western blot were used to test gene and protein expressions, respectively. CCK-8 assay was used to investigate the cell viability. Moreover, cell migration and tube formation were assessed by transwell and tube formation assays. In addition, RIP and luciferase assay were performed to explore the association among circHECTD1, miR-335 and NOTCH2. CircHECTD1 was significantly upregulated in IS. OGD/R significantly induced EndoMT in HCMECs, while knockdown of circHECTD1 notably reversed this phenomenon. In addition, silencing of circHECTD1 remarkably reversed OGD/R-induced promotion of HCMEC tube formation and migration. Meanwhile, circHECTD1 upregulated the level of NOTCH2 through binding with miR-335. Furthermore, miR-335 inhibited the process of EndoMT in IS via targeting NOTCH2. In summary, circHECTD1 knockdown significantly alleviated EndoMT process in HCMECs via mediation of miR-335/NOTCH2 axis. Thus, circHECTD1 might act as a potential target against IS.

C-Reactive Protein-to-Albumin Ratio as an Early Biomarker to Identify Sepsis in Neonates with Pneumonia.

Objectives: Neonates with pneumonia often also have sepsis, and the identifying sepsis from pneumonia may be a challenge for clinicians. However, there are no available data regarding the clinical value C-reactive protein-to-albumin ratio (CAR) in identifying sepsis in neonates with pneumonia. The aim of this study was to evaluate the clinical value of CAR in identifying sepsis in neonates with pneumonia. Methods: 847 neonates with pneumonia were included in this study, of which 511 neonates were diagnosed with sepsis. Neonates were divided into the sepsis group and the nonsepsis group. All neonates underwent extensive and necessary clinical and laboratory tests. CAR was calculated as serum C-reactive protein (ng/ml)/albumin (mg/ml). All statistical analyses were performed using the statistical package SPSS 24.0, as appropriate. Results: Compared with the nonsepsis group, neonates with sepsis have a higher CAR (P < 0.001). Further analysis showed that the prevalence of neonates with sepsis increased significantly from 41.0% in the low CAR group (CAR ≤ 0.024 × 10-3) to 80.0% in the high CAR group (CAR > 0.024 × 10-3) (P < 0.001). Correlation analysis showed that there was a strong positive correlation between CAR and PCT (r = 0.452, P < 0.001), nSOFA (r = 0.267, P < 0.001), and the prolonged length of hospital stay (r = 0.311, P < 0.001). Multiple logistic regression showed that CAR was an independent risk factor for the presence of sepsis in neonates with pneumonia. Receiver operating characteristic curve analysis revealed that CAR had adequate discriminatory power in predicting sepsis in neonates with pneumonia (area under curve (AUC) = 0.76, 95% CI 0.73-0.79, P < 0.001). Conclusions: CAR can be used as a new marker to identify sepsis in neonates with pneumonia.

Two New C21 Steroidal Glycosides from Selaginella Braunii Baker.

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.

Invisible Gateway by Superscattering Effect of Metamaterials.

Illusion devices, such as superscatterer and invisible gateway, have been theoretically studied under the theory of transformation optics and folded geometry transformations. The realization of these devices needs building blocks of metamaterials with negative permittivities and permeabilities. However, superscattering effects, such as stopping wave propagation in an air channel, have not been verified from illusion devices physically because of the challenge of metamaterial design, fabrication, and material loss. In this Letter, we implement a big metamaterial superscatterer, and experimentally demonstrate its superscattering effect at microwave frequencies by field-mapping technology. We confirm that superscattering is originated from the excitation of surface plasmons. Integrated with superscatterer, we experimentally display that an invisible gateway could stop electromagnetic waves in an air channel with a width much larger than the cutoff width of the corresponding rectangular waveguide. Our results provide a first direct observation of superscattering effect of double negative metamaterials and invisible gateway for electromagnetic waves. It builds up an ideal platform for future designs of other illusion devices.

Cation-exchange synthesis of PbSe/ZnSe hetero-nanobelts with enhanced near-infrared photoelectronic performance.

To develop excellent photoelectronic and photovoltaic devices, a semiconductor with high photoelectron production efficiency and broad band absorption is urgently required. In this article, novel II-type PbSe/ZnSe hetero-nanobelts with enhanced near-infrared absorption have been synthesized via a facile strategy of a partial cation-exchange reaction and thermal treatment. Derived from ZnSe·0.5N2H4nanobelts as templates, the belt-like morphology was preserved. Due to the mismatch of the crystal type and parameters between PbSe and ZnSe, the formed PbSe in the form of nanoparticles were separated out and decorated on the nanobelts. Furthermore, the composition ratio of Pb/Zn can be tuned through manipulating the adding amount of Pb2+cations, the reaction temperature and time. The ultraviolet-visible-infrared diffuse spectra measurements suggest that the as-prepared PbSe/ZnSe hetero-nanobelts exhibited a broad band absorption from 300 to 1000 nm. In addition, they demonstrated excellent photoresponsivity in the same wavelength region and displayed a peak at approximately 840 nm. Finally, the enhanced photoelectronic sensing mechanism was discussed.

Identification of a new natural biflavonoids against breast cancer cells induced ferroptosis via the mitochondrial pathway.

Breast cancer is one of the major malignant tumors in females, and currently, recurrence and metastasis are the main obstacles preventing effective breast cancer treatment. Biflavonoids of secondary metabolites from plants are excellent anticancer agents to fight sensitive and resistant breast cancer cell lines. In this study, six C-3'-C-6″ biflavonoids, including one new robustaflavone A (1, RF-A) and five known robustaflavone derivatives (2-6), were isolated from Selaginella trichoclada for the first time. We aimed to evaluate the inhibitory effects of compounds 1-6 against human breast cancer MCF-7 cells. Among the six compounds, RF-A showed the strongest activity, decreasing cell viability with an IC50 value of 11.89 µΜ. Furthermore, RF-A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways.

Effect of Internet-Based Rehabilitation Programs on Improvement of Pain and Physical Function in Patients with Knee Osteoarthritis: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Osteoarthritis (OA) is a chronic, debilitating, and degenerative joint disease. However, it is difficult for patients with knee OA to access conventional rehabilitation when discharging from the hospital. Internet-based rehabilitation is one of the promising telemedicine strategies to provide a means combining monitoring, guidance, and treatment for patients with knee OA. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis for assessing the effect of internet-based rehabilitation programs on pain and physical function in patients with knee OA. METHODS: Keywords related to knee OA and internet-based rehabilitation were systematically searched in the Web of Science, MEDLINE, EMBASE, CENTRAL, Scopus, PEDro (Physiotherapy Evidence Database), CNKI, SinoMed, and WANFANG databases from January 2000 to April 2020. Only randomized controlled trials were included. The authors independently screened the literature. The main outcome measures were focused on pain and physical function. A meta-analysis was performed on the collected data. Review Manager (RevMan, version 5.3) was used for all analyses. RESULTS: The systematic review identified 6 randomized controlled trials, 4 of which were included in the meta-analysis, comprising a total of 791 patients with knee OA. The meta-analysis with the fixed-effects model showed that the internet-based rehabilitation programs could significantly alleviate the osteoarthritic pain for patients compared with conventional rehabilitation (standardized mean difference [SMD] -0.21, 95% CI -0.4 to -0.01, P=.04). No significant difference was found in the improvement of physical function in patients with knee OA compared with conventional rehabilitation within 2 to 12 months (SMD -0.08, 95% CI -0.27 to 0.12, P=.43). CONCLUSIONS: This systematic review shows that internet-based rehabilitation programs could improve the pain but not physical function for patients with knee OA. However, there was a very small number of studies that could be included in the review and meta-analysis. Thus, further studies with large sample sizes are warranted to promote the effectiveness of internet-based rehabilitation and to develop its personalized design.