Combined gestational age and serum fucose for early prediction of risk for bronchopulmonary dysplasia in premature infants.

OBJECTIVE: As the predominant complication in preterm infants, Bronchopulmonary Dysplasia (BPD) necessitates accurate identification of infants at risk and expedited therapeutic interventions for an improved prognosis. This study evaluates the potential of Monosaccharide Composite (MC) enriched with environmental information from circulating glycans as a diagnostic biomarker for early-onset BPD, and, concurrently, appraises BPD risk in premature neonates. MATERIALS AND METHODS: The study incorporated 234 neonates of ≤32 weeks gestational age. Clinical data and serum samples, collected one week post-birth, were meticulously assessed. The quantification of serum-free monosaccharides and their degraded counterparts was accomplished via High-performance Liquid Chromatography (HPLC). Logistic regression analysis facilitated the construction of models for early BPD diagnosis. The diagnostic potential of various monosaccharides for BPD was determined using Receiver Operating Characteristic (ROC) curves, integrating clinical data for enhanced diagnostic precision, and evaluated by the Area Under the Curve (AUC). RESULTS: Among the 234 neonates deemed eligible, BPD development was noted in 68 (29.06%), with 70.59% mild (48/68) and 29.41% moderate-severe (20/68) cases. Multivariate analysis delineated several significant risk factors for BPD, including gestational age, birth weight, duration of both invasive mechanical and non-invasive ventilation, Patent Ductus Arteriosus (PDA), pregnancy-induced hypertension, and concentrations of two free monosaccharides (Glc-F and Man-F) and five degraded monosaccharides (Fuc-D, GalN-D, Glc-D, and Man-D). Notably, the concentrations of Glc-D and Fuc-D in the moderate-to-severe BPD group were significantly diminished relative to the mild BPD group. A potent predictive capability for BPD development was exhibited by the conjunction of gestational age and Fuc-D, with an AUC of 0.96. CONCLUSION: A predictive model harnessing the power of gestational age and Fuc-D demonstrates promising efficacy in foretelling BPD development with high sensitivity (95.0%) and specificity (94.81%), potentially enabling timely intervention and improved neonatal outcomes.

Comparison of the efficacy of Oxford unicondylar replacement for the treatment of spontaneous osteonecrosis of the knee versus medial knee osteoarthritis: a meta-analysis.

OBJECTIVE: Meta-analysis of the comparative efficacy of Oxford unicompartmental knee arthroplasty (OUKA) for the treatment of spontaneous osteonecrosis of the knee (SONK) and medial knee osteoarthritis (MKOA). METHODS: A computerized search was conducted for literature related to OUKA treatments of SONK and MKOA across various databases, including the China National Knowledge Infrastructure, WAN FANG, VIP, SinoMed, Cochrane Library, PubMed, Embase, and Web of Science, covering the period from each database's inception to September 2023. Literature screening, quality assessment and data extraction were performed according to the inclusion and exclusion criteria. After extracting the literature data, RevMan 5.4 software was applied to analyse the postoperative knee function score, postoperative knee mobility, postoperative pain, bearing dislocation rate, aseptic loosening, postoperative progression of posterolateral arthritis, and revision rate. RESULT: A total of 9 studies were included, including 6 cohort studies and 3 matched case‒control studies. A total of 1544 knees were included, including 183 in the SONK group and 1361 in the MKOA group. The meta-analysis results showed that the SONK and MKOA groups showed a significant difference in postoperative knee function scores [MD = 0.16, 95% CI (- 1.20, 1.51), P = 0.82], postoperative knee mobility [MD = - 0.05, 95% CI (- 1.99. 1.89), P = 0.96], postoperative pain [OR = 0.89, 95% CI (0.23, 3.45), P = 0.87], rate of bearing dislocation [OR = 1.28, 95% CI (0.34, 4.81), P = 0.71], aseptic loosening [OR = 2.22, 95% CI (0.56, 8.82), P = 0.26], postoperative posterolateral arthritis progression [OR = 2.14, 95% CI (0.47, 9.86), P = 0.33], and revision rate [OR = 1.28, 95% CI (0.53, 3.04), P = 0.58] were not statistically significant. CONCLUSION: OUKA treatment with SONK and MKOA can achieve similar satisfactory clinical results.

Design strategies and biological applications of ß-galactosidase fluorescent sensor in ovarian cancer research and beyond.

Beta-galactosidase (ß-galactosidase), a lysosomal hydrolytic enzyme, plays a critical role in the catalytic hydrolysis of glycosidic bonds, leading to the conversion of lactose into galactose. This hydrolytic enzyme is used as a biomarker in various applications, including enzyme-linked immunosorbent assays (ELISAs), gene expression studies, tuberculosis classification, and in situ hybridization. ß-Galactosidase abnormalities are linked to various diseases, such as ganglioside deposition, primary ovarian cancer, and cell senescence. Thus, effective detection of ß-galactosidase activity may aid disease diagnoses and treatment. Activatable optical probes with high sensitivity, specificity, and spatiotemporal resolution imaging capabilities have become powerful tools for visualization and real time tracking in vivo in the past decade. This manuscript reviews the sensing mechanism, molecular design strategies, and advances of fluorescence probes in the biological application of ß-galactosidase, particularly in the field of ovarian cancer research. Current challenges in tracking ß-galactosidase and future directions are also discussed.

Pathogenicity and host cytokines response of EqHV-8 infection in C57BL/6J mice.

Equid herpesvirus type 8 (EqHV-8) is known to cause abortion, respiratory signs, and viral encephalitis in equines. EqHV-8 has been reported to cause serious economic losses in large-scale donkey farms in China. However, little is known about the viral replication and immune reaction in the brains and lungs of EqHV-8-induced C57BL/6J mice. We determined the pathogenicity and immune status in a mice model. The C57BL/6J mice were infected with the EqHV-8 donkey/Shandong/10/2021 strain, and the clinical signs and body weights were evaluated every day. In addition, viremia, virus loads, and the expression of pro-inflammatory cytokines in mice brains and lungs were assessed at 1, 3, 5, and 7 days post infection (dpi). Our results demonstrated that mice in the EqHV-8 infected group displayed body weight loss, dyspnea signs, and viremia. The expression of interleukin (IL)-1ß, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 mRNA was increased in the brains and lungs of EqHV-8-infected mice than that in control group at 5 dpi and 7 dpi, and IL-12a expression was increased at 7 dpi. These data indicated that EqHV-8 elicited a strong cytokines response, caused neurogenic disease and respiratory signs in C57BL/6J mice, thus revealing the pathogenicity of EqHV-8.

Effects of PmaIAA27 and PmaARF15 genes on drought stress tolerance in pinus massoniana.

BACKGROUND: Auxin plays an important role in plant resistance to abiotic stress. The modulation of gene expression by Auxin response factors (ARFs) and the inhibition of auxin/indole-3-acetic acid (Aux/IAA) proteins play crucial regulatory roles in plant auxin signal transduction. However, whether the stress resistance of Masson pine (Pinus massoniana), as a representative pioneer species, is related to Aux/IAA and ARF genes has not been thoroughly studied and explored. RESULTS: The present study provides preliminary evidence for the regulatory role of the PmaIAA27 gene in abiotic stress response in Masson pine. We investigated the effects of drought and hormone treatments on Masson pine by examining the expression patterns of PmaIAA27 and PmaARF15 genes. Subsequently, we conducted gene cloning, functional testing using transgenic tobacco, and explored gene interactions. Exogenous auxin irrigation significantly downregulated the expression of PmaIAA27 while upregulating PmaARF15 in Masson pine seedlings. Moreover, transgenic tobacco with the PmaIAA27 gene exhibited a significant decrease in auxin content compared to control plants, accompanied by an increase in proline content - a known indicator of plant drought resistance. These findings suggest that overexpression of the PmaIAA27 gene may enhance drought resistance in Masson pine. To further investigate the interaction between PmaIAA27 and PmaARF15 genes, we performed bioinformatics analysis and yeast two-hybrid experiments which revealed interactions between PB1 structural region of PmaARF15 and PmaIAA27. CONCLUSION: The present study provides new insights into the regulatory functions of Aux/IAA and ARF genes in Masson pine. Overexpression of PmaIAA gene may have negative effects on the growth of Masson pine, but may improve the drought resistance. Therefore, this study has great application prospects.

Early diagnosis of renal pelvis villous adenoma: A case report.

BACKGROUND: Villous adenoma is a rare tumor in the urinary system that usually occurs in the bladder. It is extremely uncommon in the renal pelvis. Most of the previously reported cases have been diagnosed with severe hydronephrosis associated with renal parenchyma atrophy prior to surgery. Because of its rarity, available information on the pathogenesis, diagnosis, treatment and prognosis of the disease is limited. We reported a case of kidney stones with hydronephrosis. During percutaneous nephroscopic lithotripsy, a renal pelvis tumor was found. Biopsy confirmed that the tumor was a villous adenoma of the renal pelvis. CASE SUMMARY: A 68-year-old female was admitted to the hospital due to right kidney stones with right hydronephrosis. After admission, a urinary system plain computed tomography scan was performed, which revealed right kidney stones with right hydronephrosis and right upper ureteral dilatation. Multiple new cauliflower-like papillary masses were then discovered in the renal pelvis and calyces during right percutaneous nephroscopic lithotripsy. Biopsy results indicated villous adenoma with high-grade glandular intraepithelial neoplasia. The patient underwent laparoscopic radical resection of the right kidney and ureter. Based on histopathological and immunohistochemical examination, the patient was diagnosed with villous adenoma without adenocarcinoma. CONCLUSION: Villous adenoma is rare in the urinary system. We reported a case of renal pelvis villous adenoma, which may provide useful information for the early diagnosis and treatment of this tumor.

The m6A modulator-mediated cytarabine sensitivity and immune cell infiltration signature in acute myeloid leukemia.

PURPOSE: The study aims to investigate the impact of m6A modulators on drug resistance and the immune microenvironment in acute myeloid leukemia (AML). The emergence of drug resistance is a significant factor that contributes to relapse and refractory AML, leading to a poor prognosis. METHODS: The AML transcriptome data were retrieved from the TCGA database. The "oncoPredict" R package was utilized to assess the sensitivity of each sample to cytarabine (Ara-C) and classify them into distinct groups. Differential expression analysis was performed to identify m6A modulators differentially expressed between the two groups. Select Random Forest (RF) to build a predictive model. Model performance was evaluated using calibration curve, clinical decision curve, and clinical impact curve. The impacts of METTL3 on Ara-C sensitivity and immune microenvironment in AML were examined using GO, KEGG, CIBERSORT, and GSEA analyses. RESULTS: Seventeen out of 26 m6A modulators exhibited differential expression between the Ara-C-sensitive and resistant groups, with a high degree of correlation. We selected the 5 genes with the highest scores in the RF model to build a reliable and accurate prediction model. METTL3 plays a vital role in m6A modification, and further analysis shows its impact on the sensitivity of AML cells to Ara-C through its interaction with 7 types of immune-infiltrating cells and autophagy. CONCLUSION: This study utilizes m6A modulators to develop a prediction model for the sensitivity of AML patients to Ara-C, which can assist in treating AML drug resistance by targeting mRNA methylation.

Salinomycin sodium exerts anti diffuse large B-cell lymphoma activity through inhibition of LRP6-mediated Wnt/ß-catenin and mTORC1 signaling.

Low-density lipoprotein receptor-related protein-6 (LRP6) is overexpressed in various cancers. The small molecule salinomycin sodium inhibits LRP6. We observed a higher proportion of subjects with non-germinal center B (non-GCB) subtypes having high LRP6 expression than those with GCB subtypes by immunohistochemistry. The PCR and Western blot assays demonstrated increased LRP6 expression in non-GCB subtype cells. In addition, CCK-8 assays and transwell cell migration assays revealed that salinomycin sodium exhibited dose- and time-dependent inhibition of proliferation and migration in non-GCB subtype cells. Furthermore, Western blot assays showed that salinomycin sodium decreased the expression of Bcl2, while increasing the expression of Bax. Additionally, salinomycin sodium suppressed LRP6 expression, blocked LRP6 phosphorylation, and inhibited the Wnt/ß-catenin and mTORC1 signaling pathways. Our results suggest that LRP6 is highly expressed in non-GCB subtype. Furthermore, salinomycin sodium inhibited LRP6 expression and the Wnt/ß-catenin and mTORC1 signaling in non-GCB subtype cells, and displayed potent anticancer activity.

Accelerated Reinforcement of Calcareous sand via Biomineralization with Aluminum Ion Flocculant.

Microbially induced calcium carbonate precipitation (MICP) is an immensely growing technique that utilizes the metabolic pathways of bacteria to form calcite precipitation throughout the soil matrix, leading to improve geotechnical engineering properties. However, the excessive number of treatments limited the application of MICP for strengthening calcareous sand. To reduce the number of treatments and develop efficiencies, this paper investigates the optimized treatment protocol of adding aluminum ion flocculants to the cementing solution to accelerate the curing rate of the MICP and its effect. The results show that adding a certain concentration of AlCl3 to the cementing solution can resulted in a rapid increase in strength of the calcareous sand column. When 0.02 M aluminum chloride was added to the cementing solution, the unconfined compressive strength of the sand column reached 827 kPa after three treatments, and it reached 2 MPa after five treatments, while the control group needed to be treated 10 and 15 times, respectively, to reach equivalent strengths. In this paper, the unconfined compressive strength of the sand column formed using the proposed method was 27-40 times that of the control group at the same calcium carbonate content. The presented experimental approach can be used as a tool to design the treatment protocol for the engineering application of MICP-reinforced calcareous sand in practice.

Predictive Factors for Gleason Score Upgrading in Patients with Prostate Cancer after Radical Prostatectomy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Previous studies have revealed that Gleason score upgrading (GSU) was closely related to an increased biochemical recurrence rate and adverse oncologic outcomes in patients with prostate cancer (PC). Therefore, we performed a meta-analysis to determine the predictive factors for GSU following radical prostatectomy (RP). METHODS: We performed an extensive literature search using PubMed, Embase, and Cochrane in September 2022. In order to calculate the pooled odds ratio (OR), standardized mean difference (SMD), and 95% confidence intervals, a fixed effect or a DerSimonian and Laird random effect was applied. RESULTS: Twenty-six studies included 18,745 PC patients that were available for further analysis. Our results revealed that GSU was significantly correlated with age (summary SMD = 0.13; p = 0.004), prostate volume (PV) (summary SMD = -0.19;p < 0.001), preoperative PSA (p-PSA) (summary SMD = 0.18; p < 0.001), PSA density (PSAD) (summary SMD = 0.40; p < 0.001), number of positive cores (summary SMD = 0.28; p = 0.001), percentage of positive cores (summary SMD = 0.36; p < 0.001), Prostate Imaging Reporting and Data System (PI-RADS) scores (>3/≤3) (summary OR = 2.27; p = 0.001), clinical T stage (>T2/≤T2) (summary OR = 1.73; p < 0.001), positive surgical margins (PSM) (summary OR = 2.12; p < 0.001), extraprostatic extension (EPE) (summary OR = 2.73; p < 0.001), pathological T stage (>T2/≤T2) (summary OR = 3.45; p < 0.001), perineural invasion (PNI) (summary OR = 2.40; p = 0.008), and neutrophil to lymphocyte ratio (NLR) (summary SMD = 0.50; p < 0.001). However, we found that GSU was not significantly correlated with body mass index (BMI) (summary SMD = -0.02; p = 0.602). Moreover, our sensitivity and subgroup analyses showed that the findings were reliable. CONCLUSIONS: Age, PV, p-PSA, PSAD, number of positive cores, percentage of positive cores, PI-RADS score, clinical T stage, PSM, EPE, pathological T stage, PNI, and NLR are independent factors predicting GSU following RP. The findings may be helpful in risk stratification and personalized treatment in PC patients.

The antagonistic potential of peanut endophytic bacteria against Sclerotium rolfsii causing stem rot.

Peanut stem rot caused by Sclerotium rolfsii Sacc. is the most common disease of peanut worldwide and has become increasingly serious in recent years. This study is aimed at obtaining peanut endophytic bacteria with high antagonistic/protective effects against peanut stem rot. In total, 45 bacterial strains were isolated from healthy peanut plants from a severely impacted area. Of these, 6 exhibited antagonistic activity against S. rolfsii, including F-1 and R-11 with the most robust activity with an inhibition zone width of 20.25 and 15.49 mm, respectively. These two were identified as Bacillus sp. and Burkholderia sp., respectively, based on morphological, physiological, and biochemical characteristics and 16S rDNA sequencing. To the best of our knowledge, this is the first study to report the Burkholderia sp. antagonistic effect on S. rolfsii as a biological control agent for peanut stem rot. Their culture filtrates potently inhibited the hyphal growth, sclerotial formation, and germination of S. rolfsii. Also, the strain-produced volatile compounds inhibited the fungal growth. Pot experiments showed that F-1 and R-11 significantly reduced the peanut stem rot disease with the efficacy of 77.13 and 64.78%, respectively, which was significantly higher compared with carbendazim medicament (35.22%; P < 0.05). Meanwhile, F-1 and R-11 improved the activity of plant defense enzymes such as phenylalaninase (PAL), polyphenol oxidase (PPO), and peroxidase (POD) enhancing the systemic resistance of the peanut plants. This study demonstrated that Bacillus sp. F-1 and Burkholderia sp. R-11, with a strong antagonistic effect on S. rolfsii, can be potential biocontrol agents for peanut stem rot.

Preoperative nomogram predicting ventriculoperitoneal shunt longevity after initial shunt failure.

Background and objectives: Initial shunt failure following ventriculoperitoneal (VP) shunt surgery has a significant impact on the working time of the shunt. However, there are few studies regarding factors affecting VP shunt longevity. Hence, in this study, we aimed to build a nomogram to predict the longevity of the replacement VP shunt in patients with initial shunt failure. Methods: From 2011 to 2021, 142 patients with initial VP failure who underwent VP shunt revision were enrolled and relevant clinical and demographic factors were analyzed. Univariate and multivariate Cox proportional hazard regression models were used to choose predictors, and a nomogram was constructed using nine independent prognostic variables: sex, age, hydrocephalus type, intensive care unit admission, tracheostomy, decompressive craniectomy, craniotomy, lumbar cisterna drainage, and ventricular drainage. The prediction models' discrimination, accuracy, calibration, and clinical value were evaluated using Harrell's C-index, a calibration plot, and decision curve analysis. Results: At 1 month, 3 months, and 5 years, the nomogram's C-index was 0.680, 0.708, and 0.694, respectively. The nomogram's calibration plot provided a good fit for the overall prediction over the course of 1 year. Decision curve analysis predicted that 1-3 months after surgery will yield good net benefits between 30 and 50% probability thresholds. Conclusion: A preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement.

Sphingosine Kinase 1 Acts as a Hypoxia-Upregulated Oncogene to Regulate Cell Invasion and Resistance to NK Cell Killing in Bladder Carcinoma Cells.

OBJECTIVE: Hypoxia facilitates an aggressive phenotype and immune evasion in solid tumors including bladder cancer (BC). Sphingosine kinase 1 (SphK1) is aberrantly expressed and correlated with poor prognosis in BC patients. However, its roles in hypoxia-evoked malignancies and immune evasion in BC remain elusive. METHODS: The expression of SphK1 in BC tissues was analysed using a bioinformatics database. BC cells were transfected with si-SphK1 or recombinant HIF-1α plasmids under hypoxic conditions. The mRNA level, activity and protein expression of SphK1 were determined. Transwell assay was performed to evaluate cell invasion. After co-culture with natural killer (NK) cells, NK cell cytotoxicity to BC cells was assessed. The involvement of sphingosine-1-phosphate (S1P)/HIF-1α signaling was analysed by ELISA, qRT-PCR and western blot. RESULTS: UALCAN and GEPIA database confirmed high expression of SphK1 in BC tissues. Moreover, hypoxia increased the expression and activity of SphK1. Loss of SphK1 inhibited hypoxia-induced cell invasion. IL-2 induced NK cell activation by secreting TNF-α and IFN-γ. Hypoxia antagonized NK cell activation-evoked cytotoxicity to BC cells. Intriguingly, SphK1 knockdown reversed hypoxia-induced cell resistance to NK cell killing. Mechanically, SphK1 loss inhibited hypoxia-activated the S1P/HIF-1α signaling. However, S1P addition reversed the inhibitory effects of SphK1 down-regulation on hypoxia-activated S1P/HIF-1α signaling. Notably, reactivating HIF-1α overturned the suppressive roles of SphK1 loss in decreasing hypoxia-induced cell invasion and resistance to NK cell cytotoxicity. CONCLUSIONS: Targeting SphK1 may inhibit hypoxia-evoked invasion and immune evasion via the S1P/HIF-1α signaling, indicating a promising therapeutic target for BC.

A novel near-infrared fluorescent probe for rapid sensing of HClO in living cells and zebrafish.

Reactive oxygen species (ROS) are significant active species in living organisms, and their coordination maintains the function of organelles to resist the invasion of foreign substances. Hypochlorous acid (HClO) is not only an eventful signaling species but also a kind of ROS, which plays an irreplaceable role in the immune system. However, its abnormal levels can cause cell damage or even apoptosis, which in turn leads to the onset of a series of diseases such as inflammation, neurological diseases, and even cancer. Based on this, we designed a near-infrared fluorescent probe with a large Stokes shift for ultrafast response to HClO. Furthermore, the probe exhibits excellent sensitivity and selectivity toward HClO over other species. The probe was successfully applied to visualize endogenous and exogenous HClO in living cells and in zebrafish. This unique study is the key to providing a trustworthy tool for imaging based on the in vitro and in vivo imaging of endogenous HClO, which possesses great potential for the use in future studies of HClO-related biology and pathology.

Sphingolipid metabolism is associated with osteosarcoma metastasis and prognosis: Evidence from interaction analysis.

Background: Metabolism is widely involved in the occurrence and development of cancer. However, its role in osteosarcoma (OS) has not been elucidated. Methods: The open-accessed data included in this study were downloaded from The Cancer Genome Atlas (TCGA) database (TARGET-OS project). All the analysis was performed in R environments. Results: Based on the single sample gene set enrichment analysis algorithm, we quantified 21 metabolism terms in OS patients. Among these, sphingolipid metabolism was upregulated in the metastatic OS tissue and associated with a worse prognosis, therefore aroused our interest and selected for further analysis. Our result showed that sphingolipid metabolism could activate the Notch signaling and angiogenesis pathway, which might be responsible for the metastasis ability and poor prognosis. A protein-protein interaction network was constructed to illustrate the interaction of the differentially expressed genes between high and low sphingolipid metabolism. Immune analysis showed that multiple immune terms were upregulated in patients with high sphingolipid metabolism activity. Then, a prognosis model was established based on the identified DEGs between patients with high and low sphingolipid metabolism, which showed great prediction efficiency. Pathway enrichment showed the pathway of myogenesis, spermatogenesis, peroxisome, KRAS signaling, pancreas beta cells, apical surface, MYC target, WNT beta-catenin signaling, late estrogen response and apical junction was significantly enriched in high risk patients. Moreover, we found that the model genes MAGEB1, NPIPA2, PLA2G4B and MAGEA3 could effectively indicate sphingolipid metabolism and risk group. Conclusions: In summary, our result showed that sphingolipid metabolism is associated with osteosarcoma metastasis and prognosis, which has the potential to be a therapeutic target for OS.

Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion.

High cholesterol is a major risk factor for cardiovascular disease1. Currently, no drug lowers cholesterol through directly promoting cholesterol excretion. Human genetic studies have identified that the loss-of-function Asialoglycoprotein receptor 1 (ASGR1) variants associate with low cholesterol and a reduced risk of cardiovascular disease2. ASGR1 is exclusively expressed in liver and mediates internalization and lysosomal degradation of blood asialoglycoproteins3. The mechanism by which ASGR1 affects cholesterol metabolism is unknown. Here, we find that Asgr1 deficiency decreases lipid levels in serum and liver by stabilizing LXRα. LXRα upregulates ABCA1 and ABCG5/G8, which promotes cholesterol transport to high-density lipoprotein and excretion to bile and faeces4, respectively. ASGR1 deficiency blocks endocytosis and lysosomal degradation of glycoproteins, reduces amino-acid levels in lysosomes, and thereby inhibits mTORC1 and activates AMPK. On one hand, AMPK increases LXRα by decreasing its ubiquitin ligases BRCA1/BARD1. On the other hand, AMPK suppresses SREBP1 that controls lipogenesis. Anti-ASGR1 neutralizing antibody lowers lipid levels by increasing cholesterol excretion, and shows synergistic beneficial effects with atorvastatin or ezetimibe, two widely used hypocholesterolaemic drugs. In summary, this study demonstrates that targeting ASGR1 upregulates LXRα, ABCA1 and ABCG5/G8, inhibits SREBP1 and lipogenesis, and therefore promotes cholesterol excretion and decreases lipid levels.

Early Clinical and Radiographic Outcomes of Robot-Assisted Versus Conventional Manual Total Knee Arthroplasty: A Randomized Controlled Study.

OBJECTIVE: Robot-assisted surgery has been promoted worldwide in recent years. The development of a domestic orthopaedic robot and its clinical application are therefore of great significance. This study aimed to compare the early clinical and radiographic outcomes of domestic robot-assisted total knee arthroplasty (RA-TKA) with conventional manual total knee arthroplasty (CM-TKA). METHODS: A total of 77 patients who underwent primary single-sided TKA from June to December 2020 were prospectively enrolled; resulting in the inclusion of 72 patients. The patients were randomly divided into the RA-TKA group (37 cases, with TKA being assisted by the Yuanhua Orthopaedic Robotic System) and the CM-TKA group (35 cases, with TKA being performed using conventional tools). Knee function was evaluated by the knee range of motion (ROM), the American Knee Society Score (KSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Postoperative radiographic results were evaluated by full-length weight-bearing X-rays of the lower limb and anteroposterior and lateral X-rays of the knee were obtained preoperatively and at 90 days postoperative. The operative duration, blood loss, postoperative knee function, radiographic outcomes, and incidence of complications were compared by Student's t-test, Mann-Whitney U test, or chi-square test. Serum levels of inflammatory markers before the operation and 1, 3, and 30 days after the operation were recorded and compared between the two groups. RESULTS: The operation was significantly longer in the RA-TKA group than in the CM-TKA group (154.3 vs 115.2 min, p < 0.001). There was no significant difference in blood loss (933 vs 863 ml, p = 0.519) between the two groups. The knee ROM, KSS, and WOMAC were significantly improved in both groups 90 days after the operation compared with before the operation (p < 0.05), but there were no significant differences between the two groups (p > 0.05). The incidence of postoperative deep vein thrombosis was not statistically different between the two groups. In the radiographic findings at 90 days postoperatively we found the frequency of lateral tibial component (LTC) angle outliers was significantly lower in the RA-TKA group (3.0% vs 29.4%, p = 0.003). The neutrophil-to-lymphocyte ratio (NLR) was significantly lower in the RA-TKA group than in the CM-TKA group on day 1 after surgery (9.9 vs 12.7, p = 0.024). CONCLUSIONS: RA-TKA requires more time than CM-TKA, which may be related to the learning curve and intraoperative registration. The short-term postoperative knee functional outcomes had no differences between the two groups, and RA-TKA improved the accuracy of tibial component alignment. Further follow-up studies are required to investigate the long-term outcomes.

Retraction: The lnc-SNHG1 Gene Is Overexpressed and Correlates with Increased White Blood Cell Count, Poor Induction Treatment Response, and Poor Survival Profile in Adult Acute Myeloid Leukemia

Objective: Long noncoding RNA small nucleolar RNA host gene 1 (lnc-SNHG1) is involved in leukemogenesis via mediating multiple pathways. The current study aimed to further explore its clinical roles in disease risk, clinical features, and prognosis in patients with acute myeloid leukemia (AML). Materials and Methods: A total of 161 adult AML patients, 50 patients as a disease control (DC) group, and 50 healthy individuals as a healthy control (HC) group were enrolled and bone marrow mononuclear cells were collected. Subsequently, reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) was performed to measure lnc-SNHG1 expression. Results: Lnc-SNHG1 expression was higher in AML patients than in the DC and HC groups (both p<0.001), with good value in distinguishing AML patients from DC and HC individuals (area under the curve of 0.726 and 0.884, respectively). Moreover, lnc-SNHG1 expression was positively associated with white blood cell (WBC) count (p=0.008) but was not correlated with other clinical features such as cytogenetics, molecular genetics, and risk stratification (all p>0.05). Lnc-SNHG1 expression was also associated with a lower complete remission (CR) rate (p=0.001). Patients with lnc-SNHG1 expression in the fourth quantile had the worst CR rates compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05). Furthermore, lnc-SNHG1 expression was correlated with unsatisfactory event-free survival (p<0.001) and overall survival (p=0.002), which were worst in patients with lnc-SNHG1 expression in the fourth quantile compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05). Conclusion: Lnc-SNHG1 overexpression is associated with elevated WBC count, poor induction treatment response, and poor survival profile in cases of AML and it may serve as a potential indicator for AML.

The Effect of Calycosin-7-O-ß-D-Glucoside and its Synergistic Augmentation of Cisplatin-induced Apoptosis in SK-OV-3 Cells.

OBJECTIVE: This study aims to examine the synergetic augmentation of calycosin-7-O-ß-D-glucoside (CG) on cisplatin (CDDP) to induce apoptosis of human epithelial ovarian SK-OV-3 cancer cells. METHODS: The SK-OV-3 cells were divided into four groups: control, CDDP monotherapy, CG monotherapy, and combined CDDP and CG treatment. The cell counting kit-8 method detected cell proliferation at different times and under different treatments. Hoechst 33258 staining and annexin V-FITC/propidium iodide double staining methods were used to observe the apoptosis of the SK-OV-3 cells. The caspase-3 enzyme activity detection method, quantitative reverse transcription-polymerase chain reaction, and western blot were used to detect the apoptosis-related factors and the activities of the enzyme in SK-OV-3 cells. RESULTS: The inhibition rates of SK-OV-3 cell proliferation when exposed to 10 µM of CDDP, 50 µM of CG, and a combination of 10 µM of CDDP and 50 µM of CG were 23.2% ± 1.1%, 26.7% ± 2.0%, and 46.7% ± 1.3% after 48 h, respectively. Following the use of the drug combination, the apoptosis rate and caspase-3 enzyme activity were significantly higher than in the single-drug treatment group; the data differences were also significant (p < 0.05). At the protein and ribonucleic acid levels, CG significantly enhanced the effect of CDDP on p53, caspase-3, caspase-9, Bax, and Bcl-2. CONCLUSION: In vitro, CG significantly increases the CDDP-induced apoptosis of the SK-OV-3 cells through the p53 pathway at the cellular level. In addition, using the drugs in combination reduces the toxicity and side effects caused by using CDDP alone.

Comparison of serum inflammatory indicators and radiographic results in MAKO robotic-assisted versus conventional total knee arthroplasty for knee osteoarthritis: a retrospective study of Chinese patients.

BACKGROUND: The purpose of this study was to compare the serum inflammatory indicators and radiographic results of conventional manual total knee arthroplasty (CM-TKA) with those of MAKO-robotic assisted total knee arthroplasty (MA-TKA). METHODS: We retrospectively analysed 65 patients with knee osteoarthritis who underwent unilateral TKA from December 2020 to November 2021 in our department, which included 34 patients who underwent MA-TKA and 31 patients who underwent CM-TKA. The tourniquet time and estimated blood loss (EBL) were compared between the two groups. Knee function was evaluated using range of motion (ROM), functional score and pain score. Leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), creatine kinase (CK), and neutrophil-to-lymphocyte ratio (NLR) were recorded at 3 time points (preoperative, and on the first and third postoperative days). The hip-knee-ankle angle (HKA) and the femoral and tibial component angles in the coronal and sagittal planes were used for postoperative radiographic evaluation. RESULTS: The postoperative MA-TKA group had less EBL (496.9 ± 257.8 vs. 773.0 ± 301.3 ml, p < 0.001). There was no significant difference in knee function scores at 6 weeks postoperatively (p > 0.05). IL-6 levels were significantly lower in the MA-TKA group on the 1st postoperative day (11.4 (5.2, 21.0) vs. 24.6 (86.3, 170.8), p = 0.031). This difference in inflammatory indices became more pronounced at 72 hours after the operation because CRP, ESR, IL-6, and CK values were significantly lower in the MA-TKA group on the 3rd postoperative day (72 h) (p < 0.05). Postoperative radiographic examinations performed 2 days after the MA-TKA group suggested that only 2 cases of HKA had outlier values, which was remarkably better than the 12 cases found in the CM-TKA group (5.9% vs. 38.7%, p < 0.001). The frontal femoral component was significantly closer to the expected value of 90° in the MA-TKA group (90.9 (90.5, 92.3) vs. 92.4 (91.3, 93.7), p = 0.031). The remaining imaging evaluation parameters were not significantly different between the two groups (p > 0.05). CONCLUSIONS: In Chinese patients with OA, there was a milder systemic inflammatory response in the early postoperative period after MA-TKA compared to that of CM-TKA, as well as better radiographic outcomes. However, the tourniquet time was prolonged, and no advantages were observed in terms of functional score or pain score in the short-term follow-up.