Does the limb lengthening reduce the incidence of hip dislocation in patients with neurological disorders and insufficient muscle tension who undergoing hip arthroplasty?

Background: The soft-tissue tension is closely associated with postoperative hip dislocation in patients undergoing total hip arthroplasty (THA), especially for those patients with neurological disorders and insufficient muscle tension. The aim of this study is to explore the effect of limb lengthening on the incidence of complications following THA in patients with neurological disorders and insufficient muscle tension. Methods: This retrospective analysis examines individuals with neurological disorders, such as ischemic stroke and poliomyelitis, who underwent primary total hip arthroplasty (THA) at our medical center between January 2015 and April 2021. Demographic and baseline characteristics (such as age, gender, muscle strength) were obtained from medical records. The limb length, offset and the positional parameters of both acetabular and femoral component were measured on pre- and postoperative plain radiograph. The primary outcome was the occurrence of hip dislocation. The secondary outcome included the incidence of other complications and the hip function (determined by Harris score). The correlation between the occurrence of hip dislocation and limb lengthening was analyzed. Results: A total of 258 patients were finally analyzed. The hip dislocations were identified in 35 patients (overall incidence = 13.57%). The incidence of early dislocation was lower in patients whose limb-length discrepancy (LLD) was over 20 mm (incidence = 4.1% for LLD >20 mm, 12.2% for LLD 10 mm-20 mm and 17% for LLD <10 mm). The odds ratio (OR) was 0.206 and 95% confidence interval (CI) was 0.058-0.737 (compared between LLD <10 mm and LLD >20 mm). But the no difference was identified regarding on the incidence of late dislocation among patients with different LLD. Moreover, the overall incidence of other complications was elevated in patients with LLD >20 mm (incidence = 17.58% for LLD >20 mm, 11.11% for LLD 10 mm-20 mm and 3.19% for LLD <10 mm; OR = 6.464, 95% CI = 1.768-23.640). And the Harris scores, which reflected the hip function, was gradually decreased with the increasing in LLD. In terms of the relationship between the offset and dislocation rate, it was found that increased offset discrepancy was associated with decreased dislocation incidence (incidence = 4.71% for offset discrepancy >10 mm, 12.5% for offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy <5 mm; OR = 0.238, 95% CI = 0.076-0.742). Furthermore, increased offset discrepancy also bring a reduction in late dislocation. The incidences of late dislocation were 0%, 2.5% and 10.8% for offset discrepancy >10 mm, offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy respectively. Different from that of LDD, the incidences of other complications were similar among patients with different offset discrepancy. Besides, no influence of offset discrepancy on the hip function was identified in this study. Conclusion: Unfortunately, although increasing in limb length could partially reduce early dislocation postoperatively, it could not affect the incidence of late dislocation in those patients with neurological disorders and insufficient muscle tension. Moreover, over limb lengthening was associated with other postoperative complications and worse hip function. Instead, additional offset could reduce the probability of postoperative dislocation, without increasing the incidence of other complications. Therefore, femoral stem with lower cervico-diaphyseal angle (higher offset) should be recommended to patients with neurological disorders who were in high risk of postoperative dislocation. Isolated increasing in limb length should be avoided.

Existing hip joint disease is associated with an increased incidence of hip fracture in adults: A retrospective survey of 9710 individuals from a single center.

Objective: In hip disease patients, pain and movement restrictions might cause changes in bone strength and increase the likelihood of falls, finally leading to hip fracture. The aim of this study was to identify the incidence of, characteristics of and risk factors for hip fracture in patients with existing hip disease. Methods: This was a retrospective cohort study. Patients with existing hip disease treated at both outpatient and inpatient departments of our institute were identified by searching the electronic medical record system and followed retrospectively for the occurrence of hip fracture. Demographic and clinical characteristics, such as age, sex and kind of primary hip disease, were collected from the electronic medical record system. The incidence and timing of hip fracture were estimated, and a Cox regression model was built to identify the independent risk factors for hip fracture in these patients. Results: A total of 9710 eligible patients were included. After a mean follow-up of 3.97 years, hip fractures were identified in 95 patients, for an estimated incidence of hip fracture of 978.37 per 100,000 patients. The femoral neck was involved in 49 fractures (51.58 %), and the femoral trochanter was involved in 45 fractures (47.37 %). Four independent risk factors and one protective factor for hip fracture in patients with hip diseases were identified: age (HR = 1.116, 95 % CI = 1.094-1.138), the presence of osteonecrosis of the femoral head (HR = 2.201, 95 % CI = 1.217-3.980), a lower Harris hip score (HR = 0.966, 95 % CI = 0.949-0.982), a history of previous hip surgery (HR = 2.126, 95 % CI = 1.304-3.466) and the use of walking aids (HR = 0.588, 95 % CI = 0.354-0.975). A scoring system with a total score of 20 points was built, which included all of the above risk factors. The predictive scores for a low risk (estimated incidence of hip fracture ≤30 %), a moderate risk (estimated incidence of hip fracture 31 %-69 %), and a high risk (estimated incidence of hip fracture ≥70 %) of hip fracture were ≤8.5 points, 9.0-13.0 points and ≥13.5 points, respectively. Conclusion: The incidence of hip fracture in the special population of patients with existing hip disease was determined. Elderly patients, patients with a history of hip surgery, patients with osteonecrosis and patients with poor Harris hip scores were at increased risk of hip fracture. In patients with a predictive score greater than 9 points, indicating a moderate to high risk of hip fracture, the use of a walking aid might reduce the risk of hip fracture.

Management of esophageal cancer in patients with a right aortic arch or double aortic arch: a case series of 34 cases.

BACKGROUND: Few cases describing patients with a right aortic arch (RAA) or double aortic arch (DAA) and esophageal cancer (EC) have been reported. METHODS: We analyzed RAA and DAA cases treated with esophagectomy in our center's database and reported in English-language studies until April 1, 2023. Our study assessed the malformation characteristics and surgical details of EC patients with RAA and DAA. RESULTS: We extracted data of 24 EC patients with RAAs and 10 EC patients with DAAs. In both groups, the patients were more likely to be Japanese and male, to have squamous cell carcinoma and to have tumors located in the upper thoracic esophagus or middle thoracic esophagus. Left thoracotomy was commonly applied for RAA patients. For DAA patients, the proportions of left-sided and right-sided approaches were similar. Esophagectomy under video-assisted thoracoscopic surgery (VATS) in RAA or DAA patients had been performed on a routine basis in recent years. There were two anastomotic leakages in each group. Specifically, Kommerell diverticulum rupture occurred in 1 RAA patient; gastric tube dilation occurred in 1 DAA patient; and recurrent laryngeal nerve (RLN) injury occurred in 2 RAA patients. The postoperative course was uneventful for most patients in both cohorts. CONCLUSIONS: Esophageal carcinoma is rarely seen in patients with an RAA or DAA. To adequately dissect superior mediastinal LNs, an auxiliary incision (such as sternotomy), the left door open method or a preceding cervical procedure should be used appropriately. Esophagectomy, whether via thoracotomy or thoracoscopic surgery, can be performed safely for both RAA and DAA.

A Nickel Anchored Covalent Organic Framework as Unimolecular Metallaphotocatalyst for Visible Light Driver C-P Bond Coupling Reaction.

The urgent need to develop a sustainable and environmentally friendly method for synthesizing organophosphine compounds is underscored by their extensive applications in organic synthesis, coordination chemistry, medicinal chemistry, and photoelectric materials. Metalated covalent organic frameworks (MCOFs), which seamlessly integrate the inherent photo properties of COF with the catalytic capabilities of metal ions, offer an optimal material for efficient transformation of organics sustainably. In this study, we introduce a simple COF with nickel anchorages (Bpy-COF-NiCl2 ) as a unimolecular metallaphotocatalytic system for effective C-P bond formation. This heterogeneous photocatalyst exhibits superior catalytic performance, achieving yields of up to 95 %, and demonstrates broad substrate tolerance and functional group reactivity. Notably, the metallaphotocatalytic system has demonstrated the capability to process aryl bromides to produce the desired product, a feat not previously reported. Finally, the production and reusability test at the gram scale attests to its superior practicality for designing future organic cross-coupling reactions.

Value of CT-based radiomics in evaluating the response of bone metastases to systemic drug therapy in breast cancer patients.

BACKGROUND: This study aimed to investigate the value of nonenhanced computed tomography (CT)-based radiomics in determining disease progression in breast cancer patients with bone marrow metastases and to develop a model for assessing treatment efficacy. METHODS: A total of 134 breast cancer patients with bone metastases were enrolled from three hospitals. Nonenhanced CT was performed after two cycles of drug treatment. The images were categorized into an invalid and a valid group according to disease progression status. The largest osteolytic lesions' maximum cross-sections in the CT images were selected as regions of interest (ROIs) for feature extraction. Variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) were used to reduce feature dimensionality. K-nearest neighbor algorithm (KNN), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), logistic regression (LR), and decision tree (DT) algorithms were trained to establish radiomics models. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of the models. RESULTS: The KNN classifier demonstrated the best performance compared to the random grouping method. In the validation group, the area under the ROC curve (AUC) was 0.810. In the cross-validation method, the RF classifier showed the best performance with an AUC of 0.84. CONCLUSION: Nonenhanced CT-based radiomics provides a promising method for evaluating the efficacy of systemic drug therapy in breast cancer patients with osteolytic bone metastases.

Femoral neck fracture patients with ischaemic stroke choose hemiarthroplasty or constrained liner total hip arthroplasty? A retrospective comparative study of 199 cases.

Background: The objective of this study was to assess the long-term survival rate, complications, as well as the clinical and radiological outcomes of hemiarthroplasty and total hip arthroplasty using constrained polyethylene liners in patients with ischemic stroke. Methods: This study was a retrospective cohort study that included patients with ischemic stroke who underwent hip arthroplasty from March 2010 to September 2017. In the Constrained Acetabular Liners (CAL) group, patients received an uncemented acetabular shell with a constrained polyethylene liner. The Dual Mobility (DM) group underwent hemiarthroplasty (HA). Additionally, hip function, range of motion, quality of life, the incidence of clinical complications, and prosthesis stability were investigated. Results: 96 patients with unilateral femoral neck fractures who underwent hip replacement with CAL were included in the CAL group, while 103 patients who underwent hip replacement with a dual mobility head were included in the DM group. VAS, and SF-36 data were available for both CAL and DM groups. At the 1-year postoperative follow-up, the HHS in the CAL group was significantly lower than that in the DM group (80.83 ± 3.91 vs. 83.17 ± 4.15, P < 0.05). The VAS score in the CAL group peaked at the 1-year follow-up (2.07 ± 0.91 vs. 1.49 ± 0.85, P < 0.05). However, there were no significant differences between the two groups in terms of HSS, VAS, and SF-36 at the last follow-up after surgery. Operative time and the amount of bleeding in the DM group were significantly lower than those in the CAL group (105.30 ± 29.68 vs. 94.85 ± 31.07; 355.11 ± 123.95 vs. 302.22 ± 107.68, P < 0.05). Additionally, there was no significant difference in the mean leg length discrepancy between the two groups. Conclusion: The clinical, imaging, and postoperative complications of the CAL and DM groups were analyzed. The prognosis for DM appears to be more beneficial for early patient recovery, but a higher likelihood of recurrent dislocation is observed. CAL offers excellent stability for primary THA in high-risk patients; however, attention should be given to preventing aseptic loosening.

Lipid-lowering drugs affect lung cancer risk via sphingolipid metabolism: a drug-target Mendelian randomization study.

Background: The causal relationship between lipid-lowering drug (LLD) use and lung cancer risk is controversial, and the role of sphingolipid metabolism in this effect remains unclear. Methods: Genome-wide association study data on low-density lipoprotein (LDL), apolipoprotein B (ApoB), and triglycerides (TG) were used to develop genetic instrumental variables (IVs) for LLDs. Two-step Mendelian randomization analyses were performed to examine the causal relationship between LLDs and lung cancer risk. The effects of ceramide, sphingosine-1-phosphate (S1P), and ceramidases on lung cancer risk were explored, and the proportions of the effects of LLDs on lung cancer risk mediated by sphingolipid metabolism were calculated. Results: APOB inhibition decreased the lung cancer risk in ever-smokers via ApoB (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.70-0.92, p = 0.010), LDL (OR 0.82, 95% CI 0.71-0.96, p = 0.040), and TG (OR 0.63, 95% CI 0.46-0.83, p = 0.015) reduction by 1 standard deviation (SD), decreased small-cell lung cancer (SCLC) risk via LDL reduction by 1 SD (OR 0.71, 95% CI 0.56-0.90, p = 0.016), and decreased the plasma ceramide level and increased the neutral ceramidase level. APOC3 inhibition decreased the lung adenocarcinoma (LUAD) risk (OR 0.60, 95% CI 0.43-0.84, p = 0.039) but increased SCLC risk (OR 2.18, 95% CI 1.17-4.09, p = 0.029) via ApoB reduction by 1 SD. HMGCR inhibition increased SCLC risk via ApoB reduction by 1 SD (OR 3.04, 95% CI 1.38-6.70, p = 0.014). The LPL agonist decreased SCLC risk via ApoB (OR 0.20, 95% CI 0.07-0.58, p = 0.012) and TG reduction (OR 0.58, 95% CI 0.43-0.77, p = 0.003) while increased the plasma S1P level. PCSK9 inhibition decreased the ceramide level. Neutral ceramidase mediated 8.1% and 9.5% of the reduced lung cancer risk in ever-smokers via ApoB and TG reduction by APOB inhibition, respectively, and mediated 8.7% of the reduced LUAD risk via ApoB reduction by APOC3 inhibition. Conclusion: We elucidated the intricate interplay between LLDs, sphingolipid metabolites, and lung cancer risk. Associations of APOB, APOC3, and HMGCR inhibition and LPL agonist with distinct lung cancer risks underscore the multifaceted nature of these relationships. The observed mediation effects highlight the considerable influence of neutral ceramidase on the lung cancer risk reduction achieved by APOB and APOC3 inhibition.

Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review.

Introduction: Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications. Methods: We searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification. Results: We included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, ß-blockers, and nonsteroidal anti-inflammatory agents. Conclusion: Current evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, ß-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.

Hepatocyte TIPE2 is a fasting-induced Raf-1 inactivator that drives hepatic gluconeogenesis to maintain glucose homeostasis.

BACKGROUND: The liver regulates metabolic balance during fasting-feeding cycle. Hepatic adaptation to fasting is precisely modulated on multiple levels. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a negative regulator of immunity that reduces several liver pathologies, but its physiological roles in hepatic metabolism are largely unknown. METHODS: TIPE2 expression was examined in mouse liver during fasting-feeding cycle. TIPE2-knockout mice, liver-specific TIPE2-knockout mice, liver-specific TIPE2-overexpressed mice were examined for fasting blood glucose and pyruvate tolerance test. Primary hepatocytes or liver tissues from these mice were evaluated for glucose production, lipid accumulation, gene expression and regulatory pathways. TIPE2 interaction with Raf-1 and TIPE2 transcription regulated by PPAR-α were examined using gene overexpression or knockdown, co-immunoprecipitation, western blot, luciferase reporter assay and DNA-protein binding assay. RESULTS: TIPE2 expression was upregulated in fasted mouse liver and starved hepatocytes, which was positively correlated with gluconeogenic genes. Liver-specific TIPE2 deficiency impaired blood glucose homeostasis and gluconeogenic capacity in mice upon fasting, while liver-specific TIPE2 overexpression elevated fasting blood glucose and hepatic gluconeogenesis in mice. In primary hepatocytes upon starvation, TIPE2 interacted with Raf-1 to accelerate its ubiquitination and degradation, resulting in ERK deactivation and FOXO1 maintenance to sustain gluconeogenesis. During prolonged fasting, hepatic TIPE2 deficiency caused aberrant activation of ERK-mTORC1 axis that increased hepatic lipid accumulation via lipogenesis. In hepatocytes upon starvation, PPAR-α bound with TIPE2 promoter and triggered its transcriptional expression. CONCLUSIONS: Hepatocyte TIPE2 is a PPAR-α-induced Raf-1 inactivator that sustains hepatic gluconeogenesis and prevents excessive hepatic lipid accumulation, playing beneficial roles in hepatocyte adaptation to fasting.

Establishment of Digital PCR Method and Reference Material for Adenoviruses 40 and 41.

Coinfection with human adenovirus (HAdV) and SARS-CoV-2 has been associated with acute hepatitis in children with unknown etiology. Similar cases have been reported in many countries, and HAdV 40 and HAdV 41 have been identified. The quantification method is established based on digital PCR (dPCR) for HAdV 40/41, which is more convenient for low-concentration virus detection. The limit of detections of HAdV 40/41 dPCR were 4 and 5 copies/µL. Pseudovirus reference material (RM) that contains the highly conserved HEXON gene was developed and quantified with the dPCR method. The assigned values with expanded uncertainty were (1.43 ± 0.35) × 103 copies/µL for HAdV 40 RM and (1.21 ± 0.28) × 103 copies/µL for HAdV 41 RM. The values could be reproduced on multiple platforms. The dPCR method and pseudovirus RMs contribute to the improved accuracy of HAdV 40/41 detection, which is crucial for clinical diagnosis.

Effectiveness of Needle Aspiration versus Surgical Excision for Symptomatic Synovial Cysts of the Hip: A Single-Center, Retrospective Study.

BACKGROUND This study was performed to evaluate the clinical effectiveness of needle aspiration vs surgical excision for symptomatic synovial cysts of the hip. MATERIAL AND METHODS This retrospective study analyzed the clinical data of patients diagnosed with synovial cysts of the hip and treated in a single-center hospital from January 2012 to April 2022. Patients receiving needle aspiration were assigned to group A and those treated with surgery were assigned to group B. Demographic characteristics, etiology, symptoms, cyst location, postoperative complications and recurrence, Harris Hip Score (HHS) and Visual Analog Scale of Pain (VAS) scores before treatment and at 3, 6, and 12 months after treatment were recorded to assess hip function in both groups. RESULTS This study recruited 44 patients, with 18 patients in group A and 26 in group B, and the 2 arms were well-balanced in terms of baseline patient profiles. Needle aspiration resulted in significantly better pain mitigation for patients at 24 h, 48 h, and 72 h after treatment vs surgical interventions (P<0.05). Needle joint aspiration resulted in significantly better function restoration of the hip joint than surgery at 3 months after treatment, as evidenced by the lower HHS score of 85.31±13.16 in group A vs 78.51±11.66 in group B (P=0.002). Surgery was associated with a significantly lower incidence of disease relapse (0.00%) vs needle aspiration (27.7%) (P=0.004). CONCLUSIONS Needle aspiration in the treatment of symptomatic synovial cysts of the hip causes less damage to the soft tissue and leads to faster recovery in the short term than surgical resection. Surgical resection has a lower recurrence rate and better long-term efficacy.

Xiaoliu Pingyi Pecipe Inhibits Lung Pre-Metastatic Niche Formation and Prevents Myeloid-Derived Suppressor Cells Recruitment.

BACKGROUND: Metastasis, a leading cause of cancer-related deaths, involves complex mechanisms. The premetastatic niche (PMN) is a crucial contributor to this process. Myeloid-derived suppressor cells (MDSCs) play an important role in PMN formation and promote tumor progression and metastasis. The Xiaoliu Pingyi recipe (XLPYR), a traditional Chinese medicine, is effective in preventing postoperative recurrence and metastasis in cancer patients. OBJECTIVE: This study investigated the effects of XLPYR on MDSCs recruitment and on the expression of PMN markers and elucidated the mechanisms involved in the prevention of tumor metastasis. METHODS: C57BL/6 mice were subcutaneously injected with Lewis cells and treated with cisplatin and XLPYR. Tumors were resected after 14 days after the establishment of a model of lung metastasis, and tumor volume and weight were measured. Lung metastases were observed 21 days after resection. MDSCs in the lung, spleen, and peripheral blood were detected by flow cytometry. Western blotting, qRT-PCR and ELISA were used to detect the expression of S100A8, S100A9, MMP9, LOX, and IL-6/STAT3 in premetastatic lung tissue. RESULTS: XLPYR treatment inhibited tumor growth and prevented lung metastasis. Compared to mice without subcutaneous tumor cell transplantation, the model group had an increased proportion of MDSCs, higher expression of S100A8, S100A9, MMP9, and LOX in the premetastatic lung. XLPYR treatment reduced the proportion of MDSCs, S100A8, S100A9, MMP9, and LOX expression, and downregulated the IL-6/STAT3 pathway. CONCLUSIONS: XLPYR may prevent MDSCs recruitment and reduce the expression of S100A8, MMP9, LOX, and IL6/STAT3 in premetastatic lung tissue, thus reducing lung metastases.

Ethyl caffeate attefnuates Aß-induced toxicity in Caenorhabditis elegans AD models via the insulin/insulin-like growth factor-1 signaling pathway.

The pathogenesis of Alzheimer's disease (AD), a multifactorial progressive neurodegenerative disease associated with aging, is unclear. Ethyl caffeate is a plant polyphenol that has been reported to have neuroprotective effects, but the mechanisms by which it acts are unclear. In this study, for the first time, we investigated the molecular mechanism of its anti-AD properties using the Caernorhabditis elegans model. The results of our experiments showed that ethyl caffeate delayed the paralysis symptoms of CL4176 to a different extent and reduced the exogenous 5-hydroxytryptophan-induced paralysis phenotype. Further studies revealed that ethyl caffeate lowered Aß plaques and depressed the expression of Aß monomers and oligomers, but did not influence the mRNA levels of Aß. Moreover, it was able to bring paraquat-induced ROS levels down to near-standard conditions. Real-time quantitative PCR experiment showed a significant upregulation of the transcript abundance of daf-16, skn-1 and hsf-1, key factors associated with the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway (IIS), and their downstream genes sod-3, gst-4 and hsp-16.2. It was further shown that ethyl caffeate activated the translocation of DAF-16 and SKN-1 from the cytoplasm to the nucleus and enhanced the expression of sod-3::GFP, gst-4::GFP and hsp-16.2::GFP in transgenic nematodes. This meant that the protection against Aß toxicity by ethyl caffeate may be partly through the IIS signaling pathway. In addition, ethyl caffeate suppressed the aggregation of polyglutamine proteins in AM141, which indicated a potential protective effect against neurodegenerative diseases based on abnormal folding and aggregation of amyloid proteins. Taken together, ethyl caffeate is expected to develop as a potential drug for the management of AD.

Metastatic differentiated thyroid cancer with negative serum stimulated Tg but positive post-therapeutic 131I-SPECT/CT scintigraphy: a single-center retrospective study.

PURPOSE: This study aimed to describe the characteristics of patients with metastatic differentiated thyroid carcinoma (DTC) who had positive 131I-scintigraphy but negative stimulated thyroglobulin (sTg), and to evaluate their short-term response to radioiodine therapy (RAI). METHODS: A total of 2250 consecutive postoperative DTC patients, who underwent RAI treatment from July 2019 to June 2022, were analyzed retrospectively. The target group was defined as stimulated Tg < 2 ng/mL with TgAb < 100 IU/mL but with post-therapeutic 131I-SPECT/CT metastases. The characteristics of these patients were analyzed and the metastatic profiles were compared with TgAb positive or sTg positive ones. A cross-sectional efficacy was evaluated 6-12 months after the RAI therapy and the treatment course until the end of the study was recorded. RESULTS: 105 (4.67%) DTC patients were post-therapeutic 131I-SPECT/CT positive and sTg negative (target group). Metastatic profiles were found significant differences between sTg negative and sTg positive ones (P < 0.001). Excellent response (ER) was achieved in 72.4% of the target group between 6-12 months of cross-sectional efficacy assessment, compared with only 12.8% in sTg positive ones (P < 0.001). The majority of the target group didn't require aggressive treatment in short-term follow-up compared with sTg positive group (P < 0.001). CONCLUSION: The percentage of DTCs with negative sTg but positive post-therapeutic 131I-SPECT/CT was relatively low, but still significant. Moreover, the majority of these patients showed an ER to RAI and may not require the next course of therapy. Long-term follow-up is still necessary to assess recurrence and adapt surveillance in these patients.

The systemic immune-inflammation index was non-linear associated with all-cause mortality in individuals with nonalcoholic fatty liver disease.

OBJECTIVE: Systemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD. METHODS: Data was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan-Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines. RESULTS: A total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log2-SII group (quartile 1) and the highest log2-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47-2.37; p < 0.0001). After controlling for confounders, an increase in log2-SII was associated with an increased all-cause mortality risk of 41% for every unit raised (aHR = 1.41; 95% CI: 1.26-1.57; p < 0.0001). After adjusting for multiple potential confounders, the association between log2-SII and all-cause mortality was nonlinear, and the threshold value was 8.8. There was no association between an increase of one unit in log2-SII and all-cause mortality below the threshold (aHR = 0.90, 95% CI: 0.71-1.15, p = 0.419). However, a higher log2-SII was associated with a higher risk of death from any cause when it exceeded the threshold (aHR = 1. 73, 95% CI: 1.49-2.02, p < 0.001).Based on a study of US NAFLD patients, it was found that the baseline log2-SII is associated with all-cause mortality. Elevated SII is associated with poor survival among NAFLD patients.KEY MESSAGESUsing a large nationally representative survey of individuals among US adults, the study demonstrated that log2-SII was J-shaped and associated with all-cause death among individuals with NAFLD.Spline analyses demonstrated that the association between log2-SII and all-cause mortality was non-linear after adjusting for multiple potential confounders, and the threshold value was 8.8.Higher log2-SII associated with poor survival in NAFLD.

CRISPR-Cas12a Biosensor Array for Ultrasensitive Detection of Unamplified DNA with Single-Nucleotide Polymorphic Discrimination.

Quantitative polymerase chain reaction as a powerful tool for DNA detection has been pivotal to a vast range of applications, including disease screening, food safety assessment, environmental monitoring, and many others. However, the essential target amplification step in combination with fluorescence readout poses a significant challenge to rapid and streamlined analysis. The discovery and engineering of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) technology have recently paved the way for a novel approach to nucleic acid detection, but the majority of current CRISPR-mediated DNA detection platforms are limited by insufficient sensitivity and still require target preamplification. Herein, we report a CRISPR-Cas12a-mediated graphene field-effect transistor (gFET) array, named CRISPR Cas12a-gFET, for amplification-free, ultrasensitive, and reliable detection of both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) targets. CRISPR Cas12a-gFET leverages the multiturnover trans-cleavage activity of CRISPR Cas12a for intrinsic signal amplification and ultrasensitivity of gFET. As demonstrated, CRISPR Cas12a-gFET achieves a limit of detection of 1 aM for the ssDNA human papillomavirus 16 synthetic target and 10 aM for the dsDNA Escherichia coli plasmid target without target preamplification. In addition, an array of 48 sensors on a single 1.5 cm × 1.5 cm chip is employed to improve data reliability. Finally, Cas12a-gFET demonstrates the capability to discriminate single-nucleotide polymorphisms. Together, the CRISPR Cas12a-gFET biosensor array provides a detection tool for amplification-free, ultrasensitive, reliable, and highly specific DNA detections.

CX3CR1hi macrophages sustain metabolic adaptation by relieving adipose-derived stem cell senescence in visceral adipose tissue.

Adipose-derived stem cells (ASCs) drive healthy visceral adipose tissue (VAT) expansion via adipocyte hyperplasia. Obesity induces ASC senescence that causes VAT dysfunction and metabolic disorders. It is challenging to restrain this process by biological intervention, as mechanisms of controlling VAT ASC senescence remain unclear. We demonstrate that a population of CX3CR1hi macrophages is maintained in mouse VAT during short-term energy surplus, which sustains ASCs by restraining their senescence, driving adaptive VAT expansion and metabolic health. Long-term overnutrition induces diminishment of CX3CR1hi macrophages in mouse VAT accompanied by ASC senescence and exhaustion, while transferring CX3CR1hi macrophages restores ASC reservoir and triggers VAT beiging to alleviate the metabolic maladaptation. Mechanistically, visceral ASCs attract macrophages via MCP-1 and shape their CX3CR1hi phenotype via exosomes; these macrophages relieve ASC senescence by promoting the arginase1-eIF5A hypusination axis. These findings identify VAT CX3CR1hi macrophages as ASC supporters and unravel their therapeutic potential for metabolic maladaptation to obesity.

Clinicopathological Characteristics and Outcomes of Immunoglobulin A Nephropathy with Different Types of Dyslipidemia: A Retrospective Single-Center Study.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is one of the most common glomerulonephritic diseases in the world. Several lines of evidence have suggested that dyslipidemia is related to the disease progression and prognosis of IgAN. However, the study is scarce on the clinicopathological characteristics and outcomes of IgAN with dyslipidemia. METHODS: This study retrospectively analyzed 234 patients with biopsy-proven idiopathic IgAN at the Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and June 2021. The participants were divided into dyslipidemia (n = 119) and non-dyslipidemia (n = 115), and the dyslipidemia group was also divided into the following 4 groups: hypertriglyceridemia group, hypercholesterolemia group, mixed hyperlipidemia group, and low high-density lipoprotein cholesterol group. The estimated glomerular filtration rate (eGFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: The prevalence of dyslipidemia in IgAN patients in our center was 50.9% (119/234). The patients with dyslipidemia presented with higher systolic blood pressure (BP), diastolic BP, serum creatinine, uric acid, hemoglobin, proteinuria, and eGFR (p < 0.05). Proportions of males, hypertension, and chronic kidney disease stage 2∼5 were also higher in the dyslipidemia group (p < 0.05). Similarly, the pathological characteristics performed were worse in the dyslipidemia group. Most dyslipidemia patients had a higher percentage of mesangial hypercellularity (M1) and tubular atrophy/interstitial fibrosis (T1∼2) in the Oxford Classification's scoring system (p < 0.05). Multivariate logistic regression analysis revealed that male gender (odds ratio [OR] = 2.397, 95% confidence interval [CI]: 1.051-5.469, p = 0.038) and proteinuria (OR = 1.000, 95% CI: 1.000-1.001, p = 0.035) were possible risk factors for dyslipidemia. A total of 13 patients (13.8%) in the dyslipidemia group had an endpoint event, of which 6 patients (6.4%) had a ≥50% decrease in eGFR from baseline and 7 patients (7.4%) reached the end-stage renal disease stage. Kaplan-Meier survival curve analysis showed that patients in the dyslipidemia group had a worse outcome than those in the non-dyslipidemia group (log-rank test, p = 0.048). CONCLUSIONS: IgAN patients with dyslipidemia presented more severe clinicopathological characteristics. Male gender and proteinuria are significantly associated with the occurrence of dyslipidemia in IgAN patients. Patients in the dyslipidemia group had a worse prognosis than those in the non-dyslipidemia group, which may be essential for the disease management of IgAN and help identify the high-risk patients.

The indications for core decompression surgery in patients with ARCO stage I-II osteonecrosis of the femoral head: a new, comprehensive prediction system.

BACKGROUND: Core decompression (CD) is considered the most popular treatment method for patients with Association Research Circulation Osseous (ARCO) stage I-II osteonecrosis of the femoral head (ONFH). However, the definitive indication for CD is currently not well established. METHODS: This was a retrospective cohort study. Patients who were diagnosed with ARCO stage I-II ONFH and who underwent CD were included. According to the prognosis, the patients were divided into two groups: collapse of the femoral head after CD and noncollapse of the femoral head. Independent risk factors for the failure of CD treatment were identified. Subsequently, a new scoring system that included all these risk factors was built to help estimate the individual risk of CD failure in patients who were planning to undergo CD. RESULTS: The study included 1537 hips after decompression surgery. The overall failure rate of CD surgery was 52.44%. Seven independent prognostic factors for failed CD surgery were identified, such as male sex (HR = 75.449; 95% confidence interval (CI), 42.863-132.807), Aetiology (Idiopathic HR = 2.762; 95% CI, 2.016-3.788, Steroid-induced HR = 2.543; 95% CI, 1.852-3.685), if the patient had a seated occupation (HR = 3.937; 95% CI, 2.712-5.716), age (HR = 1.045; 95% CI, 1.032-1.058), haemoglobin level (HR = 0.909; 95% CI, 0.897-0.922), disease duration (HR = 1.217; 95% CI, 1.169-1.267) and the combined necrosis angle (HR = 1.025; 95% CI, 1.022-1.028). The final scoring system included these seven risk factors, and the area under the curve of this scoring system was 0.935 (95% confidential interval = 0.922-0.948). CONCLUSION: This new scoring system might provide evidence-based medical proof for determining whether a patient with ARCO stage I - II ONFH might benefit from CD surgery. This scoring system is crucial for making clinical decisions. Consequently, this scoring system is recommended before CD surgery, which could help determine the potential prognosis of patients.