Nomogram-based geometric and hemodynamic parameters for predicting the growth of small untreated intracranial aneurysms.

Previous studies have shown that the growth status of intracranial aneurysms (IAs) predisposes to rupture. This study aimed to construct a nomogram for predicting the growth of small IAs based on geometric and hemodynamic parameters. We retrospectively collected the baseline and follow-up angiographic images (CTA/ MRA) of 96 small untreated saccular IAs, created patient-specific vascular models and performed computational fluid dynamics (CFD) simulations. Geometric and hemodynamic parameters were calculated. A stepwise Cox proportional hazards regression analysis was employed to construct a nomogram. IAs were stratified into low-, intermediate-, and high-risk groups based on the total points from the nomogram. Receiver operating characteristic (ROC) analysis, calibration curves, decision curve analysis (DCA) and Kaplan-Meier curves were evaluated for internal validation. In total, 30 untreated saccular IAs were grown (31.3%; 95%CI 21.8%-40.7%). The PHASES, ELAPSS, and UIATS performed poorly in distinguishing growth status. Hypertension (hazard ratio [HR] 4.26, 95%CI 1.61-11.28; P = 0.004), nonsphericity index (95%CI 4.10-25.26; P = 0.003), max relative residence time (HR 1.01, 95%CI 1.00-1.01; P = 0.032) were independently related to the growth status. A nomogram was constructed with the above predictors and achieved a satisfactory prediction in the validation cohort. The log-rank test showed significant discrimination among the Kaplan-Meier curves of different risk groups in the training and validation cohorts. A nomogram consisting of geometric and hemodynamic parameters presented an accurate prediction for the growth status of small IAs and achieved risk stratification. It showed higher predictive efficacy than the assessment tools.

Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

The Efficacy of Wearable Cueing Devices on Gait and Motor Function in Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the efficacy of wearable cueing devices for improving gait and motor function of patients with Parkinson disease (PWP). DATA SOURCES: PubMed, Embase, and Cochrane CENTRAL databases were searched for papers published in English, from inception to October 23, 2022. STUDY SELECTION: Randomized controlled trials focusing on the effects of wearable cueing devices on gait and motor function in PWP were included. DATA EXTRACTION: Two reviewers independently selected articles and extracted the data. The Cochrane Bias Risk Assessment Tool was used to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of evidence. DATA SYNTHESIS: Seven randomized controlled trials with 167 PWP were included in the meta-analysis. Significant effect of wearable cueing devices on walking speed (mean difference [MD]=0.07 m/s, 95% confidence interval [CI]: [0.05, 0.09], P<.00001) was detected; however, after sensitivity analysis, no significant overall effect on walking speed was noted (MD=0.04 m/s, 95% CI: [-0.03, 0.12], P=.25). No significant improvements were found in stride length (MD=0.06 m, 95% CI: [0.00, 0.13], P=.05), the Unified Parkinson's Disease Rating Scale-III score (MD=-0.61, 95% CI: [-4.10, 2.88], P=.73), Freezing of Gait Questionnaire score (MD=-0.83, 95% CI: [-2.98, 1.33], P=.45), or double support time (MD=-0.91, 95% CI: [-3.09, 1.26], P=.41). Evidence was evaluated as low quality. CONCLUSIONS: Wearable cueing devices may result in an immediate improvement on walking speed; however, there is no evidence that their use results in a significant improvement in other gait or motor functions.

A review of 2022 Chinese clinical guidelines on the management of hepatocellular carcinoma: updates and insights.

Significant improvements in the management of hepatocellular carcinoma (HCC) during the past three years have urged the timely update of clinical guidelines in China. In brief, aMAP score is newly recommended as an effective risk stratification tool to predict HCC occurrence especially for non-cirrhotic patients. Biomarker-based surveillance including 7 micro-RNA panel and GALAD score are advocated to assist early diagnosis. China liver cancer (CNLC) staging system proposed in the 2017 guideline continues to be the standard model for staging with modifications in the treatment allocations. Conversion therapies using multi-modal, high intensity strategies are advocated to facilitate subsequent resection for patients with technically unresectable CNLC stage Ia, Ib, IIa HCC, or technically resectable IIb, IIIa HCC. Super-selective transcatheter arterial chemoembolization (TACE) with the assistance of Cone-Beam CT if necessary is recommended to guarantee the efficacy of TACE. Hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) regimen alone or in combination with systemic therapy is recommended for TACE-refractory patients or for patients with locally advanced HCC. The systemic treatments for HCC have evolved considerably since atezolizumab plus bevacizumab, and suntilimab plus bevacizumab analogue showing superior survival benefit to sorafenib, and donafenib with comparable efficacy with sorafenib are added to the first-line treatments. In addition to regorafenib, apatinib, camrelizumab and tislelizumab are added as the second-line systemic therapies for patients who progressed on sorafenib. Updates in the 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines and Japanese Society of Hepatology (JSH) consensus statement are also introduced and compared with the 2022 Chinese guidelines.

Apostasia Mitochondrial Genome Analysis and Monocot Mitochondria Phylogenomics.

Apostasia shenzhenica belongs to the subfamily Apostasioideae and is a primitive group located at the base of the Orchidaceae phylogenetic tree. However, the A. shenzhenica mitochondrial genome (mitogenome) is still unexplored, and the phylogenetic relationships between monocots mitogenomes remain unexplored. In this study, we discussed the genetic diversity of A. shenzhenica and the phylogenetic relationships within its monocotyledon mitogenome. We sequenced and assembled the complete mitogenome of A. shenzhenica, resulting in a circular mitochondrial draft of 672,872 bp, with an average read coverage of 122× and a GC content of 44.4%. A. shenzhenica mitogenome contained 36 protein-coding genes, 16 tRNAs, two rRNAs, and two copies of nad4L. Repeat sequence analysis revealed a large number of medium and small repeats, accounting for 1.28% of the mitogenome sequence. Selection pressure analysis indicated high mitogenome conservation in related species. RNA editing identified 416 sites in the protein-coding region. Furthermore, we found 44 chloroplast genomic DNA fragments that were transferred from the chloroplast to the mitogenome of A. shenzhenica, with five plastid-derived genes remaining intact in the mitogenome. Finally, the phylogenetic analysis of the mitogenomes from A. shenzhenica and 28 other monocots showed that the evolution and classification of most monocots were well determined. These findings enrich the genetic resources of orchids and provide valuable information on the taxonomic classification and molecular evolution of monocots.

Evaluation of novel anti-CEACAM6 antibody-based conjugates for radioimmunotheranostics of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor that lacks early diagnostic methods. Recently, targeted immunotherapy and radiotherapy have been integrated with radionuclide-antibody conjugate drugs, which can be used for targeted diagnosis and dynamic imaging of tumors. CEACAM6 is overexpressed in pancreatic tumors and is a potential theranostic target for PDAC. We aimed to develop a novel targeted carrier for theranostics of PDAC and other solid tumors. METHODS: Based on camelid heavy-chain-only antibodies, we developed a CEACAM6-targeting recombinant antibody NY004, and evaluated it as a novel antibody-carrier for imaging and therapy of cancer in tumor models. We labeled NY004 with theranostic nuclides and applied this self-developed antibody platform in diagnostic imaging and antitumor assessment in PDAC models. RESULTS: Through microPET, IHC, and biodistribution assays, targeting and biodistribution of [89Zr]-NY004 in solid tumors including PDAC was examined, and the investigated tumors were all CEACAM6-positive malignancies. We found that NY004 was suitable for use as a drug carrier for radioimmunotheranostics. Our study showed that NY004 was characterized by high targeted uptake and a long retention time in PANC-1 tumors (up to 6 days post-injection), with good specificity and high imaging efficiency. Therapeutic evaluation of the radionuclide-labeled antibody drug [177Lu]-NY004 in PDAC tumor-bearing model revealed that NY004 had high and prolonged uptake in tumors, relatively low non-target organ uptake, and good anti-tumor efficacy. CONCLUSION: As a drug platform for radiotheranostics, CEACAM6-specific antibody NY004 met the requirements of easy-labeling, targeting specificity, and effective persistence in pancreatic adenocarcinoma tissues. KEY POINTS: • [89Zr]-NY004 has good specificity and high imaging efficiency, and is characterized by high tumor-targeting uptake and a long tumor retention time as a PET molecular imaging tracer. • Therapeutic radionuclide-conjugated antibody drug [177Lu]-NY004 has high uptake and prolonged uptake duration in tumors, low non-target organ uptake, and significant tumor-inhibiting efficacy in PDAC model. • The self-developed antibody structure NY004 is a promising drug platform for radioimmunotheranostics of CEACAM6-positive tumors including pancreatic ductal adenocarcinoma.

Pyroptosis, Metabolism, and Oxidation in Tumorigenesis: Mechanisms and Therapeutic Implications.

Significance: Pyroptosis is a discovered programmed cell death that is mainly executed by the gasdermin protein family. Cell swelling and membrane perforation are observed when pyroptosis occurs, and is accompanied by the liberation of cell contents. Recent Advances: As the study of pyroptosis continues to progress, there is increasing evidence that pyroptosis influences the development of tumors. In addition, the relationship between pyroptosis and tumor is diverse for different tissues and cells. Critical Issues: In this review, we first introduce the research history and molecular mechanisms of pyroptosis. Then we specifically discuss the link between pyroptosis and metabolic and oxidation in tumorigenesis. In the subsequent sections, we focus on the induction of pyroptosis in cancer and its potential role as a promising target for cancer therapy, and discuss the implications of pyroptosis in tumor treatment. In addition, we further summarize the therapeutic value of pyroptosis in tumor treatment. Future Directions: A detailed understanding of the role played by pyroptosis in tumors will help us to further explore tumor formation and progression and provide ideas for the development of new pyroptosis-based therapeutic approaches for patients. Antioxid. Redox Signal. 39, 512-530.

Seasonal variations, source apportionment and dry deposition of chemical species of total suspended particulate in Pengjia Yu Island, East China Sea.

Total of 172 total suspended particulate (TSP) samples and its chemical compositions were collected and analyzed from January to December 2010 in Pengjia Yu Island, an open region in East China Sea (ECS). Despite the predominance of sea-salt major ions (Na+, Cl-), the presence of non-sea-salt SO42- (nss-SO42-) and NO3- as well as combustion-derived trace metals clearly establishes the impact of anthropogenic sources over ECS. The annual contributions of coal, heavy-fuel oil and traffic to the measured chemical species were 21.0 %, 15.0 % and 15.5 %, respectively. Especially in spring, the contributions of crustal minerals to measured chemical species during dust period (33.6 %) were higher than that (13.2 %) during non-dust period. The calculated annual average dry deposition fluxes for trace metals and total inorganic nitrogen were 246.1 ± 345.8 µg/m2/d and 2950.4 ± 2245.0 µg/m2/d, suggesting that atmospheric deposition is an important source of nutrient elements for the south of ECS.

NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-ß/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer.

Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-ß/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR-Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-ß, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-ß/Smad3 pathway.

Targeting ferroptosis in cardio-metabolic-diseases: Mechanisms and therapeutic prospects.

Cardio-metabolic-diseases (cardio-metabolic-diseases) are leading causes of death and disability worldwide and impose a tremendous burden on whole society as well as individuals. As a new type of regulated cell death (RCD), ferroptosis is distinct from several classical types of RCDs such as apoptosis and necroptosis in cell morphology, biochemistry, and genetics. The main molecular mechanisms of ferroptosis involve iron metabolism dysregulation, mitochondrial malfunction, impaired antioxidant capacity, accumulation of lipid-related peroxides and membrane disruption. Within the past few years, mounting evidence has shown that ferroptosis contributes to the pathophysiological process in cardio-metabolic-diseases. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This review comprehensively summarizes the mechanism of ferroptosis in the development and progression of cardio-metabolic-diseases, so as to provide new insights for cardio-metabolic-diseases pathophysiology. Moreover, we highlight potential druggable molecules in ferroptosis signaling pathway, and discuss recent advances in management strategies by targeting ferroptosis for prevention and treatment of cardio-metabolic-diseases.

Ferroptosis inhibitor liproxstatin-1 alleviates metabolic dysfunction-associated fatty liver disease in mice: potential involvement of PANoptosis.

Ferroptosis is a new form of regulated cell death characterized by excessive iron accumulation and uncontrollable lipid peroxidation. The role of ferroptosis in metabolic dysfunction-associated fatty liver disease (MAFLD) is not fully elucidated. In this study we compared the therapeutic effects of ferroptosis inhibitor liproxstatin-1 (LPT1) and iron chelator deferiprone (DFP) in MAFLD mouse models. This model was established in mice by feeding a high-fat diet with 30% fructose in water (HFHF) for 16 weeks. The mice then received LPT1 (10 mg·kg-1·d-1, ip) or DFP (100 mg·kg-1·d-1, ig) for another 2 weeks. We showed that both LPT1 and DFP treatment blocked the ferroptosis markers ACSL4 and ALOX15 in MAFLD mice. Furthermore, LPT1 treatment significantly reduced the liver levels of triglycerides and cholesterol, lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and ameliorated the expression of lipid synthesis/oxidation genes (Pparα, Scd1, Fasn, Hmgcr and Cpt1a), insulin resistance, mitochondrial ROS content and liver fibrosis. Importantly, LPT1 treatment potently inhibited hepatic apoptosis (Bax/Bcl-xL ratio and TUNEL+ cell number), pyroptosis (cleavages of Caspase-1 and GSDMD) and necroptosis (phosphorylation of MLKL). Moreover, LPT1 treatment markedly inhibited cleavages of PANoptosis-related caspase-8 and caspase-6 in MAFLD mouse liver. In an in vitro MAFLD model, treatment with LPT1 (100 nM) prevented cultured hepatocyte against cell death induced by pro-PANoptosis molecules (TNF-α, LPS and nigericin) upon lipid stress. On the contrary, DFP treatment only mildly attenuated hepatic inflammation but failed to alleviate lipid deposition, insulin resistance, apoptosis, pyroptosis and necroptosis in MAFLD mice. We conclude that ferroptosis inhibitor LPT1 protects against steatosis and steatohepatitis in MAFLD mice, which may involve regulation of PANoptosis, a coordinated cell death pathway that involves apoptosis, pyroptosis and necroptosis. These results suggest a potential link between ferroptosis and PANoptosis.

Ferroptotic stress facilitates smooth muscle cell dedifferentiation in arterial remodelling by disrupting mitochondrial homeostasis.

Smooth muscle cell (SMC) phenotypic switch from a quiescent 'contractile' phenotype to a dedifferentiated and proliferative state underlies the development of cardiovascular diseases (CVDs); however, our understanding of the mechanism is still incomplete. In the present study, we explored the potential role of ferroptosis, a novel nonapoptotic form of cell death, in SMC phenotypic switch and related neointimal formation. We found that ferroptotic stress was triggered in cultured dedifferentiated SMCs and arterial neointimal tissue of wire-injured mice. Moreover, pro-ferroptosis stress was activated in arterial neointimal tissue of clinical patients who underwent carotid endarterectomy. Blockade of ferroptotic stress via administration of a pharmacological inhibitor or by global genetic overexpression of glutathione peroxidase-4 (GPX4), a well-established anti-ferroptosis molecule, delayed SMC phenotype switch and arterial remodelling. Conditional SMC-specific gene delivery of GPX4 using adreno-associated virus in the carotid artery inhibited ferroptosis and prevented neointimal formation. Conversely, ferroptosis stress directly triggered dedifferentiation of SMCs. Transcriptomics analysis demonstrated that inhibition of ferroptotic stress mainly targets the mitochondrial respiratory chain and oxidative phosphorylation. Mechanistically, ferroptosis inhibition corrected the disrupted mitochondrial homeostasis in dedifferentiated SMCs, including enhanced mitochondrial ROS production, dysregulated mitochondrial dynamics, and mitochondrial hyperpolarization, and ultimately inhibited SMC phenotypic switch and growth. Copper-diacetyl-bisN4-methylthiosemicarbazone (CuATSM), an agent used for clinical molecular imaging and that potently inhibits ferroptosis, prevented SMC phenotypic switch, neointimal formation and arterial inflammation in mice. These results indicate that pro-ferroptosis stress is likely to promote SMC phenotypic switch during neointimal formation and imply that inhibition of ferroptotic stress may be a promising translational approach to treat CVDs with SMC phenotype switch.

Tuning oxygen vacancy in Bi2WO6 by heteroatom doping for enhanced photooxidation-reduction properties.

Heteroatom doping was recently regarded as an effective method to tune the band gap and improve the separation and transfer of photogenerated electron-hole pairs in semiconductor photocatalysts. Herein, a novel S,F-codoped Bi2WO6 (S,F-Bi2WO6) with suitable oxygen vacancies was synthesized via the hydrothermal-calcination and post-sulfurization, for efficient Cr(VI) reduction and methyl orange (MO) degradation under visible light. The amount of surface oxygen vacancies could be controlled by adjusting the S/F ratio during the doping process, which modulated the band structure and photogenerated charge behavior of Bi2WO6. The optimal S0.10F-Bi2WO6 exhibited an excellent photooxidation-reduction performance, which Cr(VI) reduction and MO degradation efficiencies were 1.6 and 2.6 times than those of the pristine Bi2WO6 without oxygen vacancy under visible-light, respectively. The enhanced photooxidation-reduction performance was because the right amount of oxygen vacancies could effectively narrow the bandgap and improve the separation efficiency of electron-hole pairs. Thus, this work offered a mild and simply approach for preparing heteroatom doped Bi2WO6 and a potential to be extended to the synthesis of other doped materials for environmental remediation.

Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration / 中西医结合学报

OBJECTIVE@#Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC).@*METHODS@#An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method.@*RESULTS@#We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38.@*CONCLUSION@#Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.

Advances in digital twins technology of human skeletal muscle / 生物医学工程学杂志

The human skeletal muscle drives skeletal movement through contraction. Embedding its functional information into the human morphological framework and constructing a digital twin of skeletal muscle for simulating physical and physiological functions of skeletal muscle are of great significance for the study of "virtual physiological humans". Based on relevant literature both domestically and internationally, this paper firstly summarizes the technical framework for constructing skeletal muscle digital twins, and then provides a review from five aspects including skeletal muscle digital twins modeling technology, skeletal muscle data collection technology, simulation analysis technology, simulation platform and human medical image database. On this basis, it is pointed out that further research is needed in areas such as skeletal muscle model generalization, accuracy improvement, and model coupling. The methods and means of constructing skeletal muscle digital twins summarized in the paper are expected to provide reference for researchers in this field, and the development direction pointed out can serve as the next focus of research.

Depressive symptoms are not associated with risks of rapid renal function decline or chronic kidney disease in middle-aged and elderly with normal kidney function: a longitudinal investigation / 南方医科大学学报

OBJECTIVE@#To explore the association between depressive symptoms and the risks of rapid decline in renal function and chronic kidney disease (CKD) in middle-aged and elderly with normal kidney function.@*METHODS@#The residents aged 40- 75 years with eGFR≥60 mL·min-1·1.73 m-2 without proteinuria in Lanzhou region, who participated in the "REACTION" study carried out in 2011, were selected and followed up in 2014. A total of 4961 individuals with complete and qualified data from the two surveys were included in the subsequent analysis. Based on PHQ-9 questionnaire scores, the baseline population was divided into two groups with and without depressive symptoms. Cox proportional hazard analysis was used to compare the incidences of rapid renal function decline and CKD between the two groups and study the association of depressive symptoms with the risk of these renal conditions.@*RESULTS@#PHQ-9 questionnaire scores were not found to correlate with baseline SCr, ALB, UACR or eGFR levels among the participarts (P>0.05). After a mean follow-up time of 3.4±0.6 years, 33.9% of the participants with depressive symptoms at baseline experienced a rapid decline in renal function and 3.6% progressed to CKD. During the follow-up, the incidence of rapid decline in renal function and the risk of developing CKD were not found to correlate with depressive symptoms in these participants (P>0.05) regardless of the type of the depressive syndromes.@*CONCLUSION@#Depressive symptoms are not associated with the risks of rapid renal function decline or progression to CKD in middle-aged and elderly with normal kidney function.

A convenient and time-saving method for primary culture of mature white adipocytes from mice / 南方医科大学学报

OBJECTIVE@#To establish a simple, low-cost and time-saving method for primary culture of mature white adipocytes from mice.@*METHODS@#Mature white adipocytes were isolated from the epididymis and perirenal area of mice for primary culture using a modified mature adipocyte culture method or the ceiling culture method. The morphology of the cultured mature adipocytes was observed using Oil Red O staining, and the cell viability was assessed with CCK8 method. The expression of PPARγ protein in the cells was detected with Western blotting, and the mRNA expressions of CD36, FAS, CPT1A and FABP4 were detected using RT-qPCR.@*RESULTS@#Oil Red O staining showed a good and uniform morphology of the adipocytes in primary culture using the modified culture method, while the cells cultured using the ceiling culture method exhibited obvious morphological changes. CCK8 assay showed no significant difference in cell viability between freshly isolated mature white adipocytes and the cells obtained with the modified culture method. Western blotting showed that the freshly isolated adipocytes and the cells cultured for 72 h did not differ significantly in the expression levels of PPARγ protein (P=0.759), which was significantly lowered in response to treatment with GW9662 (P < 0.001). GW9662 treatment of the cells upregulated mRNA expressions of CD36 (P < 0.001) and CPT1A (P=0.003) and down-regulated those of FAS (P=0.001) and FABP4 (P < 0.001).@*CONCLUSION@#We established a convenient and time-saving method for primary culture mature white adipocytes from mice to facilitate further functional studies of mature adipocytes.

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients / 中华医学杂志(英文版)

BACKGROUND@#This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings.@*METHODS@#We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.@*RESULTS@#Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001).@*CONCLUSION@#The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Comparison of early clinical effects between direct superior approach and posterolateral approach in hemiarthroplasty of femoral neck fracture in the elderly / 中国骨伤

OBJECTIVE@#To compare and analyze the early clinical effect of direct superior approach(DSA) and posterior lateral approach (PLA) in hemiarthroplasty for elderly patients with femoral neck fracture.@*METHODS@#The clinical data of 72 elderly patients with femoral neck fracture who underwent hemiarthroplasty from January 2020 to December 2021 were retrospectively analyzed. Among them, 36 patients were operated through minimally invasive DSA including 10 males and 26 females with an average age of (82.82±4.05) years old; the other 36 patients underwent traditional PLA including 14 males and 22 females with an average age of (82.79±3.21) years old. The perioperative related indexes and Harris scores during follow-up between two groups were compared.@*RESULTS@#Comparison of operation time between two groups, (79.41±17.39) min of DSA group was shorter than(98.45±26.58) min of PLA group;incision length (8.33±2.69) cm was shorter than (11.18±1.33) cm of PLA group;intraoperative blood loss (138.46±71.58) ml was less than (173.51±87.17) ml of PLA group, initial landing time (3.04±0.95) d was earlier than (4.52±1.10) d of PLA group, hospitalization time (8.70±1.89) d was shorter than (10.67±2.35) d of PLA group(P<0.05). There was no statistical difference in Harris score between two groups before operation(P>0.05), but Harris score in DSA group was higher than that of PLA group at 1 month after operation(P<0.05), but at 12 months after operation, the difference was not statistically significant between two groups(P>0.05).@*CONCLUSION@#Compared with PLA, DSA is superior in clinical indexes such as operation time, intraoperative blood loss, incision length, first landing time, length of hospitalization and Harris score in the first month after operation in hemi hip replacement, and has comparative advantages in promoting early postoperative rehabilitation of elderly patients with femoral neck.