Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, damage to bone tissue microstructure, increased bone fragility, and susceptibility to fractures, while sarcopenia is a syndrome characterized by progressive reduction in overall muscle mass and functional decline. Based on the common pathophysiological mechanism and close correlation between the two, the concept of "osteosarcopenia" has gradually emerged to describe the simultaneous attenuation of muscles and bones. Signaling pathways serve as important signal transmission channels between muscles and bones, and if abnormal, they can lead to osteosarcopenia. The aim of this article, therefore, is to review the signaling pathways related to osteogenesis and myogenesis, such as Hedgehog, Hippo, mTOR, MAPK, in order to provide new ideas for targeted treatment of osteosarcopenia.

Objective:To understand the clinical characteristics of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with renal injury after antiviral therapy in Henan Province, and to explore the risk factors of renal injury.Methods:A cross-sectional study was conducted to investigate HIV infection/AIDS patients receiving antiviral therapy in Zhengzhou Sixth People′s Hospital, Anyang Fifth People′s Hospital, Hebi Third People′s Hospital, Luo Yang Zhoushan Hospital and Lankao Central Hospital in Henan Province from April 1 to September 30, 2023. The clinical information including basic data, antiviral therapy regimens and comorbidities, and laboratory test results (blood urea nitrogen, serum creatinine, blood uric acid, urine routine, urine microalbumin, urine α 1-microglobulin (α 1-MG), urine β 2-microglobulin (β 2-MG), urine retinol binding protein (RBP), urine creatinine, HIV viral load, CD4 + T lymphocyte count) were collected. Multivariate binary logistic regression was used to analyze independent risk factors for renal injury. Results:A total of 2 526 HIV infection/AIDS patients were included, with the age of (45.52±14.28) years and 2 156 (85.4%) males. The main route of transmission was sexual transmission (91.6%, 2 314/2 526). The duration of antiviral therapy was 5.00(2.92, 8.00) years. Tenofovir (TDF)+ lamivudine (3TC)+ non-nucleoside reverse transcriptase inhibitors (NNRTI) accounted for 55.3%(1 396/2 526) of the current antiviral therapy regimen. The percentage of HIV viral load <50 copies/mL was 93.0%(2 350/2 526). The CD4 + T lymphocyte count was 476(337, 645)/μL. There were 156 patients (6.2%) complicated with hepatitis B and/or hepatitis C, 205 patients (8.1%) with diabetes, 379 patients (15.0%) with hyperlipidemia, and 189 patients (7.5%) with hyperuricemia. A total of 1 040 patients (41.2%) with renal injury were found through renal function test, including 355 cases (14.1%) with estimated glomerular filtration rate (eGFR) <60 mL/(min·1.73 m 2) or urine protein positive or urine albumin creatine ratio (UACR) ≥30 mg/g, 682 patients (27.0%) with pure tubular injury presented with only positive for urinary α 1-MG, urinary β 2-MG, or urinary RBP. eGFR< 60 mL/(min·1.73 m 2) was found in 71 cases (2.8%), eGFR from 60 to 89 mL/(min·1.73 m 2) was found in 509 cases (20.2%), and eGFR≥90 mL/(min·1.73 m 2) was found in 1 946 cases (77.0%). A total of 138 patients (5.5%) were identified as having combined chronic kidney disease (CKD). Among them, 110 patients (79.7%) were in CKD stages 1 to 2, and 117 patients (84.8%) were in urinary albumin A2 grade. Multivariate analysis of 355 patients with renal injury who had eGFR<60 mL/(min·1.73 m 2) or positive urine protein in urine routine or UACR ≥30 mg/g showed that ages of 50 to 69 years old (odds ratio( OR)=2.189, 95% confidence interval ( CI) 1.333 to 3.596, P=0.002)), ≥70 years old ( OR=5.190, 95% CI 2.912 to 9.248, P<0.001), female ( OR=1.685, 95% CI 1.241 to 2.286, P=0.001), combined opportunistic infection ( OR=2.521, 95% CI 1.567 to 4.056, P<0.001), combined hepatitis B ( OR=1.962, 95% CI 1.110 to 3.467, P=0.020), combined hepatitis C ( OR=1.883, 95% CI 1.043 to 3.400, P=0.036), combined diabetes ( OR=2.703, 95% CI 1.911 to 3.821, P<0.001), using TDF for two to four years ( OR=1.674, 95% CI 1.103 to 2.459, P=0.015), using TDF for greater than or equal to five years ( OR=1.880, 95% CI 1.287 to 2.746, P=0.001), using TDF combined with lopinavir/ritonavir (LPV/r) ( OR=3.610, 95% CI 2.273 to 5.734, P<0.001) and using TDF combined with non-LPV/r ( OR=1.495, 95% CI 1.036 to 2.157, P=0.031) were the risk factors of renal injury. Conclusions:There is a high proportion of renal injury among HIV infection/AIDS patients after antiviral therapy in Henan Province, including CKD and simple renal tubular injury. Older age, female, comorbidities, and long-term use of TDF are risk factors for renal injury.

Objective: To investigate the plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer (D-D) and fibrinogen (Fib) among patients with pneumoconiosis, so as to provide insights into the prevention of thrombosis among patients with pneumoconiosis. Methods: Ninety-six male coal workers with stable-stage pneumoconiosis admitted to China Pingmei Shenma Group Occupational Disease Prevention and Control Hospital from February 2019 to February 2021 were included in the pneumoconiosis group, and 43 male healthy volunteers in the hospital during the same period were selected as the control group. The plasma D-D, Fib, IL-6 and CRP levels were detected from subjects in the two groups. The associations of plasma D-D and Fib levels with IL-6 and CRP levels were examined using Pearson correlation analysis among pneumoconiosis patients. Results: Participants in the pneumoconiosis group and the control group had a mean age of (52.91±3.89) and (52.64±4.12) years, D-D of (1.28±0.91) and (0.44±0.11) mg/L, Fib of (4.41±0.98) and (2.88±0.61) g/L, IL-6 of (0.63±0.19) and (0.42±0.06) ng/L and CRP of (3.30±1.65) and (1.35±0.12) mg/L, respectively. Higher plasma D-D, Fib, IL-6 and CRP levels were detected in the pneumoconiosis group than in the control group (all P<0.05). The plasma D-D level correlated positively with IL-6 level among pneumoconiosis patients (r=0.347, P<0.001). Conclusion High plasma IL-6, CRP, D-D and Fib levels are detected among patients with pneumoconiosis, and the plasma D-D level correlates positively with IL-6 level among patients with pneumoconiosis.

Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma. Here, we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension (COH). In COH retinas, the microglial proliferation that occurred was inhibited by the P2X7 receptor (P2X7R) blocker BBG or P2X7R knockout, but not by the P2X4R blocker 5-BDBD. Treatment of primary cultured microglia with BzATP, a P2X7R agonist, mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway. Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration, which was completely blocked by 5-BDBD. In vivo and in vitro experiments demonstrated that ATP, released from activated Müller cells through connexin43 hemichannels, acted on P2X7R to induce microglial proliferation, and acted on P2X4R/P2X7R (mainly P2X4R) to induce microglial migration. Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.
Adenosine Triphosphate/pharmacology* ; Animals ; Cell Proliferation ; Glaucoma/metabolism* ; Mice ; Microglia/metabolism* ; Receptors, Purinergic P2X4/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Retinal Ganglion Cells/metabolism*

Lipid nanoparticle (LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology. LNPs can encapsulate and deliver a wide variety of bioactive agents, including the small molecule drugs, proteins and peptides, and nucleic acids. However, as the physicochemical properties of small- and macromolecular cargos can vary drastically, every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner. Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery. In this Review, we highlight our recent progress in the design, synthesis, characterization, evaluation, and optimization of combinatorial LNPs with novel structures and properties for the delivery of small- and macromolecular therapeutics both in vitro and in vivo. These delivery systems have enormous potentials for cancer therapy, antimicrobial applications, gene silencing, genome editing, and more. We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.

BACKGROUND: Existing cell experiments, animal experiments and clinical experiments have found that Yougui Yin can play a positive role in steroid-induced femoral head necrosis, but the specific pharmacological mechanism of Yougui Yin is not described. OBJECTIVE: To explore the mechanism of Yougui Yin in the treatment of steroid-induced femoral head necrosis based on network pharmacology, and to provide a theoretical basis for the clinical application of Yougui Yin in the treatment of steroid-induced femoral head necrosis. METHODS: The Chinese Medicine Computing System Pharmacology Analysis Platform (TCMSP) was used, with oral bioavailability and drug-like properties as the limiting conditions, to retrieve the main active ingredients of six kinds of traditional Chinese medicines including Monkshood, Cinnamon, Rehmannia glutinosa, Cornus officinalis, stir-baked rhizoma dioscoreae, wolfberry in Yougui Yin and predict key target genes. Target genes related to steroid-induced femoral head necrosis were searched in OMIM and GeneCards databases, and the intersection target genes of Yougui Yin and steroid-induced femoral head necrosis were obtained through R language, followed by drawing the Wayne diagram. Using Cytoscape 3.6.1 software, we drew a “component-disease-target” Chinese medicine regulatory network, and then established a protein-protein interaction network with the help of the STRING platform. Finally, the R language and Bioconductor platform were used to perform gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on the intersection genes. RESULTS AND CONCLUSION: There were 43 main effective components in Yougui Yin, including quercetin, glycotein, diosgenin, karanjin, stigmasterol, etc. and 102 key target genes, including ESR1, AKT1, NCOA1, PTGS1, JUN, etc. Gene ontology enrichment analysis revealed 137 molecular functions, 2 119 biological processes and 41 cell components. KEGG pathway analysis yielded 153 signal pathways. To conclude, Yougui Yin may play an anti-osteoporosis and anti-inflammatory role by regulating steroid hormone receptor, phosphatase binding and other molecular functions, participating in biological processes such as active oxygen metabolism and steroid hormone response, affecting cell composition such as membrane raft and RNA polymerase II transcription factor complex, so as to treat steroid-induced femoral head necrosis with the help of endocrine resistance and other signal pathways.

Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity, is a key regulator of cytoskeletal reorganization in dendrites and spines. Here, we investigated whether and how Rac1 modulates synaptic transmission in mouse retinal ganglion cells (RGCs) using selective conditional knockout of Rac1 (Rac1-cKO). Rac1-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents, while glycine/GABA receptor-mediated miniature inhibitory postsynaptic currents were not affected. Although the total GluA1 protein level was increased in Rac1-cKO mice, its expression in the membrane component was unchanged. Rac1-cKO did not affect spine-like branch density in single dendrites, but significantly reduced the dendritic complexity, which resulted in a decrease in the total number of dendritic spine-like branches. These results suggest that Rac1 selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.

Objective To assess the significance of the right paraesophageal node(Ⅵb area) dissection in cN0 stage papillary thyroid microcarcinoma(PTMC)central lymph node dissection.Methods The clinical data of three hundred and five cN0 PTMC patients who underwent radical thyroidectomy from 2010 to 2015 was retrospectively analyzed.The metastasis rate of central compartment(Ⅵa area.Ⅵb area)and the clinical data were collected and analyzed.Results 305 cN0 stage PTMC patients underwent total thyroidectomy and bilateral central compartment dissection or right lobectomy combined with ipsilateral central compartment dissection,the mean diameter of the tumors was 6.75 mm.The incidence rate of central compartment metastasis was 35%.The incidence rate ofⅥb area metastasis was 11.1%.The status ofⅥb area metastasis was correlated with major clinicopathologic parameters such as sex,age<45,tumor diameter≥0.8 cm,bilateral multiple lesions, capsule invasion,VI a lymph node metastasis≥3 were all related risk factors of PTMC VIb area metastasis(χ2=6.913,4.241,4.517,5.185,12.400,34.745,P<0.05).Conclusion Because of the high rate of central lymph node metastasis in patients with PTMC and the poor efficiency in the evaluation for central lymph node metastasis before operation,the right paraesophageal lymph nodes(Ⅵb area)dissection is needed to be done in cN0 stage PTMC patients with tumor size≥0.8 cm,multifocal lesions,membrane invasion,Ⅵa area metastasis≥3,especially male patients.

Objective To investigate the prognostic factors for patients with hepatitis B virus-related acute-on-chronic liver failure,and to provide a basis for clinical diagnosis and treatment.Methods A total of 172 patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure who were admitted to The First Hospital of Jilin University from January 1,2006 to January 1,2016 and had complete medical records and follow-up data were enrolled,and a retrospective analysis was performed for their clinical data and laboratory markers to determine prognostic factors.The independent-samples t test was used for comparison of continuous data between groups,the chi-square test was used for comparison of categorical data between groups,and a multivariate logistic regression analysis was performed for the indices determined to be statistically significant by the univariate analysis to screen out independent risk factors for the prognosis of patients with HBV-related acute-on-chronic liver failure.Results The multivariate logistic regression analysis was performed for the indices determined to be statistically significant by the univariate analysis,and the results showed that the prognostic factors were total bilirubin (TBil),prothrombin time activity (PTA),Na +,total cholesterol (TC),Child-Turcotte-Pugh (CTP) score,age ≥50 years,the presence of liver cirrhosis,bilirubin-enzyme separation,and complications.The multivariate regression analysis was performed for the complications determined to affect prognosis by the univariate analysis,and the results showed that the complications as risk factors were hepatic encephalopathy,hepatorenal syndrome,and infection.Conclusion TBil,PTA,Na +,TC,CTP score,age ≥50 years,the presence of liver cirrhosis,bilirubin-enzyme separation,and complications are independent risk factors for the prognosis of patients with HBV-related acute -on-chronic liver failure.Liver failure patients with hepatic encephalopathy,hepatorenal syndrome,and infection tend to have poorer prognosis.Therefore,early judgment of the prognosis of patients with liver failure is of great importance in the prevention and treatment of related complications.

Background and purpose: The previous work of this study has showed that the treatment of liver cancer cells with emodin could induce endoplasmic reticulum (ER) stress and apoptosis. Given the cross-talk between ER stress and autophagy, this study aimed to investigate whether blockage of autophagy, a defense mechanism against environmental stress, could improve the killing effect of emodin on liver cancer cells. Methods: The CYTO-ID auto-phagy detection kit and Western blot were used to determine autophagy in liver cancer cells. After combined treatment with chloroquine (CQ) and emodin, cancer cell survival was analyzed by ATPlite assay and clonogenic assay. Apoptosis was detected by both flow cytometry analysis and Western blot. Results: Autophagy could be induced in liver cancer cells after treatment with emodin. Inhibition of autophagy significantly increased growth-inhibitory effect of emodin on both HepG2 and Huh7 cancer cells. The combination treatment with CQ and emodin promoted remarkable apoptosis in liver cancer cells, evidenced by the increase in the percentage of cells in sub-G1 phase and the higher expression lever of cleaved caspase-3. Conclusion: Therapeutically targeting autophagy is capable of enhancing cytotoxicity of emodin in liver cancer cell lines.