Objective To analyze the situation of rapid antiretroviral therapy (ART) and death of HIV/AIDS in Wuhan from 1994 to 2023, and to provide a scientific basis for further rapid initiation of ART and reduction of mortality rate. Methods According to the case follow-up and treatment database of China AIDS Prevention and Control Information System, data were obtained from all the cases reported from January 1, 1994 to December 31, 2023 with the current address in Wuhan City and the review status of the final review card. The data were analyzed using Kaplan-Meier and Cox proportional hazards models. Results The total mortality rate of HIV/AIDS in Wuhan from 1994 to 2023 was 12.76%. The proportion of receiving antiretroviral therapy within 30 days increased year by year, and the mortality rate decreased year by year. After adjusting for sex, age, occupation, ethnicity, education level, mobile population, history of STD, route of infection, source of sample, and first CD4 value, receiving antiretroviral therapy within 30 days (HR=0.08, 95%CI: 0.07-0.10) was a protective factor for HIV/AIDS mortality. Conclusion Rapid antiretroviral therapy can significantly reduce the risk of HIV/AIDS death. A sustainable model of rapid initiation of antiretroviral therapy should be further established to increase the proportion of rapid antiretroviral therapy for HIV/AIDS in Wuhan.

ObjectiveTo investigate the effect and mechanism of long intergenic non-coding RNA02086 （LINC02086） overexpression mediated macrophage polarization on the proliferation， migration and invasion of gastric cancer cells. MethodsThe expression levels of LINC02086 in the human gastric epithelial cell line GES-1 and human gastric cancer cell lines HCG-27， NCI-N87， and AGS were determined by qRT-PCR. Human acute monocytic leukemia cells （THP-1） were induced to differentiate into M0 macrophages using phorbol 12-myristate 13-acetate （PMA）. HGC-27 cells were infected with either LINC02086 overexpression lentivirus （OE-LINC02086） or its negative control lentivirus （Vector）， and the culture supernatants were collected as conditioned medium （CM1）. M0 macrophages were co-cultured with the infected HGC-27 cells， and the resulting supernatants were designated as conditioned medium 2 （CM2）. M0 macrophages were treated with CM1 alone or in combination with Wnt/β-catenin pathway inhibitor IWR-1， forming the Vector+CM1， OE-LINC02086+CM1， and OE-LINC02086+CM1+IWR-1 groups， respectively. Flow cytometry was used to detect mannose receptor C-type 1 （CD206） expression， and qRT-PCR was employed to measure mRNA levels of interleukin-10 （IL⁃10）， transforming growth factor-β （TGF⁃β）， vascular endothelial growth factor （VEGF）， and chemokine ligand 22 （CCL22）. Western blot was performed to evaluate protein expression of CD206， VEGF， and key components of the Wnt/β-catenin pathway—Wnt family member 3a （Wnt3a）， glycogen synthase kinase-3β （GSK-3β）， and β-catenin. HGC-27 cells were treated with CM2 alone or combined with IWR-1， establishing the Vector+CM2， OE-LINC02086+CM2， and OE-LINC02086+CM2+IWR-1 groups. CCK-8 assay was used to evaluate cell proliferation， and Transwell assays were conducted to assess migration and invasion capabilities. ResultsCompared with GES-1 cells， the expression levels of LINC02086 were upregulated in HCG-27， NCI-N87， and AGS cells （P < 0.05）， with the smallest increase observed in HCG-27 cells. Compared with Vector+CM1 group， the level of CD206 and the expression levels of IL⁃10， TGF⁃β， VEGF and CCL22 mRNA in macrophages stimulated by OE-LINC02086+CM1 increased （P<0.05）. Meanwhile， the expression levels of Wnt3a and β-catenin proteins in cells increased （P<0.05）， and the expression level of GSK-3β protein decreased （P<0.05）. However， co-treatment with IWR-1 markedly reversed the promoting effects of LINC02086 overexpression on the expression of M2 polarization markers， including CD206， IL⁃10， and TGF⁃β mRNA， in macrophages （P<0.05）， as well as its activation of the Wnt/β-catenin signaling pathway （P<0.05）. Compared with Vector+CM2 group， HGC-27 cells infected with OE-LINC02086+CM2 had increased proliferation activity and increased number of migration and invasion cells （P<0.05）. However， the combined intervention of IWR-1 significantly reversed the promotion of LINC02086 overexpression on the proliferation， migration and invasion of HGC-27 cells （P<0.05）. ConclusionLINC02086 overexpression promotes the proliferation， migration and invasion of gastric cancer cells by activating Wnt/β-catenin pathway to mediate M2 polarization of macrophages.

ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*