Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

Liver fibrosis is a critical pathological process in the progression of chronic liver diseases and is mainly driven by the activation of hepatic stellate cells， and it is characterized by excessive deposition of extracellular matrix. Programmed cell death is widely observed in liver fibrosis and plays diverse roles in different types of cells. It is not only a mechanism for maintaining cellular homeostasis through metabolism， but it can also regulate the development and progression of diseases. Ferroptosis has recently emerged as a research focus due to its close association with lipid metabolism. This article systematically reviews the related concepts of lipid metabolism， ferroptosis， and liver fibrosis， analyzes the bridging role and dual regulatory function of ferroptosis in lipid metabolism and liver fibrosis， and further highlights the clinical application value of targeting ferroptosis in hepatic stellate cells for the treatment of liver fibrosis， in order to provide new perspectives for the mechanistic studies on liver fibrosis and the optimization of related clinical intervention strategies.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

ObjectiveTo evaluate the clinical effectiveness and safety of Modified Zhigancao Granules （炙甘草汤加味颗粒） for preventing the early recurrence following radiofrequency ablation in patients with atrial fibrillation （AF） of qi-yin deficiency syndrome. MethodsA multi-center， randomized， double-blind， placebo-controlled trial was designed. A total of 116 patients with atrial fibrillation of qi-yin deficiency syndrome who underwent radiofrequency ablation for the first time were enrolled from 3 centers， and they were randomly divided into a treatment group （59 cases） and a control group （57 cases）. Both groups received basic western medicine treatment after surgery. In addition， the treatment group was given oral Modified Zhigancao Granules， while the control group was given oral placebo granules. The dosage for both groups was 20 g each time， twice a day， with continuous treatment for 12 weeks. The recurrence of atrial fibrillation in both groups was recorded at 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery. The serum levels of B-type natriuretic peptide （BNP）， interleukin-6 （IL-6）， high-sensitivity C-reactive protein （hs-CRP）， and tumor necrosis factor-α （TNF-α） were detected before treatment and 12 weeks after treatment in both groups. The scores of Atrial Fibrillation Effect on QualiTy-of-life （AFEQT） Questionnaire （including scores of the daily life dimension， symptom dimension， treatment worry dimension， treatment satisfaction dimension， and total score） and traditional Chinese medicine （TCM） syndrome scores were compared before treatment and at 4 weeks， 8 weeks， and 12 weeks between groups. Safety indicators such as blood routine， urine routine， liver function， and renal function were monitored before and after treatment. ResultsNine of the treatment group and seven of the control group dropped out. Finally， 50 patients in each group were included in the statistical analysis. At 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery， the recurrence rates of AF in the treatment group were 2.0% （1/50）， 2.0% （1/50）， 4.0% （2/50）， and 10.0% （5/50）， respectively； while those in the control group were 2.0% （1/50）， 26.0% （13/50）， 28.0% （14/50）， and 34.0% （17/50）， respectively. Compared with the control group at the same time points， the early recurrence rates of AF in the treatment group were significantly lower at 4 weeks， 8 weeks， and 12 weeks after surgery （P＜0.01）. Compared with the baseline within group， BNP， hs-CRP， IL-6， and TNF-α in the treatment group all decreased after 12 weeks of treatment （P＜0.05）； the difference in hs-CRP levels （before vs. after treatment） in the treatment group was higher than that in the control group （P＜0.01）. Compared with the baseline within group， both groups showed decreases in the total score of AFEQT Questionnaire， scores of the daily life dimension， treatment worry dimension， symptom dimension， and TCM syndrome scores at 4 weeks， 8 weeks， and 12 weeks after treatment. Meanwhile， the score of the treatment satisfaction dimension of AFEQT increased in both groups （P＜0.01）， and the improvements in all the above scores in the treatment group were superior to those in the control group at all time points （P＜0.05 or P＜0.01）. All safety indicators of patients in both groups were within the normal range before treatment and at 12 weeks after treatment， and no adverse reactions or adverse events occurred in either group. ConclusionModified Zhigancao Granules can reduce the early recurrence rate following radiofrequency ablation in AF patients with qi-yin deficiency syndrome， improve clinical symptoms and quality of life， suppress inflammatory response， and show good safety.

ObjectiveTo carry out a health technology assessment （HTA） of acupuncture for secondary dysmenorrhea （SD） caused by adenomyosis and endometriosis， in order to provide a reference for relevant medical decision-making. MethodsFrom the perspective of the health system， the assessment covers seven areas， including the technical characteristics， safety， effectiveness， economics， ethical fairness， organizational adaptability， and impact on patients and society. The results are reported accordingly. ResultsThe operational specifications of acupuncture are standardized， and the conditions for its use are clearly defined. Acupuncture has a lower overall incidence of adverse events. The main adverse events are localized pain， subcutaneous bleeding， and dizziness， with most symptoms being mild， all of which have corresponding standard treatments. No reports on occupational or environmental safety were found， and the safety operation specifications are available for reference. Compared with conventional Western medicine， acupuncture demonstrates higher effectiveness. Acupuncture may improve the quality of life scores of patients， though no significant difference was observed. The cost of acupuncture is higher than that of conventional Western medicine， but its overall economic value is greater. The informed consent information is relatively comprehensive. Most patients are aware of the potential benefits and risks of acupuncture and voluntarily opt for it. The treatment process fully respects patient privacy and human rights. The clinical application of acupuncture follows the current acupuncture medical service model， with no special requirements for the level of medical institutions. Patient accessibility and affordability are suitable. Patient satisfaction is high. Most patients indicated they would choose acupuncture again for SD. The main barriers to choosing acupuncture are psychological factors （such as fear of acupuncture）， cost， and transportation issues. Nearly 70% of patients receiving acupuncture treatment benefit from medical insurance reimbursement， with reimbursement rates generally above 50%， indicating strong social security support. ConclusionThe implementation of HTA for acupuncture in the treatment of SD， using the standards for traditional Chinese medicine （TCM）， is feasible. The implementation steps are clear， the data sources for each evaluation domain are adequate， the analysis methods are practical， and the evaluation results are comprehensive. Experts recommend that the findings be used as a reference for relevant medical decision-making.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective To investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells(hUC-MSCs-Exos)administered via different routes on hypoxic ischemic brain damage(HIBD)in neonatal mice.Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups:sham operation group(n=6),model group(n=6),exosome group 1(n=8),exosome group 2(n=8).HIBD was induced using the Rice-Vannucci method.Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer(PBS)100 μl containing 10 μl exosomes within 24 h after successful modeling,respectively.Sham operation and model groups were intraperitoneal injection of PBS 100 μl.On the 7th day after the intervention,neuromotor function was assessed using the horizontal grid test and pole climbing test.On the 2nd day after the evaluation,all mice were killed and their brains were removed by decapitation.HE staining was used to observe the pathological injury of brain tissue,toluidine blue staining was used to observe the survival of neurons in cerebral cortex,and TUNEL staining was used to observe the apoptosis of cerebral cortex cells.Results Compared with sham operation group,model group,exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores(P<0.05).No significant difference was found in model group,exosome group 1 and exosome group 2 in these measures(P<0.05).Significant pathology was observed in model group,exosome group 1 and exosome group 2 compared to sham operation group(P<0.05),with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group(P<0.05).Compared with sham operation group,Nissl body count was lower in model group and exosome group 1 and exosome group 2,with a higher count in exosome group 2 compared to exosome group 1(P<0.05).Compared with sham operation group,apoptotic cells were higher in model group and exosome group 1 and exosome group 2,with a significant reduction in exosome group 1 and exosome group 2 compared to model group,and the lowest in exosome group 2(P<0.05).Conclusions hUC-MSCs-Exos can improve the neuronal motor function,promote neuron repair and inhibit apoptosis in HIBD mice.Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice,offering a convenient and rapid method suitable for clinical application.