ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

Purpose To investigate the clinicopathological characteristics,immunophenotype,high-risk human papillomavirus(hrHPV)infection status,treatment,and prognosis of cervical carcinoma exhibiting adenoid cystic car-cinoma(ACC)features.Methods Clinical data from 10 cases of cervical cancer with ACC features were collected.A retrospective analysis was proformed on the patients'clinicopathological data,histological features,and immunopheno-type(EnVision method),along with in situ hybridization detection of hrHPV E6/E7 mRNA covering 18 hrHPV types.Results The median age of the patients was 67.5 years,comprising 4 biopsy specimens and 6 surgical specimens.Except for 2 cases detected incidentally during physical examination,the remaining 8 cases presented with unexplained vaginal bleeding or contact bleeding.The mean tumor diameter was 4.5 cm(range:2.5 to 9.0 cm),and tumor stages were available for 8 patients(5 cases in stage Ⅰ and 1 case each in stages Ⅱ,Ⅲ,and Ⅳ).The follow-up period was 8 to 42 months,excluding 1 case lost to follow-up,2 cases(Ⅲ C1 and ⅣB)died within 1 year after surgery.Histologi-cally,4 cases exhibited pure ACC morphology,while 5 cases were mixed carcinomas(combined with squamous cell carcinoma,adenoid basal cell carcinoma,high-grade neuroendocrine carcinoma,or carcinosarcoma,respectively).The characteristic ACC morphology manifested as cribriform,pseudo-glandular,tubular,trabecular,and/or solid pat-terns with one case mixed carcinoma's lymph node metastasis showing only ACC morphology.Immunohistochemically,all 10 tumors exhibited diffuse strong positivity for p16 and p63,a high Ki67 proliferation index(40％to 90％),and wild-type p53 expression,and in 50％of cases,only a minority of cells were positive for c-MYB.Additionally,SOX10 was positive in 8 of 9 cases and CD117 was positive in 7 of 10 cases,respectively.In situ hybridization for hrHPV E6/E7 mRNA confirmed the presence of transcriptionally active HPV infection in all cases.Conclusion Cervical cancer with ACC features is rare,and predominantly occurs in postmenopausal elderly women.It represents an HPV-associat-ed high-grade carcinoma in which clinical stage is a critical prognostic factor.Immunohistochemical staining for CD117 and SOX10 aids in the pathological diagnosis of this tumor type.

OBJECTIVE To study the mechanisms and effect of sufentanil(SUF)on protection of sepsis-induced myocardial injury.METHODS The in vitro experimental models of sepsis-induced myocardial injury were estab-lished by using lipopolysaccharide(LPS).The myocardial H9C2 cells were divided into the Control group,the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group;the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group were the experimental groups.The cells from the experimental groups were respec-tively inoculated and incubated in culture media containing 25 mg/L of LPS,and the culture media were respec-tively added SUF with the terminal dose of 0,5,10,20,20 and 20 μmol/L;the culture media of the SUF-H-ComC was added ComC with the terminal dose of 10 μmol/L,and the culture media of the SUF-H-ML385 was added ML385 with the terminal dose of 5 μmol/L.The cells from the Control group were incubated in normal cul-ture media.The same amount of culture media and CCK-8 reagent without containing myocardial H9C2 cells were assigned as the blank group.The cell viability was determined by CCK-8 method,the levels of reactive oxygen species(ROS),malondialdehyde(MDA),lactate dehydrogenase(LDH),superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)were detected.The Fe2+level of the cells was detected by iron ion colorimetric meth-od.The levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in supernatant fluid of the culture media were detected with the use of enzyme-linked immunosorbent assay.The expression levels of adenosine 5'-monophosphate-activated protein kinas(AMPK),phosphorylated-AMPK(p-AMPK),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by means of Western Blot.RESULTS The cell viability of the LPS group was lower than that of the Control group;the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α of the LPS group were higher than those of the Control group;the levels of SOD and GSH-Px of the LPS group were lower than those of the Control group;the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins of the LPS group were lower than those of the Control group(P＜0.05).As compared with the LPS group,the cell viability of the SUF-L group,the SUF-M group and the SUF-H group was succes-sively increased,the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α were successively reduced,the levels of SOD and GSH-Px were successively elevated,and the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins were successively increased(P＜0.05).AMPK pathway inhibitor and Nrf2 pathway inhibitor could reverse the viability of SUF-affecting LPS-induced myocardial H9C2 cells,levels of ROS,MDA,LDH,Fe2+,SOD,GSH-Px,IL-1β,IL-6 and TNF-α and downregulated the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins(P＜0.05).CONCLUSION SUF can improve the sepsis-induced myocardial injury,and the mecha-nism may be associated with activation of AMPK/Nrf2/HO-1 signaling pathways,inhibition of ferroptosis,oxi-dative stress injury and inflammatory reactions.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence