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.

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.

In July 2024,the Diagnosis Related Groups(DRG)2.0 is released based on the Notice from the National Healthcare Security Administration on Issuing the DRG 2.0 and Deepening the Relevant Work.Compared with DRG 1.1,version 2.0 was established based on a wider range of suggestions regarding the Adjacent Diagnosis Related Groups(ADRG),Major Comorbidity or Complication(MCC),and Comorbidity or Complication(CC)from various institutions.A list of disease diagnoses and surgical operations that are not used as grouping rules was compiled,and grouping efficacy was further improved by upgrading the algorithms for MCC and CC with the help of AI.Meanwhile,it is necessary to pay more attention to the number of cases of ADRG,the better methods to list the MCC/CC,the suggestions of various doctors and continuously standardize the data and update the grouping scheme of DRG.

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.

Objective:To investigate the clinical effect of ultrasound bone knife bone window technique combined with viscous bone in mandibular cysts and its impact on postoperative bone defect repair.Methods:60 patients with mandibular cysts who visited our hospital from January 2024 to June 2024 were selected as the study subjects,they were randomly divided into control group(30 cases)and experimental group(30 cases).The control group underwent traditional scraping surgery(without the use of bone defect repair materials).The experimental group used ultrasound bone knife bone window technology combined with adhesive bone treatment.The surgical time,postoperative visual pain simulation(VAS)score,intraoperative blood loss,postoperative swelling degree,and incidence of postoperative complications between the two groups were observed and compared.Bone defect repair was evaluated by cone beam computed tomography(CBCT)at 3 and 6 months postoperatively.Results:There was no significant difference in surgical time,intraoperative blood loss,postoperative swelling degree,and incidence of postoperative complications between the two groups(P＞0.05).The VAS scores of both groups at 3 and 7 d postoperative were lower than those at 1 d postoperative(P＜0.05),and the VAS score at 7 d postoperative was lower than that 3 d postoperative(P＜0.05).The VAS scores in the experimental group were significantly lower than those in the control group at 1,3 and 7 d postoperative(P＜0.05).The HU values and bone repair area ratio in the experimental group at 3 and 6 months postoperative were significantly higher than those in the control group(P＜0.05),and the HU values and bone repair area ratio in the control group and experimental group at 6 months postoperative were significantly increased compared to those at 3 months postoperative(P＜0.05).Conclusion:The combination of ultrasound bone knife bone window technology and adhesive bone treatment for mandibular cysts can significantly reduce postoperative pain,accelerate bone defect repair,and improve bone density and repair quality.Compared with traditional scraping surgery,the use of sticky bone has significant advantages in postoperative bone regeneration and does not significantly increase the risk of complications,making it of high clinical application value.

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.

Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is in-volved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregu-lation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatic-ally reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of hu-man STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Fur-thermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regula-ting the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a po-tential inhibitory factor affecting the occurrence and progression of STAD.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.