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.

Objective:To understand the tobacco use situation and related factors among the occupational population in Beijing in 2018.Methods:The data were obtained from a special survey on “Healthy Beijing People—Ten-year Action Plan for Health Promotion (2009—2018)”. From June to September 2018, 12 908 participants were recruited from 16 districts of Beijing using the stratified sampling method combined with the typical sampling method. Questionnaires were conducted to collect basic information, work situations, tobacco exposure in public places, and smoking cessation. The Chi-square test was used to compare the differences in current smoking rates, smoking cessation rates and second-hand smoke exposure rates among participants with different characteristics. Multivariate logistic regression analysis was used to analyze the related factors of tobacco use.Results:The present smoking rate of the occupational population in Beijing was 18.0% (95% CI: 17.3%-18.7%), and the passive smoking exposure rate of non-smokers was 61.0% (95% CI: 60.1%-61.9%). The smoking cessation rate among the working population was 22.2% (95% CI: 20.7%-23.7%), and the proportion of current smokers with the intention to quit was 63.9% (1 485/2 325). The present smoking rate of employees of different genders, ages, education levels and occupational nature showed statistically significant differences ( P<0.05). The results of multivariate logistic regression analysis showed that in males, compared with the age group of 16-29 years old, the risk of smoking increased in the age groups of 30-39 years old, 40-49 years old and over 50 years old [ OR (95% CI) values were 1.49 (1.27-1.74), 1.34 (1.13-1.59) and 1.30 (1.06-1.59)]. Compared with those with junior high school or lower education, participants with high school/vocational/college education group had a higher risk of smoking ( OR=1.38, 95% CI: 1.13-1.69), while those with master′s degree or above had a lower risk of smoking ( OR=0.30, 95% CI: 0.22-0.42). The physical workers ( OR=1.28, 95% CI: 1.11-1.47) had a higher risk of smoking than the mental workers. Conclusion:The current smoking rate among the occupational population in Beijing is lower than the national level during the same period, but the exposure rate to second-hand smoke is relatively high. Age, educational level, job nature and gender are related factors of smoking.

Objective To investigate the changes in the concentration of endothelial cell-specific molecule-1(ESM-1)in cerebrospinal fluid during the acute phase of patients with moderate to severe traumatic brain injury(TBI)and its relationship with injury severity and outcomes.Methods Eighty-four patients with moderate to severe TBI who underwent ventriculostomy for intracranial pressure(ICP)monitoring at Department of Neurosurgery,Jinshan Hospital,Fudan University from Jan 2020 to Dec 2023 were selected as the study subjects,and their clinical data were collected.Based on the Glasgow Coma Scale(GCS)upon admission,TBI patients were divided into moderate TBI group(GCS 9-12,n=48)and severe TBI group(GCS 3-8,n=36).According to the Glasgow Outcome Scale(GOS)at three months post-injury,the moderate to severe TBI patients were categorized into poor outcome group(GOS 1-3)and good outcome group(GOS 4-5).Patients were also classified based on ICP monitoring values into a normal ICP group(ICP≤15 mmHg),a mildly elevated ICP group(15 mmHg

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.

Objective To explore the effect of PSMA gene on the biological behavior of prostate cancer cells and its molecular mechanism.Methods The expression of PSMA in prostate cancer and its relationship with prognosis were analyzed based on the GEPIA database.The mRNA and protein expression levels of PSMA in normal prostate epithelial cell RWPE-2 and prostate cancer cells DU145 and PC-3 were detected by RT-qPCR and Western blot,respectively.DU145 cells were used to construct knockdown cell lines,which were transfected with PSMA lentiviral knockdown plasmid and its negative control,serving as the sh PSMA group and the sh NC group,respectively;PC-3 cells were used to construct overexpression cell lines,which were transfected with PSMA lentiviral overexpression plasmid and its negative control,serving as the OE PSMA group and the OE NC group.CCK-8 assay and clone formation assay were used to detect the cell proliferation ability,wound healing assay and Transwell assay were used to detect the cell migration and invasion abilities,flow cytometry was used to detect the cell apoptosis,and Western blot was used to detect the expression of PI3K,Akt,BAX and Bcl-2 proteins.Prostate cancer cells of DU145 cell line were inoculated into the left armpit of BALB/c nude mice to form tumors,the tumor size was observed,and the tumor weight was measured;HE staining was used to evaluate the degree of damage;and the expression of PSMA was detected by immunohistochemistry.Results GEPIA database analysis showed that PSMA gene was highly expressed in prostate cancer and was related to the prognosis of prostate cancer.The results of RT-qPCR and Western blot showed that the mRNA and protein expression levels of PSMA in PC-3 and DU145 cells were higher than those in RWPE-2 cell(P<0.01).Compared with the sh NC group,the sh PSMA group showed decreased cell proliferation,migration and invasion abilities(P<0.05),and increased cell apoptosis rate(P<0.05).Compared with the OE NC group,the OE PSMA group demonstrated increased cell proliferation,migration and invasion abilities(P<0.05),and decreased apoptosis rate(P<0.05).Compared with the sh NC group,the protein expression of PI3K,Akt and Bcl-2 in the sh PSMA group decreased(P<0.05),and the protein expression of BAX increased(P<0.05).Compared with the OE NC group,the protein expression of PI3K,Akt and Bcl-2 in the OE PSMA group increased(P<0.05),and the protein expression of BAX decreased(P<0.05).Results of subcutaneous transplantation of prostate cancer in nude mice showed that the tumor weight of nude mice decreased(P<0.05),tumor cells exhibited irregular shapes,nuclei were deeply stained,and PSMA expression was weakly positive,after knocking down the PSMA.Conclusion PSMA gene may participate in regulating the proliferation,invasion,migration,and apoptosis of prostate cancer cells through the PI3K/Akt signaling pathway.

Objective:To understand the tobacco use situation and related factors among the occupational population in Beijing in 2018.Methods:The data were obtained from a special survey on “Healthy Beijing People—Ten-year Action Plan for Health Promotion (2009—2018)”. From June to September 2018, 12 908 participants were recruited from 16 districts of Beijing using the stratified sampling method combined with the typical sampling method. Questionnaires were conducted to collect basic information, work situations, tobacco exposure in public places, and smoking cessation. The Chi-square test was used to compare the differences in current smoking rates, smoking cessation rates and second-hand smoke exposure rates among participants with different characteristics. Multivariate logistic regression analysis was used to analyze the related factors of tobacco use.Results:The present smoking rate of the occupational population in Beijing was 18.0% (95% CI: 17.3%-18.7%), and the passive smoking exposure rate of non-smokers was 61.0% (95% CI: 60.1%-61.9%). The smoking cessation rate among the working population was 22.2% (95% CI: 20.7%-23.7%), and the proportion of current smokers with the intention to quit was 63.9% (1 485/2 325). The present smoking rate of employees of different genders, ages, education levels and occupational nature showed statistically significant differences ( P<0.05). The results of multivariate logistic regression analysis showed that in males, compared with the age group of 16-29 years old, the risk of smoking increased in the age groups of 30-39 years old, 40-49 years old and over 50 years old [ OR (95% CI) values were 1.49 (1.27-1.74), 1.34 (1.13-1.59) and 1.30 (1.06-1.59)]. Compared with those with junior high school or lower education, participants with high school/vocational/college education group had a higher risk of smoking ( OR=1.38, 95% CI: 1.13-1.69), while those with master′s degree or above had a lower risk of smoking ( OR=0.30, 95% CI: 0.22-0.42). The physical workers ( OR=1.28, 95% CI: 1.11-1.47) had a higher risk of smoking than the mental workers. Conclusion:The current smoking rate among the occupational population in Beijing is lower than the national level during the same period, but the exposure rate to second-hand smoke is relatively high. Age, educational level, job nature and gender are related factors of smoking.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

OBJECTIVES: This systematic review examines recent pharmacoeconomic literature on denosumab' cost-effectiveness for bone metastasis treatment, providing evidence-based insights to guide healthcare policy decisions. METHODS: A comprehensive literature search was performed across Cochrane, PubMed, EMBASE (Ovid), CNKI, and Wanfang databases to identify original articles published between 2017 and 2023. Key words consisted of bone metastases, denosumab, and cost-effectiveness in the search strategy. The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022). Data was extracted regarding methodological characteristics and cost-effectiveness analyses. RESULTS: A total of 111 studies were retrieved, of which 6 met the inclusion criteria. All included studies were based on clinical trials and published literature data and exhibited high methodological quality. Up to 83% (5 out of 6) of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid. The adjusted incremental cost-effectiveness ratios varied substantially by tumor type, ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained. CONCLUSIONS The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid. The application of CHEER (2022) enhances the reliability of pharmacoeconomic evaluations.
Denosumab/therapeutic use* ; Humans ; Bone Neoplasms/economics* ; Cost-Benefit Analysis

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*