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 explore the trend of mortality rates for female breast cancer in China and quantify the impact of demographic and non-demographic factors on the burden of breast cancer mortality.Methods:Mortality data for female breast cancer from 2013 to 2021 were extracted from the Chinese Cause of Death Monitoring Dataset, and the 2000 Chinese population census data were used to standardize the mortality rates. The Joinpoint software was employed to analyze the mortality trends by calculating the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC). The population decomposition method was utilized to quantify the impact of changes in population age structure, population size, and non-demographic factors on the burden of breast cancer mortality.Results:From 2013 to 2021, the crude mortality rate for female breast cancer in China showed an increasing trend, with an AAPC of 2.3% (95% CI: 1.7%-2.9%). The standardized mortality rate remained relatively stable, with an AAPC of -0.2% (95% CI: -1.6%-1.3%). However, Joinpoint trend analysis indicated that the standardized mortality rate had a turning point in 2017, with a rapid increase before this year (APC: 3.9%, 95% CI: 1.1%-6.9%), and a rapid decline after this year (APC: -4.1%, 95% CI: -6.8% to -1.4%). The growth speed of crude mortality rates in rural areas was higher than that in urban areas, with AAPCs of 3.0% (95% CI: 2.4%-3.5%) and 1.3% (95% CI: 0.4%-2.2%), respectively. The standardized mortality rate in rural areas remained relatively stable, with an AAPC of 0.6% (95% CI: -1.0%-2.2%), while in urban areas, it showed a decreasing trend, with an AAPC of -1.1% (95% CI: -2.2%-0.0%). In the eastern, central, and western regions, the crude mortality rates all showed an increasing trend, with AAPCs of 1.7% (95% CI: 0.7%-2.8%), 3.8% (95% CI: 2.5%-5.2%), and 2.2% (95% CI: 0.5%-4.0%), respectively, while the standardized mortality rates remained relatively stable, with AAPCs of -0.3% (95% CI: -1.7%-1.2%), 0.6% (95% CI: -1.2%-2.4%), and 0.0% (95% CI: -2.2%-2.2%), respectively. Compared with 2013, the number of deaths in 2021 increased by 42.8%, of which changes in population age structure accounted for 21.3%, the age structure changes of urban and rural residents contributed 22.8% and 19.2%, respectively, to the whole changes caused by population age structure, while those in the eastern, central, and western regions contributed 20.6%, 24.3%, and 15.9%, respectively.Demographically, the changes in population size accounted for 18.3%, and non-demographic factors only accounted for 3.2%. Conclusions:From 2013 to 2021, the crude mortality rate for female breast cancer in China continued to rise, a trend mainly influenced by population age structure, with the fastest growth rates in crude mortality rates observed in rural areas and the central region. After adjusted for age structure, the standardized mortality rate for female breast cancer in China began to decline from 2017.

Objective:To investigate the application value of multi-parameter ultrasound in the non-invasive assessment of renal fibrosis in patients with chronic kidney disease（CKD）.Methods:From December 2023 to April 2024，77 CKD patients（CKD group）and 30 healthy individuals（control group）from Renmin Hospital of Wuhan University were prospectively collected. The CKD group was further classified into mild（ n = 30），moderate（ n = 25）and severe（ n = 22）groups according to pathological assessment of renal fibrosis. Ultrasound parameters and clinical data of all patients were collected for group comparisons. Ultrasound parameters that showed statistically significant differences in univariate analysis were incorporated into a Logistic regression model to identify independent influencing factors. ROC curve was constructed，and the area under the curve（AUC）was calculated for statistical evaluation. Results:① The moderate and severe groups compared to control group，as well as the severe group compared to the mild and moderate groups，showed increased levels of SCr and BUN，and decreased level of eGFR，with statistically significant differences（all P < 0.05）. The kidney length and renal parenchymal thickness in the moderate group were smaller than those in the control group，while the kidney length，renal parenchymal thickness，and renal cortical thickness in the severe group were smaller than those in the control，mild，and moderate groups，with statistically significant differences among the groups（all P < 0.05）. The Vmax in the severe group was lower than those in the control，mild，and moderate groups，while the RI was higher than those in the control，mild，and moderate groups，with statistically significant differences（all P < 0.05）. ②In superb microvascular imaging，perfusion levels were predominantly grade 5 in the control and mild groups（83.3%，25/30；70.0%，21/30），grade 4 in the moderate group（48.0%，12/25），and grade 3 in the severe group（63.6%，14/22）. No significant differences were observed between the mild and control groups，or between the moderate and severe groups（all P>0.05），significant differences in blood flow perfusion were found between other groups（ P < 0.05）.③Shear wave elastography and super-resolution imaging revealed that mean of Young's modulus（Emean）in renal cortex increased progressively from the mild to the severe group，while microvascular density decreased. Except for Emean，which did not show significant differences between the moderate and severe groups（ P > 0.05），all other parameters showed significant differences between groups（ P < 0.05）. ④ROC curve analysis indicated that differentiating the control group from the mild group using Emean and microvascular density，the AUC was 0.769（95% CI = 0.631 - 0.872， P<0.001），with a sensitivity of 0.821 and specificity of 0.539. For the combined use of Emean，microvascular density，peak inter-arterial velocity，and resistance index for distinguishing mild from moderate-to-severe fibrosis resulted in an AUC of 0.902（95% CI = 0.843 - 0.972，P < 0.001），with a sensitivity of 0.967 and specificity of 0.755. These multi-parameter combined diagnostic approaches outperformed single ultrasound parameters. Conclusions:Multi-parameter ultrasound technology can display multidimensional renal changes in patients with CKD and effectively assess the degree of renal fibrosis. It is expected to become a non-invasive，highly sensitive tool for evaluating renal fibrosis in CKD.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Objective To investigate the risk factors of hemodynamic instability after carotid artery stenting by meta-analysis.Methods Ten databases were searched:PubMed,ProQuest,ScienceDirect,Embase,Cochrane Library,Web of Science,China Knowledge Network,Wanfang Data,VIP Information Database,and China Biomedical Database.The search date was from inception until 2 February 2024,and meta-analysis was performed using Stata 16.0 statistical software.Results A total of 27 studies with 4199 subjects and 22 influencing factors were included.The studies showed a 37.4％(95％CI 30.3％-44.8％)incidence of haemodynamic instability after carotid stenting,Meta-analysis determined that age＞60 years(P＜0.001),hypertension(P＜0.001),calcified plaque(P＜0.001),stenosis＞70％(P=0.008),eccentric plaque(P=0.002),distance from the largest stenosis to the carotid bifurcation≤ 10 mm(P＜0.001),stenosis involvement of the balloon or bifurcation(P＜0.001),balloon post-dilation(P=0.003),open-loop stenting(P＜0.001),dilated balloon diameter≥5 mm(P=0.002),repeat balloon dilation(P=0.011)and balloon dilation pressure≥8 atm(P＜0.001)are risk factors for intraoperative and postoperative haemodynamic instability in patients undergoing carotid artery stenting surgery.Statin use was a protective factor(P＜0.001).Conclusions Medical staff working in the clinic should assess the patient's condition preoperatively,identify risk factors that may lead to haemodynamic instability,and avoid unnecessary intraoperative stimulation of patients who are already in a high-risk state.Reduce postoperative clinical complications in patients with carotid artery stenosis and improve patient recovery.

Objective To investigate the risk factors of hemodynamic instability after carotid artery stenting by meta-analysis.Methods Ten databases were searched:PubMed,ProQuest,ScienceDirect,Embase,Cochrane Library,Web of Science,China Knowledge Network,Wanfang Data,VIP Information Database,and China Biomedical Database.The search date was from inception until 2 February 2024,and meta-analysis was performed using Stata 16.0 statistical software.Results A total of 27 studies with 4199 subjects and 22 influencing factors were included.The studies showed a 37.4％(95％CI 30.3％-44.8％)incidence of haemodynamic instability after carotid stenting,Meta-analysis determined that age＞60 years(P＜0.001),hypertension(P＜0.001),calcified plaque(P＜0.001),stenosis＞70％(P=0.008),eccentric plaque(P=0.002),distance from the largest stenosis to the carotid bifurcation≤ 10 mm(P＜0.001),stenosis involvement of the balloon or bifurcation(P＜0.001),balloon post-dilation(P=0.003),open-loop stenting(P＜0.001),dilated balloon diameter≥5 mm(P=0.002),repeat balloon dilation(P=0.011)and balloon dilation pressure≥8 atm(P＜0.001)are risk factors for intraoperative and postoperative haemodynamic instability in patients undergoing carotid artery stenting surgery.Statin use was a protective factor(P＜0.001).Conclusions Medical staff working in the clinic should assess the patient's condition preoperatively,identify risk factors that may lead to haemodynamic instability,and avoid unnecessary intraoperative stimulation of patients who are already in a high-risk state.Reduce postoperative clinical complications in patients with carotid artery stenosis and improve patient recovery.

Objective:To investigate the application value of multi-parameter ultrasound in the non-invasive assessment of renal fibrosis in patients with chronic kidney disease（CKD）.Methods:From December 2023 to April 2024，77 CKD patients（CKD group）and 30 healthy individuals（control group）from Renmin Hospital of Wuhan University were prospectively collected. The CKD group was further classified into mild（ n = 30），moderate（ n = 25）and severe（ n = 22）groups according to pathological assessment of renal fibrosis. Ultrasound parameters and clinical data of all patients were collected for group comparisons. Ultrasound parameters that showed statistically significant differences in univariate analysis were incorporated into a Logistic regression model to identify independent influencing factors. ROC curve was constructed，and the area under the curve（AUC）was calculated for statistical evaluation. Results:① The moderate and severe groups compared to control group，as well as the severe group compared to the mild and moderate groups，showed increased levels of SCr and BUN，and decreased level of eGFR，with statistically significant differences（all P < 0.05）. The kidney length and renal parenchymal thickness in the moderate group were smaller than those in the control group，while the kidney length，renal parenchymal thickness，and renal cortical thickness in the severe group were smaller than those in the control，mild，and moderate groups，with statistically significant differences among the groups（all P < 0.05）. The Vmax in the severe group was lower than those in the control，mild，and moderate groups，while the RI was higher than those in the control，mild，and moderate groups，with statistically significant differences（all P < 0.05）. ②In superb microvascular imaging，perfusion levels were predominantly grade 5 in the control and mild groups（83.3%，25/30；70.0%，21/30），grade 4 in the moderate group（48.0%，12/25），and grade 3 in the severe group（63.6%，14/22）. No significant differences were observed between the mild and control groups，or between the moderate and severe groups（all P>0.05），significant differences in blood flow perfusion were found between other groups（ P < 0.05）.③Shear wave elastography and super-resolution imaging revealed that mean of Young's modulus（Emean）in renal cortex increased progressively from the mild to the severe group，while microvascular density decreased. Except for Emean，which did not show significant differences between the moderate and severe groups（ P > 0.05），all other parameters showed significant differences between groups（ P < 0.05）. ④ROC curve analysis indicated that differentiating the control group from the mild group using Emean and microvascular density，the AUC was 0.769（95% CI = 0.631 - 0.872， P<0.001），with a sensitivity of 0.821 and specificity of 0.539. For the combined use of Emean，microvascular density，peak inter-arterial velocity，and resistance index for distinguishing mild from moderate-to-severe fibrosis resulted in an AUC of 0.902（95% CI = 0.843 - 0.972，P < 0.001），with a sensitivity of 0.967 and specificity of 0.755. These multi-parameter combined diagnostic approaches outperformed single ultrasound parameters. Conclusions:Multi-parameter ultrasound technology can display multidimensional renal changes in patients with CKD and effectively assess the degree of renal fibrosis. It is expected to become a non-invasive，highly sensitive tool for evaluating renal fibrosis in CKD.

Objective:To explore the trend of mortality rates for female breast cancer in China and quantify the impact of demographic and non-demographic factors on the burden of breast cancer mortality.Methods:Mortality data for female breast cancer from 2013 to 2021 were extracted from the Chinese Cause of Death Monitoring Dataset, and the 2000 Chinese population census data were used to standardize the mortality rates. The Joinpoint software was employed to analyze the mortality trends by calculating the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC). The population decomposition method was utilized to quantify the impact of changes in population age structure, population size, and non-demographic factors on the burden of breast cancer mortality.Results:From 2013 to 2021, the crude mortality rate for female breast cancer in China showed an increasing trend, with an AAPC of 2.3% (95% CI: 1.7%-2.9%). The standardized mortality rate remained relatively stable, with an AAPC of -0.2% (95% CI: -1.6%-1.3%). However, Joinpoint trend analysis indicated that the standardized mortality rate had a turning point in 2017, with a rapid increase before this year (APC: 3.9%, 95% CI: 1.1%-6.9%), and a rapid decline after this year (APC: -4.1%, 95% CI: -6.8% to -1.4%). The growth speed of crude mortality rates in rural areas was higher than that in urban areas, with AAPCs of 3.0% (95% CI: 2.4%-3.5%) and 1.3% (95% CI: 0.4%-2.2%), respectively. The standardized mortality rate in rural areas remained relatively stable, with an AAPC of 0.6% (95% CI: -1.0%-2.2%), while in urban areas, it showed a decreasing trend, with an AAPC of -1.1% (95% CI: -2.2%-0.0%). In the eastern, central, and western regions, the crude mortality rates all showed an increasing trend, with AAPCs of 1.7% (95% CI: 0.7%-2.8%), 3.8% (95% CI: 2.5%-5.2%), and 2.2% (95% CI: 0.5%-4.0%), respectively, while the standardized mortality rates remained relatively stable, with AAPCs of -0.3% (95% CI: -1.7%-1.2%), 0.6% (95% CI: -1.2%-2.4%), and 0.0% (95% CI: -2.2%-2.2%), respectively. Compared with 2013, the number of deaths in 2021 increased by 42.8%, of which changes in population age structure accounted for 21.3%, the age structure changes of urban and rural residents contributed 22.8% and 19.2%, respectively, to the whole changes caused by population age structure, while those in the eastern, central, and western regions contributed 20.6%, 24.3%, and 15.9%, respectively.Demographically, the changes in population size accounted for 18.3%, and non-demographic factors only accounted for 3.2%. Conclusions:From 2013 to 2021, the crude mortality rate for female breast cancer in China continued to rise, a trend mainly influenced by population age structure, with the fastest growth rates in crude mortality rates observed in rural areas and the central region. After adjusted for age structure, the standardized mortality rate for female breast cancer in China began to decline from 2017.