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 investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation （补肾活血方， BSHXF） in Parkinson's disease （PD） from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups， control group， model group， Madopar group， and BSHXF group， with 12 rats in each group. Except for the control group， rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling， rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/（kg·d）， while rats in the Madopar group received Madopar tablet suspension at 2 g/（kg·d）. Rats in the control group and the model group were administered distilled water by gavage at 10 ml/（kg·d）. All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test （total distance traveled， average speed， and total distance traveled in the central zone）， rotarod test （latency to fall）， and balance beam test （traversal time）. Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein （α-syn）， phosphorylated serine 129 α-synuclein （pSer129-α-syn）， vesicle-associated membrane protein 2 （VAMP2）， and synaptophysin （SYP） in the substantia nigra and colon tissues. The mRNA expression levels of α-syn， VAMP2， and SYP were detected by RT-PCR， and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 （ZO-1） and occludin in colon tissues， as well as tyrosine hydroxylase （TH） levels in substantia nigra tissues. ResultsCompared with the control group， rats in the model group showed reduced total distance traveled， average speed， and central-zone distance in the open field test， decreased latency to fall in the rotarod test， and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn， as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues， whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased， while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased （P＜0.05）. HE staining showed focal necrosis in the mucosal layer of colon tissues， disappearance of some intestinal glands， extensive inflammatory cell infiltration， and proliferation of fibrous connective tissue in the submucosa. Compared with the model group， both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators （P＜0.05）. Pathological damage in colon tissues was also alleviated， with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group， rats in the BSHXF group exhibited increased average speed， central-zone distance， and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased， while VAMP2 protein expression was increased. In colon tissues， SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased （P＜0.05）. ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling， restoring intestinal barrier integrity， and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.

ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation （补肾活血方， BSHXF） in Parkinson's disease （PD） from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups， control group， model group， Madopar group， and BSHXF group， with 12 rats in each group. Except for the control group， rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling， rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/（kg·d）， while rats in the Madopar group received Madopar tablet suspension at 2 g/（kg·d）. Rats in the control group and the model group were administered distilled water by gavage at 10 ml/（kg·d）. All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test （total distance traveled， average speed， and total distance traveled in the central zone）， rotarod test （latency to fall）， and balance beam test （traversal time）. Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein （α-syn）， phosphorylated serine 129 α-synuclein （pSer129-α-syn）， vesicle-associated membrane protein 2 （VAMP2）， and synaptophysin （SYP） in the substantia nigra and colon tissues. The mRNA expression levels of α-syn， VAMP2， and SYP were detected by RT-PCR， and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 （ZO-1） and occludin in colon tissues， as well as tyrosine hydroxylase （TH） levels in substantia nigra tissues. ResultsCompared with the control group， rats in the model group showed reduced total distance traveled， average speed， and central-zone distance in the open field test， decreased latency to fall in the rotarod test， and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn， as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues， whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased， while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased （P＜0.05）. HE staining showed focal necrosis in the mucosal layer of colon tissues， disappearance of some intestinal glands， extensive inflammatory cell infiltration， and proliferation of fibrous connective tissue in the submucosa. Compared with the model group， both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators （P＜0.05）. Pathological damage in colon tissues was also alleviated， with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group， rats in the BSHXF group exhibited increased average speed， central-zone distance， and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased， while VAMP2 protein expression was increased. In colon tissues， SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased （P＜0.05）. ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling， restoring intestinal barrier integrity， and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， with a complex pathogenesis. Mitochondria play a pivotal role in this disease process， and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance， while mitochondrial DNA （mtDNA） is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA， it can be recognized by intracellular pattern recognition receptors， which in turn triggers innate immune responses and causes tissue damage， forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently， there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway， its pathological role in the development and progression of MAFLD， and the current intervention strategies targeting this mechanism， in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.

Objective: To construct a scientific and perfect evaluation index system of infectious disease prevention and control ability in colleges and universities, so as to provide reference tools for colleges and universities to effectively respond to infectious disease. Methods: The initial framework of the evaluation index system of infectious disease prevention and control ability in colleges and universities was constructed by using literature analysis method. Experts familiar with infectious disease prevention and control or school health work were selected to conduct two rounds( n =16，18) of Delphi expert consultation for determining the evaluation index system. Analytical hierarchy process was used to calculate the index weights and combined weights. About 198 prevention and control personnel were conveniently selected from 3 universities in Inner Mongolia Autonomous Region to comprehensively evaluate the evaluation indicators by using fuzzy comprehensive evaluation method. Results: After two rounds of Delphi consultation questionnaire, the effective recovery rates were 80.0% and 90.0%, the expert authority levels were 0.89 and 0.86, the expert harmony coefficients for Kendall W were 0.166 and 0.310, and the variation coefficient of each index was <0.25. Finally, the evaluation index system of infectious disease prevention and control ability of colleges and universities included 4 first level indicators, 14 second level indicators and 75 third level indicators. The weights of prevention and monitoring and early warning, organizational system guarantee, emergency management, rehabilitation and summary were 0.176, 0.476, 0.268 and 0.080, respectively. The top 3 weights of the secondary indexes were 0.623 for infectious disease surveillance and early warning, 0.595 for loss assessment and 0.370 for emergency response. The score of fuzzy comprehensive evaluation of the index system of infectious disease prevention and control ability in colleges and universities was 79.148, suggesting a high level. Conclusion The established evaluation index system of infectious disease prevention and control ability in colleges and universities is scientific and reasonable, which is conducive to provide tool reference for the evaluation of infectious disease prevention and control ability in colleges and universities.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Alzheimer's disease （AD）， a degenerative disease of the central nervous system， is characterized by progressive degradation of learning， memory， and cognitive functions. Currently， few drugs are available for treating AD， and their effects are limited. Berberine （BBR） is a natural isoquinoline （quaternary ammonium-like） with a wide range of pharmacological effects. Studies have proven that BBR has good potential in the treatment of AD. Specifically， BBR can inhibit the generation， aggregation， and neurotoxicity of amyloid-β and the hyperphosphorylation of Tau protein， promote the clearance of phosphorylated Tau protein， reduce the cholinesterase activity， neuroinflammation， and oxidative stress， regulate neuronal apoptosis， improve the mitochondrial function and glucose and lipid metabolism， suppress the monoamine oxidase activity， and modulate gut microbiota. In addition， researchers have ameliorated the low bioavailability of BBR. Probing into the potential targets is hoped to provide a reference for further research on the prevention and treatment of AD by BBR.