ObjectiveThis Study was conducted to investigate the interaction mechemisms between gutmicrobiota dysregulation and ischemic stroke by establishing a rat model of ischemic stroke and employing fecal microbiota transplantation (FMT). MethodsA preliminary experiment was conducted to establish an antibiotic-induced pseudo-sterile (ABX) rat model through antibiotic treatment, and a cerebral ischemia model was prepared using the middle cerebral artery occlusion (MCAO) method. Fecal microbiota from stroke patients and healthy individuals were transplanted via FMT, followed by behavioral testing. 16S rRNA sequencing was used to analyze the microbial community, hematoxylin and eosin (HE) staining to observe histopathological status, transmission electron microscopy (TEM) to examine the tight junction structure of the small intestine, and enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory factors and intestinal barrier-related markers. Results16S rRNA sequencing of fecal samples showed that compared with the normal control group and the metronidazole group, the abundance and diversity of fecal microorganisms in the quadruple antibiotic group were significantly reduced, indicating successful establishment of the ABX model. After transplanting fecal microbiota from stroke patients into ABX rats, significant changes in gut microbiota composition were observed. Behavioral tests revealed that the MCAO model group showed significant decreases in both horizontal movement and vertical exploration abilities. ELISA results indicated that IL-17 concentration in the ABX+mFMT (antibiotic-treated+model fecal microbiota transplantation) group was lower than in the ABX+cFMT (antibiotic-treated+control fecal microbiota transplantation) group, suggesting that IL-17 may serve as a key inflammatory indicator for evaluating the impact of stroke intervention on gut microbiota. Triphenyltetrazolium chloricle staining (TTC) staining suggested that gut microbiota intervention may increase the risk of stroke. HE staining showed that, except for the control group, all groups exhibited ischemic changes and inflammatory infiltration in brain tissues. TEM revealed that microvilli of small intestinal epithelial cells in the ABX+mFMT group were sparser than those in the ABX+cFMT group, indicating that microbial intervention affects intestinal barrier function. ConclusionThe ABX model established using broad-spectrum antibiotics showed no significant differences in physiological characteristics compared to normal rats, and the findings were consistent with those from germ-free rat models. Stroke prognosis appears to be influenced by intestinal dysbiosis, accompanied by significantly elevated levels of the pro-inflammatory cytokine IL-17, which may exacerbate neural injury via the gut-brain axis. Behavioral experiments indicated that transplantation of gut microbiota from stroke rats impaired cognitive function. Furthermore, IL-17 demonstrated sensitivity to alterations in the gut microbiota, suggesting its potential as a key therapeutic target for stroke intervention.

ObjectiveThis Study was conducted to investigate the interaction mechemisms between gutmicrobiota dysregulation and ischemic stroke by establishing a rat model of ischemic stroke and employing fecal microbiota transplantation (FMT). MethodsA preliminary experiment was conducted to establish an antibiotic-induced pseudo-sterile (ABX) rat model through antibiotic treatment, and a cerebral ischemia model was prepared using the middle cerebral artery occlusion (MCAO) method. Fecal microbiota from stroke patients and healthy individuals were transplanted via FMT, followed by behavioral testing. 16S rRNA sequencing was used to analyze the microbial community, hematoxylin and eosin (HE) staining to observe histopathological status, transmission electron microscopy (TEM) to examine the tight junction structure of the small intestine, and enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory factors and intestinal barrier-related markers. Results16S rRNA sequencing of fecal samples showed that compared with the normal control group and the metronidazole group, the abundance and diversity of fecal microorganisms in the quadruple antibiotic group were significantly reduced, indicating successful establishment of the ABX model. After transplanting fecal microbiota from stroke patients into ABX rats, significant changes in gut microbiota composition were observed. Behavioral tests revealed that the MCAO model group showed significant decreases in both horizontal movement and vertical exploration abilities. ELISA results indicated that IL-17 concentration in the ABX+mFMT (antibiotic-treated+model fecal microbiota transplantation) group was lower than in the ABX+cFMT (antibiotic-treated+control fecal microbiota transplantation) group, suggesting that IL-17 may serve as a key inflammatory indicator for evaluating the impact of stroke intervention on gut microbiota. Triphenyltetrazolium chloricle staining (TTC) staining suggested that gut microbiota intervention may increase the risk of stroke. HE staining showed that, except for the control group, all groups exhibited ischemic changes and inflammatory infiltration in brain tissues. TEM revealed that microvilli of small intestinal epithelial cells in the ABX+mFMT group were sparser than those in the ABX+cFMT group, indicating that microbial intervention affects intestinal barrier function. ConclusionThe ABX model established using broad-spectrum antibiotics showed no significant differences in physiological characteristics compared to normal rats, and the findings were consistent with those from germ-free rat models. Stroke prognosis appears to be influenced by intestinal dysbiosis, accompanied by significantly elevated levels of the pro-inflammatory cytokine IL-17, which may exacerbate neural injury via the gut-brain axis. Behavioral experiments indicated that transplantation of gut microbiota from stroke rats impaired cognitive function. Furthermore, IL-17 demonstrated sensitivity to alterations in the gut microbiota, suggesting its potential as a key therapeutic target for stroke intervention.

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.

Wilson disease （WD） is an autosomal recessive disorder of copper metabolism， and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine （TCM） and points out that abnormal natural endowment is the core etiology and pathogenesis of WD， with internal accumulation of copper toxicity as the manifestation， liver/spleen/kidney dysfunction as the root cause， and intermingled “toxin， stasis， phlegm， and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD， including stagnation of liver Qi， internal retention of damp-heat， phlegm-stasis-heat accumulation syndrome， liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency， and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM， thereby giving full play to the advantages of TCM in the treatment of this disease.

ObjectiveTo investigate the potential mechanism of Danggui Buxuetang （DBT） in the treatment of vascular dementia （VAD）. MethodsSixty male SD rats were randomly assigned to the sham-operated group， model group， DBT low-， medium-， and high-dose groups， and the donepezil group. Except for the sham-operated group， rats in all other groups underwent bilateral common carotid artery ligation. After successful modeling， DBT was administered at doses of 9.2， 18.4， 36.8 g·kg^-1 for the low-， medium-， and high-dose groups， respectively， while the donepezil group received 3 mg·kg^-1 donepezil solution by gavage once daily. After 4 consecutive weeks of drug treatment， rats underwent the Morris water maze test， novel object recognition test， Nissl staining to observe hippocampal neurons， and immunofluorescence staining to detect the expression of neuronal nuclear protein （NeuN） in the hippocampus. Western blot was used to assess the expression of PTEN-induced kinase 1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Transmission electron microscopy was used to observe hippocampal neuronal ultrastructure. Real-time PCR was used to detect the expression of NADPH oxidase subunits p22^phox and p47^phox in hippocampal tissues. The levels of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， and total antioxidant capacity were measured to evaluate oxidative stress levels. ResultsIn the Morris water maze test， escape latency changed significantly over time in all groups except the model group. Compared with the sham-operated group， the model group showed significantly prolonged escape latency （P<0.01）. Compared with the model group， rats in the DBT groups and the donepezil group exhibited significantly shorter escape latency （P<0.05， P<0.01）. The number of crossings over the original platform was significantly reduced in the model group compared with the sham-operated group （P<0.01）， whereas rats in the DBT and donepezil groups showed significantly increased platform crossings compared with the model group （P<0.05， P<0.01）. Compared with the sham-operated group， exploration time of new objects was significantly reduced in the model group （P<0.01）. Compared with the model group， exploration time of new objects increased significantly in the medium- and high-dose DBT groups and the donepezil group （P<0.05， P<0.01）， while no significant change was observed in the low-dose DBT group. Compared with the high-dose DBT group， rats in the donepezil group had significantly prolonged escape latency and reduced platform crossings and new-object exploration time （P<0.05）. Nissl staining showed decreased density of healthy neurons in the CA1 and CA3 regions of the hippocampus in the model group， with loss of Nissl bodies and nuclear atrophy or disappearance. In the high-dose DBT group， neuronal density in CA1 and CA3 increased， with neurons arranged closely and displaying normal morphology. Immunofluorescence showed that compared with the sham-operated group， the hippocampal NeuN⁺ cell count in the VAD model group was significantly decreased（P<0.01）， compared with the VAD model group， the hippocampal NeuN⁺ cell count in the high-dose DBT group was significantly increased（P<0.01）. Compared with the sham-operated group， the expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins was significantly increased（P<0.01）， while the expression of Bcl-2 was significantly decreased in the VAD model group（P<0.01）. Compared with the VAD model group， the high-dose DBT group showed significantly decreased expression of PINK1， Parkin， LC3Ⅱ， and Bax proteins（P<0.01）and significantly upregulated Bcl-2 expression（P<0.01）. The medium-dose DBT group exhibited significantly reduced expression of Parkin， LC3Ⅱ， and Bax proteins（P<0.05，P<0.01） and significantly increased Bcl-2 expression（P<0.01）， while no statistically significant differences were observed in the low-dose DBT group. Transmission electron microscopy showed mitochondrial pyknosis， thickened cristae， increased electron density， and the presence of mitochondrial autophagy in the model group. In contrast， hippocampal neurons in the high-dose DBT group contained abundant mitochondria with intact morphology， clear cristae， and uniform matrix. Compared with the sham-operated group， total antioxidant capacity， SOD activity， and GSH levels were significantly decreased， while MDA levels were significantly increased in the model group （P<0.01）. Compared with the model group， total antioxidant capacity and antioxidant levels （SOD， GSH） increased significantly， and MDA decreased significantly in the medium- and high-dose DBT groups （P<0.01）， while no significant changes were observed in the low-dose DBT group. Compared with the sham-operated group， mRNA expression of p22^phox and p47^phox was significantly increased in the model group （P<0.01）. Compared with the model group， expression of p22^phox and p47^phox was significantly decreased in the DBT groups （P<0.05， P<0.01）. ConclusionDBT may exert neuroprotective effects by regulating PINK1/Parkin-mediated mitochondrial autophagy， thereby improving learning and memory abilities and treating VAD.

Objective: To analyze the process of handling a pulmonary tuberculosis(TB) outbreak among senior high school students in a boarding school in Chongqing, as well as to investigate the underlying causes of the outbreak, so as to provide evidence to inform TB prevention and control strategies in school settings. Methods: From November 2023 to April 2024, an epidemiological investigation was conducted into the TB outbreak in a grade 12 class from a boarding high school. Suspected cases were screened using symptom screening, tuberculin skin test (TST), and chest X-ray examinations. Confirmed cases underwent individual epidemiological interviews and sputum culture; Cultured positive mycobacterial strains were subjected to whole genome sequencing after identification as Mycobacterium tuberculosis. Results: A total of 10 active pulmonary TB cases were identified, all from the same class, yielding a student attack rate of 16.67%. Three isolates were culture positive, as well as all strains were of L2 type，and the WGS analysis of the strains suggested a common transmission chain. Excluding the index case, four additional cases were detected through symptom driven health care visits. Notably, 70% of patients presented with "chest tightness and chest pain" symptoms, and 50% had "cough" symptoms,but none were detected during morning health checks or tracking of absences due to illness. A total of 326 contacts were identified and underwent three rounds of screening and one follow up examination. In the initial screening, 35 close contacts from the same class showed strong TST positivity, corresponding to a strong positivity rate of 55.56%, significantly higher than the 20.76% observed among casual contacts ( χ 2=29.80, P <0.01). Among the 35 strongly TST positivvity close contacts and five individuals with moderate TST positivity whose induration had increased by ≥10 mm over two years, none received timely preventive treatment initially; five of them were subsequently diagnosed with active TB within three months. Following this, 25 individuals initiated preventive therapy, resulting in a preventive treatment initiation rate of 62.50%. Among TST negative classmates who converted to strong positivity on repeat TST testing at three months, 75.00% started preventive treatment, but only 22.22% completed the full course. Conclusion Inadequate implementation of morning health checks and cause tracking for absenteeism due to illness, poorly standardized screening procedures, and delayed preventive treatment may have been key factors contributing to the spread of the outbreak.

To investigate the distribution and development of common allergens in children in Hangzhou area, and to provide an epidemiological basis for the prevention, diagnosis, and treatment of allergic diseases in this area. This study is a retrospective study, selecting 3 524 children who underwent allergen screening at DiAn Medical Laboratory Center (Hangzhou) Co., Ltd. from January 2022 to January 2024 as the research subjects, including 2 012 males and 1 512 females. Among them, there were 1 098 infants (0-1 year olds), 1 673 toddlers (1-3 year olds), and 753 children (3-14 year olds). Immunoblotting was used to detect 21 allergen-specific immunoglobulin E (sIgE) antibodies. The positive rates of various allergens were calculated according to gender, age, and other factors, and the epidemiological characteristics and trends were analyzed. The results showed that the overall positive rate of sIgE was 60.33% (2 126/3 524). The main inhaled allergens were Dermatophagoides pteronyssinus/Dermatophagoides farinae (992, 28.15%), dog dander (295, 8.37%) and cat dander (181, 5.13%). The main food allergens were milk (696, 19.75%), egg white (541, 15.36%) and shrimp (205, 5.83%). Boys had significantly higher sIgE positivity rates than girls for Dermatophagoides pteronyssinus/Dermatophagoides farinae(642, 31.90%, χ2=10.10, P=0.001), house dust(61, 3.02%, χ2=5.12, P=0.024), cat dander(124, 6.16%, χ2=4.06, P=0.044), mold combinations(103, 5.14%, χ2=7.51, P=0.006), and tree pollen combinations(42, 2.07%, χ2=5.44, P=0.020) (all P<0.05); With age, there was a significant increase in positivity rates for house dust mite/dust mite, house dust, mold combinations, milk, and beef (all P<0.05), and a significant decrease in positivity rates for cockroach consumption, egg whites, shrimp, crab, cod, lobster/scallop, and soybeans (all P<0.05), the positive rates of only ingestive allergens decreased significantly ( P<0.001), and the positive rates of only inhalant and mixed allergens increased significantly ( P<0.001). In conclusion,in the Hangzhou area, dust mites are the most common inhalant allergens among children with allergic diseases, while milk is the most common food allergen. Boys are more sensitive to inhalant allergens, and as children grow older, the positive rates for different allergens undergo significant changes. Dynamic monitoring of changes in specific IgE antibodies to various allergens can assist in the diagnosis, prevention, and treatment of allergic diseases.

AIM To investigate effects of petroleum ether fraction from Derris eriocarpa How on glucose and lipid metabolism in a mouse model of metabolic syndrome(MS).METHODS KM mice were fed a high-fat diet and administered streptozotocin intraperitoneally to establish MS models.The MS mice were then randomly assigned to the model group,the metformin hydrochloride group,the lovastatin group,the ursolic acid group,and the high-,medium-and low-dose D.eriocarpa petroleum ether fraction groups,with 10 mice in each group.Ten additional mice maitained on a normal diet served as the normal control group.After 4 weeks of intragastric administration,glucose and lipid metabolism indicators were measured.Hepatic pathological changes were assessed using HE staining and oil red O staining.Liver tissue mRNA expressions of ATF3,PEPCK,FXR,CYP7A1,HNF4ɑ,CYP8B1 and SRB1 were quantified by RT-qPCR.Hepatic protein expressions of ATF3,HNF4ɑ,PEPCK,FXR and CYP7A1 was analyzed by Western blot in MS mice.RESULTS Compared to the model group,the high-dose D.eriocarpa petroleum ether fraction group exhibited significant glucose tolerance improvement(reduced OGTT-AUC,P＜0.01);favorable serum lipid modulation in terms of increased HDL-C levels(P＜0.01)and decreased TG,TC,LDL-C(P＜0.01);reduced renal biomarkers(BUN,SCR)and hepatotoxic indicators of TBA,AST and ALT activities(P＜0.01);alleviated hepatic lipid accumulation and histopathological damage;downregulated mRNA and protein expressions of ATF3,HNF4ɑ and PEPCK,as well as CYP8B1 mRNA expression(P＜0.01);and upregulated mRNA and protein expressions of FXR and CYP7A1,along with SRB1 mRNA expression(P＜0.01).CONCLUSION D.eriocarpa petroleum ether fraction ameliorates glucose and lipid metabolism dysregulation in MS mice by modulating the ATF3/HNF4ɑ/CYP7A1 signaling pathway,consequently eliciting hypoglycemic,hypolipidemic,hepatoprotective and nephroprotective effects.

Objective:To evaluate the service capability and operational efficiency of surgical departments in a hospital using data analysis models such as entropy weight TOPSIS and Boston matrix analysis, for references for optimizing medical resource allocation, promoting refined management and sustainable development of the hospital.Methods:The operational data of 24 surgical departments (A~X) in a tertiary public hospital in 2023 from its information system were extracted. The number of doctors, actual number of open beds, and average length of stay etc., were served as evaluation indicators. The TOPSIS and rank sum ratio methods were used to evaluate the medical service capabilities, the data envelopment analysis (DEA) was used to analyze operational efficiency, and Boston matrix analysis was used for departmental classification.Results:In terms of medical service capabilities, the top 5 departments were F, S, K, D, and C ( Ci>0.41), all of which were in the excellent category; The bottom three departments were L, N, and G ( Ci<0.04), all of which were in the poor range. From the perspective of operational efficiency, 8 departments had achieved strong DEA effectiveness, while the remaining 16 departments were non DEA effective, resulting in resource redundancy or insufficient output. According to the Boston Matrix analysis, 8 departments (stars) had strong medical service capabilities and high operational efficiency; 6 departments (cash cows) had poor medical service capabilities but high operational efficiency, and 8 departments (dogs) had poor medical service capabilities and operational efficiency; 2 departments (question marks) had strong medical service capabilities but low operational efficiency. Conclusions:This study comprehensively applied multiple data models to objectively and comprehensively evaluate the service capabilities and operational efficiency of surgical departments. Hospitals could develop corresponding resource allocation optimization strategies based on the Boston matrix classification results, combined with the disease characteristics and business scale configuration of each department.

OBJECTIVE To investigate the risk factors for biliary tract infection(BTI)after biliary drainage in pa-tients with obstructive jaundice(OJ)based on clinical characteristics and biliary drainage methods,and to con-struct and validate a nomogram model for risk prediction.METHODS A total of 168 patients with OJ treated in the Hepatobiliary Surgery Department of Ningbo Municipal Hospital of TCM from Jan.2020 to Jan.2025 were includ-ed as study subjects.They were divided into a non-infected group(n=97)and an infected group(n=71)based on the occurrence of BTI after biliary drainage.Lasso regression and logistic regression analysis were used to explore the risk factors for BTI after surgery in patients with OJ.The"rms"package in R programming language version 4.2.6 was used to construct the nomogram model,and decision curves,calibration curves and receiver operating characteristic(ROC)curves were plotted to evaluate the model's effectiveness,calibration and discrimination.RESULTS Diabetes history(OR=3.314),drainage method(percutaneous transhepatic cholangial drainage,OR=2.666),preoperative jaundice duration(OR=2.920),alkaline phosphatase(OR=1.064),total bilirubin(OR=1.028),NLR(OR=1.110)and high biliary obstruction(OR=4.770)were identified as risk factors for BTI after surgery in patients with OJ(P＜0.05).The importance of these risk factors,ranked by the feature_importances_function of the logistic regression model,was as follows:high biliary obstruction,drainage method,preoperative jaundice duration,diabetes history,NLR,total bilirubin and alkaline phosphatase.Based on these seven risk fac-tors,a nomogram model for predicting BTI risk after surgery in patients with OJ was constructed.The area under the ROC curve(AUC)of the model was 0.851,with a concordance index of 0.849.The decision curve suggested that the model had good predictive performance within a probability threshold range of 0.050 to 0.920.The calibra-tion curve of the model closely aligned with the ideal curve.CONCLUSIONS The risk factors for BTI after surger-y in patients with OJ include diabetes history,drainage method,preoperative jaundice duration,alkaline phospha-tase,total bilirubin,NLR and high biliary obstruction.The constructed nomogram model for predicting BTI after surgery in patients with OJ demonstrates good predictive performance.