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.

ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pathway and epithelial-mesenchymal transition （EMT） in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a prednisone acetate group （1.17 mg·kg^-1）， and low- and high-dose Yifei Tongluo prescription groups （10.62 and 21.24 g·kg^-1， respectively）. Administration started on the 7th day after modeling， once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression of α-smooth muscle actin （α-SMA） and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome， E-cadherin （E-cad）， and typeⅠ collagen （ColⅠ） in lung tissues was detected by immunofluorescence. The content of hydroxyproline （HYP）， tumor necrosis factor （TNF）-α， interleukin （IL）-18， and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β， and transforming growth factor （TGF）-β₁ in rat lung tissues were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NLRP3， GSDMD， ASC， and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group， the model group exhibited a significantly increased lung coefficient （P<0.01） and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition， the levels of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissues were significantly increased （P<0.01）. The levels of fibrosis- and inflammation-related factors HYP， TNF-α， IL-18， and IL-1β in serum were significantly upregulated （P<0.01）. The levels of factors related to the activation of NLRP3 inflammasome in lung tissues， including NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁， were significantly upregulated （P<0.01）. Compared with the model group， the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally， the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissue was significantly decreased （P<0.01）. The levels of HYP， TNF-α， IL-18， and IL-1β in serum were significantly reduced （P<0.01）. The expression levels of NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β₁ in lung tissue were also significantly decreased （P<0.01）. ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway， down-regulate release of pro-inflammatory and pro-fibrotic cytokines， alleviate NLRP3 inflammasome-mediated pyroptosis and EMT， and thereby improve pulmonary fibrosis in rats.

BACKGROUND:Cellular senescence,which triggers the aging process of physiological decline in the body,is closely related to osteoporosis.With the development of aging research,significant progress has been made in the study of targeted clearance of senescent cells.Accordingly,senolytic cell therapy for osteoporosis based on this has attracted increasing attention.Current research on the association between aging and osteoporosis shows the characteristic of multidisciplinary intersection.However,existing reviews are mostly based on a single database(such as PubMed)and lack a systematic comparative analysis of Chinese and English literature.Therefore,it is of great academic value to integrate resources from multiple databases and systematically reveal the research status and hot trends of aging in the field of osteoporosis research.OBJECTIVE:To summarize the development,current status,hotspots,and future trends of research on aging in the field of osteoporosis over the past 20 years,so as to provide references for future related research.METHODS:We searched for research literature on the correlation between aging and osteoporosis in CNKI,WanFang,VIP and Web of Science Core Database.The search time span was from August 1,2004 to September 24,2024.Then,we used NoteExpress 4.0 for data cleaning and CiteSpace 6.3R1(Advanced)and Excel(2024)for literature analysis.RESULTS AND CONCLUSION:Since 2004,research on the correlation between aging and osteoporosis has shown a significant growth trend.Bibliometric analysis shows that(as of September 2024),and 1 275 English documents and 151 Chinese documents have been published,with the highest number of publications in China and the United States.In terms of publishing institutions,the Mayo Clinic ranked first,followed by Shanghai Jiao Tong University and the University of California system.As for core authors,Sundeep Khosla and Joshua Nicholas Farr were the authors with the most publications and citations,while Pei Lingpeng and Hui Bodi were the most worthy of attention in Chinese literature.After the keywords"aging"and"osteoporosis"and their synonyms were excluded,it was found that cellular senescence,senescence-associated secretory phenotype,signaling pathways,and targeted senolytic cell clearance therapy haven been the current research hotspots and theoretical frontiers.

BACKGROUND:Cellular senescence,which triggers the aging process of physiological decline in the body,is closely related to osteoporosis.With the development of aging research,significant progress has been made in the study of targeted clearance of senescent cells.Accordingly,senolytic cell therapy for osteoporosis based on this has attracted increasing attention.Current research on the association between aging and osteoporosis shows the characteristic of multidisciplinary intersection.However,existing reviews are mostly based on a single database(such as PubMed)and lack a systematic comparative analysis of Chinese and English literature.Therefore,it is of great academic value to integrate resources from multiple databases and systematically reveal the research status and hot trends of aging in the field of osteoporosis research.OBJECTIVE:To summarize the development,current status,hotspots,and future trends of research on aging in the field of osteoporosis over the past 20 years,so as to provide references for future related research.METHODS:We searched for research literature on the correlation between aging and osteoporosis in CNKI,WanFang,VIP and Web of Science Core Database.The search time span was from August 1,2004 to September 24,2024.Then,we used NoteExpress 4.0 for data cleaning and CiteSpace 6.3R1(Advanced)and Excel(2024)for literature analysis.RESULTS AND CONCLUSION:Since 2004,research on the correlation between aging and osteoporosis has shown a significant growth trend.Bibliometric analysis shows that(as of September 2024),and 1 275 English documents and 151 Chinese documents have been published,with the highest number of publications in China and the United States.In terms of publishing institutions,the Mayo Clinic ranked first,followed by Shanghai Jiao Tong University and the University of California system.As for core authors,Sundeep Khosla and Joshua Nicholas Farr were the authors with the most publications and citations,while Pei Lingpeng and Hui Bodi were the most worthy of attention in Chinese literature.After the keywords"aging"and"osteoporosis"and their synonyms were excluded,it was found that cellular senescence,senescence-associated secretory phenotype,signaling pathways,and targeted senolytic cell clearance therapy haven been the current research hotspots and theoretical frontiers.

ObjectiveTo screen suitable packaging and storage conditions for small packaged Alismatis Rhizoma decoction pieces， laying the foundation for developing standardized storage， maintenance techniques and determining shelf life. MethodsUsing the accelerated stability test method， the small packaged decoction pieces of Alismatis Rhizoma were placed in polyethylene plastic bags， aluminum foil polyethylene composite bags， and cowhide coated paper bags under temperature of （40±2） ℃ and relative humidity of （75±5）% conditions， the quality testing was conducted at the end of the 0^th， 1^st， 2^nd， 3^rd， and 6^th month， respectively. Using long-term stability test method， an orthogonal experiment was designed to investigate storage conditions， packaging materials， and packaging methods. At the end of the 0^th， 1^st， 3^rd， 6^th， 9^th， 12^th， 18^th， and 24^th month， the quality of small packaged Alismatis Rhizoma decoction pieces was tested under different packaging and storage conditions（including 2 packaging methods：vacuum packaging and sealed packaging， 3 storage conditions：room temperature， cool， and modified atmosphere， 3 packaging materials：cowhide coated paper bag， aluminum foil polyethylene composite bag， and polyethylene plastic bag）. Then， the G1-entropy weight method combined with orthogonal experiment was used to analyze the quality changes of the decoction pieces under different packaging and storage conditions to identify optimal packaging and storage conditions. The quality testing indicators for Alismatis Rhizoma decoction pieces were expanded beyond those specified in the 2020 edition of the Pharmacopoeia of the People's Republic of China. In addition to the existing indicators（characteristics， moisture content， extractives， and the total content of 23-acetyl alisol B and 23-acetyl alisol C）， new indicators including color value， water activity， total triterpenoid content， and alisol B content have been added. ResultsThe accelerated stability test results indicated that the quality of small packaged Alismatis Rhizoma decoction pieces was more stable when packaged in aluminum foil-polyethylene composite materials compared to cowhide-coated paper bags and polyethylene plastic bags. Analysis of the long-term stability test results using the G1-entropy weight method combined with orthogonal experiment revealed that storage conditions had the greatest impact on both raw and salt-processed products， followed by packaging materials， while the packaging method had the least influence. For both types of small packaged Alismatis Rhizoma decoction pieces， modified atmosphere storage demonstrated superior efficacy compared to cool storage or room temperature storage. Storage in aluminum foil-polyethylene composite bags was superior to polyethylene plastic bags or cowhide-coated paper bags. However， the stability of sealed raw products was better than vacuum-packed ones， whereas vacuum-packed salt-processed products exhibited greater stability than their sealed counterparts. ConclusionBased on the results of the quality changes of small packaged Alismatis Rhizoma decoction pieces under different storage conditions， it is recommended that the suitable storage packaging conditions for small packaged raw products are sealed packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage， and the suitable storage and packaging conditions for small packaged salt-processed products are vacuum packaging with aluminum foil polyethylene composite bags and controlled atmosphere storage.

OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

Polycystic ovary syndrome（PCOS） and its resulting infertility is one of the common diseases of gynecology and reproductive endocrinology. The phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway is relatively well-studied in the development of intervention in PCOS， and the experiments on PCOS in rats conducted by traditional Chinese medicine through this signaling pathway is also the main direction of mechanistic research. In this paper， 20 articles published in academic journals in the past 5 years were selected through the corresponding criteria， and the objective situation and existing problems of the selected research projects were analyzed from five aspects， namely， baseline data， modeling and treatment， grouping， evaluative indexes， and pharmacodynamic indexes. It is found that there were different degrees of problems in each research project， such as the observation indicators of modeling， criteria for judging the success of the model， the treatment period， the calculation of dosage of prescription/active ingredients and specific dosage were not clearly defined， which could easily lead the bias of the results or reduce the validity of experimental data. Based on this， the list of PCOS rat experimental research operations was formed， involving five categories of experimental rats， model construction， study implementation， outcome measures and analysis and report with a total of 21 operation lists， with a view to provide a reference for the subsequent PCOS experiments related to scientific research and helping to form high-quality results.

Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

Purpose To investigate the role of secreted protein acidic and rich in cysteine(SPARC)expression in the diagnosis and differential diagnosis of mesothelioma.Methods Immunohistochemical EnVision two-step method was used to detect SPARC expression in 40 cases of mesothelioma,4 cases of well-differentiated mesothelial tumour(WDPMT),40 cases of poorly differentiated squamous cell carcinoma of the lung,40 cases of poorly differentiated ad-enocarcinoma of the lung,20 cases each of low-grade and high-grade serous carcinoma of the ovary.The sensitivity and specificity of SPARC,Calretinin,D2-40,and WT-1 expression in mesothelioma were compared and analyzed.Results SPARC showed diffuse strong positive expression in mesothelioma(37/40 cases),medium positive expression in WDPMT(3/4 cases),and focal weak positive expression in a few cases of poorly differentiated squamous cell carcino-ma of the lung(1/40 cases),poorly differentiated adenocarcinoma of the lung(2/40 cases),low-grade serous carci-noma of the ovary(0/20 cases),and high-grade serous carcinoma of the ovary(1/20 cases).In 40 mesotheliomas,the sensitivity of SPARC was 92.5％,and the specificity of SPARC in control tumors(squamous carcinoma of the lung,adenocarcinoma of the lung,and serous carcinoma of the ovary)was 96.7％.Conclusion SPARC is widely expressed in mesotheliomas,with a sensitivity similar to that of Calretinin,D2-40,and WT-1,but with a much higher specificity than other mesothelial markers.It is of great significance in distinguishing between mesothelioma and pulmo-nary poorly differentiated carcinoma and ovarian serous carcinoma.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.