Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

In recent years, the application of artificial intelligence (AI) in the field of biology has witnessed remarkable advancements. Among these, the most notable achievements have emerged in the domain of protein structure prediction and design, with AlphaFold and related innovations earning the 2024 Nobel Prize in Chemistry. These breakthroughs have transformed our ability to understand protein folding and molecular interactions, marking a pivotal milestone in computational biology. Looking ahead, it is foreseeable that the accurate prediction of various physicochemical properties of proteins—beyond static structure—will become the next critical frontier in this rapidly evolving field. One of the most important protein properties is thermodynamic stability, which refers to a protein’s ability to maintain its native conformation under physiological or stress conditions. Accurate prediction of protein stability, especially upon single-point mutations, plays a vital role in numerous scientific and industrial domains. These include understanding the molecular basis of disease, rational drug design, development of therapeutic proteins, design of more robust industrial enzymes, and engineering of biosensors. Consequently, the ability to reliably forecast the stability changes caused by mutations has broad and transformative implications across biomedical and biotechnological applications. Historically, protein stability was assessed via experimental methods such as differential scanning calorimetry (DSC) and circular dichroism (CD), which, while precise, are time-consuming and resource-intensive. This prompted the development of computational approaches, including empirical energy functions and physics-based simulations. However, these traditional models often fall short in capturing the complex, high-dimensional nature of protein conformational landscapes and mutational effects. Recent advances in machine learning (ML) have significantly improved predictive performance in this area. Early ML models used handcrafted features derived from sequence and structure, whereas modern deep learning models leverage massive datasets and learn representations directly from data. Deep neural networks (DNNs), graph neural networks (GNNs), and attention-based architectures such as transformers have shown particular promise. GNNs, in particular, excel at modeling spatial and topological relationships in molecular structures, making them well-suited for protein modeling tasks. Furthermore, attention mechanisms enable models to dynamically weigh the contribution of specific residues or regions, capturing long-range interactions and allosteric effects. Nevertheless, several key challenges remain. These include the imbalance and scarcity of high-quality experimental datasets, particularly for rare or functionally significant mutations, which can lead to biased or overfitted models. Additionally, the inherently dynamic nature of proteins—their conformational flexibility and context-dependent behavior—is difficult to encode in static structural representations. Current models often rely on a single structure or average conformation, which may overlook important aspects of stability modulation. Efforts are ongoing to incorporate multi-conformational ensembles, molecular dynamics simulations, and physics-informed learning frameworks into predictive models. This paper presents a comprehensive review of the evolution of protein thermodynamic stability prediction techniques, with emphasis on the recent progress enabled by machine learning. It highlights representative datasets, modeling strategies, evaluation benchmarks, and the integration of structural and biochemical features. The aim is to provide researchers with a structured and up-to-date reference, guiding the development of more robust, generalizable, and interpretable models for predicting protein stability changes upon mutation. As the field moves forward, the synergy between data-driven AI methods and domain-specific biological knowledge will be key to unlocking deeper understanding and broader applications of protein engineering.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

ObjectiveTo investigate the alleviating effect of calcium cyanamide （CaCN₂） soil fumigation on replanting problems of Rehmannia glutinosa. MethodsNewly soil （NP） was used as the control group， while three treatment groups were established： replanted soil （RP）， newly soil treated with CaCN₂ （120 g·m²， tillage depth 25 cm） （NPCC）， and replanted soil treated with CaCN₂ （RPCC）. R. glutinosa was cultivated in all groups. At harvest， the tuber agronomic traits （number of enlarged roots， maximum root diameter， fresh weight， dry weight） were measured. The content of catalpol and rehmannioside D was quantified by ultra-high-performance liquid chromatography （UPLC） to evaluate medicinal quality. Rhizosphere soil available nutrients and enzyme activities were analyzed by assay kits. The community structure and composition of fungi and bacteria in rhizosphere soil were assessed via internal transcribed spacer 2 （ITS2） sequencing and 16S rDNA sequencing， respectively. ResultsCompared with NP， the RP group showed obviously reduced in tuber agronomic traits and quality indicators （P0.05）. However， the RPCC group showed significant improvement in agronomic traits and a notable increase in rehmannioside D content compared to RP （P0.05）. The contents of available phosphorus and potassium in RPCC and NP groups were obviously lower than those in RP （P0.05）. The polyphenol oxidase soil （S-PPO） activity in RP was obviously lower than in NP （P0.05）， while sucrose soil （S-SC）， acid phosphatase soil （S-ACP）， and S-PPO activities in RPCC were obviously higher than in RP （P0.05）. Microbial richness and diversity in RP were obviously higher than in NP （P0.05）， whereas no significant differences were observed between the RPCC and NP. The relative abundances of fungal genera Nectria， Myrothecium， Tomentella， and bacterial genus Skermanella were obviousl lower in RPCC and NP than in RP （P0.05）. Correlation analysis that S-ACP activity was positively correlated with the content of rehmannioside D （P0.05）. Fungal genera Engyodontium and Alternaria， and bacterial genera Pir4 lineage， Pirellula， Methyloversatilis， Brevundimonas， Ralstonia， and Acidibacter were obviously positively correlated with tuber dry weight （P0.05）. Conversely， fungal genera Pseudaleuria， Nectria， Haematonectria， Ceratobasidium， and bacterial genera Streptomyces， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated with dry weight （P0.05）. The fungal genus Alternaria and bacterial genera Brevundimonas， Ralstonia， Acidibacter， and Dongia showed positive correlations with medicinal quality of R.glutinosa tuber， while fungal genera Pseudaleuria， Nectria， Stachybotrys， Fusarium， Gibberella， Ceratobasidium， and bacterial genera Sphingomonas， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated （P0.05）. ConclusionCaCN₂ soil fumigation can significantly improve enzyme activities in replanted Rehmannia rhizosphere soil， enhance the utilization of available nutrients， reshape microbial community structure of replanted R.glutinosa at the family and genus level， and notably improve tuber agronomic traits and medicinal quality. This study provides a novel approach to alleviating replanting problems and offers insights for the integrated development of standardized cultivation techniques， including soil disinfection， nutrient-targeted regulation， and microbial inoculant application.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Objective To summarize the acupoints and parameters commonly used in the treatment of vascular cognitive impairment(VCI)by electro-acupuncture(EA)through the visual data mining technique to provide a reference basis for clinical treatment.Methods The clinical studies of EA on the treatment of VCI were searched in CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases.The literature is managed by Note Express and the database is established by Excel.The frequency of selected acupoints,frequency,meridian tropism,parameter frequency and frequency of used acupoints are counted.Factor analysis is carried out by SPSS 21.0 software.SPSS Modeler 18.3 software is used to analyze association rules and co-occurrence network,and the analysis results are visualized by Cytoscape 3.9.1 software.Results Finally,155 papers were included,containing 155 acupoint prescriptions and 157 parameter prescriptions.Acupoint prescriptions involved 100 acupoints with a total frequency of 856 times;parameter prescriptions involved 33 parameters with a total frequency of 788 times.Conclusion At present,there is a big difference between the clinical studies,and there is no recognized acupoint and parameter for EA treatment of VCI.By further summarizing the law of EA acupuncture point and parameter,the study has sorted out the law of commonly used acupoints,meridian tropism,compounding and parameter selection for EA treatment of VCI.It was concluded that the selection of acupoints mainly started from the three aspects of deficiency,phlegm and stasis,focusing on the combination of local and distal selection of acupoints,through the identification of internal organs and meridians,to achieve the simultaneous regulation of the heart,spleen and kidney,and to take into account both the symptoms and the root cause,and to play the roles of opening the orifices to wake up mind,calming mind and benefiting intellect,strengthening the spleen and tonifying the kidneys,and invigorating blood circulation to remove stasis.The parameters of EA are recommended to be sparse and dense wave,low frequency,as tolerated by the patient,30 minutes/times,1 time/day,5 times/week as the main combinations,which can provide a certain reference basis for clinical decision-making.

Objective To evaluate the clinical effect of total optic nerve canal decompression in the treatment of traumatic optic neuropathy(TON)without photoreceptor.Methods The clinical data of 67 patients with no photoreceptor TON admitted to Department of Neurosurgery of the Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine from January 2015 to December 2021 were selected for retrospective analysis,in which 37 cases in observation group received total optic nerve canal decompression surgery and 30 cases in control group received non-total optic nerve canal decompression surgery.Both groups received high-dose glucocorticoid therapy and oral administration of methylcobalamin before surgery.The visual acuity changes and complications after admission and treatment were examined and recorded in both groups.The effective rate,unblinding rate and complications after treatment were compared between the two groups.Results There were no statistically significant differences between observation group and control group in terms of age,gender,time from injury to surgery,preoperative GCS score,operative time,and intraoperative bleeding volume(P>0.05).After treatment,the effective rate of observation group was 54.1%and the unblinding rate was 35.1%,while the effective rate of control group was 46.7%and the unblinding rate was 33.3%;there was no statistically significant difference between the effective rate and unblinding rate of the two groups(P>0.05).No serious complications such as cerebrospinal fluid leakage,epilepsy,and intracranial infection occurred in both groups after surgery.In observation group,the effective rate after treatment was significantly lower in those with optic nerve canal fractures than that in those without optic nerve canal fractures(P<0.05);the effective rate was significantly higher in patients with injury-to-operation time≤7 d than that in patients with injury-to-operation time>7 d(P<0.05).Conclusion Total optic nerve canal decompression can improve the visual acuity of patients without photoreceptor TON and reduce the blinding rate,which is an effective surgical treatment method.

BACKGROUND:In the initial stage of multiple sclerosis,central immune cells activate and release a large number of inflammatory factors,causing white matter demyelination and even involving gray matter neurons.The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis.The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice,and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE:To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS:Female C57BL/6 mice were divided into the normal control group,experimental autoimmune encephalomyelitis disease model group,and astragaloside IV treatment group(n=8 per group).Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups.On day 10 to 28 after immunization,the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically.Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day.On the 28th day after immunization,the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord.Percentage of splenic T cell subsets was detected using flow cytometry.Western blot assay was used to determine the protein expression of interferon-γ,interleukin-17 and interleukin-6 in the spinal cord.Levels of interferon-γ,interleukin-17,interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION:(1)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice(P<0.05),ameliorate clinical symptoms(P<0.05),inhibit the infiltration of inflammatory cells and alleviate myelin loss(P<0.01,P<0.05).(2)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could inhibit the proportion of CD4+T cell subsets expressing interferon-γ(P<0.001)and interleukin-17(P<0.001),but increase percentages of CD4+ interleukin-10+(P<0.001)and CD4+ transforming growth factor-β+(P<0.01)T cell subsets.(3)Astragaloside IV could inhibit the expression of interferon-γ(P<0.05,P<0.01),interleukin-17(P<0.05,P<0.05),and interleukin-6(P<0.05,P<0.05)in the spinal cord and spleen,and up-regulate the expression of interleukin-4(P<0.01)in spleen.(4)These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice,which may be related to regulating the splenic T cell subsets,therefore,inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination.