Pulmonary hypertension (PH), marked by sustained elevation of pulmonary artery pressure, imposes a heavy burden on the right ventricle and may culminate in right heart failure. Its pathogenesis is multifaceted, encompassing endothelial dysfunction, vascular smooth muscle proliferation, inflammation, thrombosis, and genetic factors. Animal models serve as core tools for exploring PH mechanisms and therapies, each with unique strengths and limitations. The single-dose monocrotaline (MCT) model is one of the most commonly used experimental animal models of PH and is widely applied in mechanistic studies, drug screening, and efficacy evaluation; it offers simplicity and cost-effectiveness, can induce PH within a short period, yet its pathophysiology differs to some extent from human idiopathic PH. In contrast, the Sugen5416 combined with chronic hypoxia model better mimics PH progression by placing animals under hypoxic conditions to induce pulmonary vasoconstriction and vascular remodeling, but it requires a longer modelling time, and the degree of hypoxia has a substantial impact on experimental outcomes. Beyond these two commonly used modeling approaches, a variety of emerging techniques have been applied in PH research; gene-editing technologies enable precise investigation of specific gene functions in PH. Additionally, induced pluripotent stem cell-based 3D organoid technology allows for individualized modelling while preserving patients' genetic information for precise clinical translation. Each model or technology can simulate different aspects of the pathological processes of human PH, and their findings provide key insights into the nature of the disease and serve as an important platform for the development of novel therapeutic targets. This paper comprehensively describes various animal models and emerging technologies used in PH research, analyzing their characteristics, applications, and limitations, with the aim of providing experimental and technical support for the development of new therapeutic strategies and drugs.

OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

ObjectiveTo systematically sort out literatures regarding telemedicine, wearable devices and artificial intelligence in pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) from 2011 to 2025, to identify the research status, hotspots and development trends. MethodsOriginal articles and reviews published from January 1, 2011 to December 31, 2025 were retrieved from Web of Science Core Collection and Scopus. Bibliometric analyses were performed via VOSviewer, CiteSpace and Scimago Graphica, including annual publication volume, collaboration networks of countries, institutions and authors, co-citation of journals and references, and keyword co-occurrence, clustering and bursting. ResultsA total of 917 literatures were included. The annual number of publications showed a sustained upward trend. The United States and the United Kingdom took the leading position in publication output and academic influence. The University of Toronto was the most productive institution, and Anne E. Holland was the most prolific author. European Respiratory Journal and American Journal of Respiratory and Critical Care Medicine were high-impact journals. COPD, pulmonary rehabilitation, telerehabilitation and telemedicine were high-frequency core keywords. Machine learning, interstitial lung disease, virtual reality and digital health were the bursting keywords in recent years. ConclusionThe researches on digital pulmonary rehabilitation for COPD are increasing continuously in the past 15 years. The research focus has shifted from hospital-based standardized rehabilitation to community home digital rehabilitation centered on patient self-management. Future studies will focus on the deep integration of multiple digital technologies and extension of rehabilitation protocols to other chronic respiratory diseases.

BACKGROUND:Post and core restoration is a common choice for tooth defects,but the repair effects of various post and core materials are different. OBJECTIVE:To evaluate the stress distribution at the post and core,tooth root,and bonding agent site of post and core models made of different elastic modulus post and core materials using finite element method. METHODS:A three-dimensional root canal treated maxillary central incisor model was built using three-dimensional modeling software,which was restored with a full ceramic crown.The post and core materials in the restoration used nanoceramic resin(elastic modulus=12.8 GPa),composite resin(elastic modulus=16 GPa),hybrid ceramic(elastic modulus=34.7 GPa),glass ceramic(elastic modulus=95 GPa),titanium alloy(elastic modulus=112 GPa),and zirconia(elastic modulus=209.3 GPa).The model was fixed in cortical bone.A 100 N concentrated force of 45° from the long axis of the tooth was applied to 1/3 of the crown and tongue side of the central incisor.The stress distribution of the post and core,dentin,and tooth-root bonding agent in the model was repaired by the maximum principal stress criterion. RESULTS AND CONCLUSION:(1)When the post and core materials with higher elastic modulus was used,the post-core stress in the repair model was more concentrated.When the elastic modulus of the post and core materials(nanoceramic resin and composite resin)was close to dentin,the stress distribution of the post and core was more uniform.The stress distribution of dentin in all restoration models was similar regardless of post and core materials.When the post and core with higher elastic modulus was used,more stress concentration was shown at the post and root bonding agent in the repair model.(2)The maximum stress values at the post and core,tooth root,and the bonding agent site of post and tooth root in the nanoceramic resin model were 31.00,33.21,and 0.51 MPa,respectively.The maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root in the composite resin model were 36.84,33.14,and 0.59 MPa,respectively.In the mixed ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 64.05,32.83,and 1.00 MPa,respectively.In the glass ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 112.30,32.69,and 1.73 MPa,respectively.In the titanium alloy model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 120.00,32.17,and 1.86 MPa,respectively.In the zirconia model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 148.80,31.85,and 2.28 MPa,respectively.(3)The higher the elastic modulus of the post and core material,the higher the maximum stress at the post and core during restoration.The elastic modulus of the post and core material had no significant effect on the maximum stress of the dental bonding agent and dentin.

Objective:To investigate the role and mechanism of leucine-rich α-2-glycoprotein 1 (LRG1) in the fibrosis of human pterygium fibroblasts (HPFs).Methods:A total of 30 nasal primary pterygium tissues from patients who underwent pterygium excision surgery and 30 nasal normal conjunctival tissues from patients who underwent strabismus correction surgery were collected from the First Affiliated Hospital of Harbin Medical University between January 2022 and March 2023, serving as the pterygium group and normal control group, respectively.LRG1 protein expression in both groups was detected by immunofluorescence staining.The mRNA and protein levels of LRG1 and transforming growth factor-β1 (TGF-β1) were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot.Primary HPFs were cultured from excised pterygium tissues using tissue block adhesion method, and cell morphology was observed.Vmentin and cytokeratin were identified by immunofluorescence staining.HPFs were divided into recombinant human LRG1 (rhLRG1) group and blank control group treated with or without 10 μg/ml rhLRG1 for 24 hours, respectively, and cell migration was evaluated via scratch assay.Additionally, HPFs were divided into blank control group, LRG1 overexpression group and LRG1 knockdown group.HPFs in LRG1 overexpression group and LRG1 knockdown group were transfected with LRG1 overexpression plasmids and small interfering RNA for 24 hours, respectively.TGF-β1 mRNA level was evaluated by qRT-PCR and expression of TGF-β1, fibronectin (FN), type Ⅲ collagen (COL3), and α-smooth muscle actin (α-SMA) proteins were evaluated by Western blot.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (No.2022IIT026).Written informed consent was obtained from each subject.Results:HPFs were successfully isolated, exhibiting spindle-shaped morphology with whorled arrangement, positive identification for vimentin, and negative immunofluorescence staining for cytokeratin.The migration rate of the rhLRG1 group was (83.01±2.56)%, significantly higher than (50.32±4.97)% of the blank control group ( t=9.59, P<0.001).Immunofluorescence staining results showed that compared with normal conjunctival tissue, LRG1 protein was significantly higher expressed in pterygium tissue and was widely distributed in fibrous connective tissue and epithelial layer.Both mRNA and protein levels of LRG1 and TGF-β1 were significantly higher in the pterygium group than in the normal control group (mRNA: t=10.18, 6.15, both P<0.05.protein: t=6.83, 8.79, both P<0.05).In the LRG1 overexpression group, mRNA level of TGF-β1, and protein levels of FN, COL3 and α-SMA were significantly increased compared with the blank control and LRG1 knockdown groups (all P<0.05). Conclusions:LRG1 promotes fibrosis and enhances the migration ability in HPFs, and its mechanism may be associated with the upregulation of the TGF-β1 signaling pathway.

Objective:To explore the characteristics of nutrition self-management of home-based elderly chronic obstructive pulmonary disease (COPD) patients based on user persona, in order to provide reference for accurate home nutrition management.Methods:From July to December 2023, home-based elderly COPD patients in the Department of Respiratory and Critical Care Medicine of General Hospital of Ningxia Medical University were selected by convenience sampling method. The Mini Nutritional Assessment, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Physical Activity Rating Scale-3, COPD Patients Self-Management Scale were used to conduct questionnaire survey. The SPSS 26.0 software was used to analyze the influencing factors of patients′ self-management of nutrition. Attributes with statistical significance ( P<0.05) were extracted as labels, and the visualization of patients′ self-management of nutrition portraits was completed in the form of pictures combined with labels. Results:A total of 320 questionnaires were distributed, and 309 valid questionnaires were collected. Among 309 home-based elderly COPD patients, there were 210 males and 99 females with an age of (69.14 ± 6.84) years old. According to the data analysis results, three dimensions of natural attributes, social attributes, and behavioral tracks were artificially extracted to construct three types of nutritional self-management user persona for home-based elderly COPD patients, respectively namely blind management type, independent attempt type, and powerless type.Conclusions:There are great differences in the nutritional status and self-management of home-based elderly patients with COPD. Accurate management measures can be developed based on user persona analysis to improve their nutritional status.

Objective:To study the application of Internet+ follow-up model based on nutrition support team (NST) cooperation in enteral nutrition therapy for patients with inflammatory bowel disease (IBD).Methods:From November 2021 to April 2023, 98 IBD patients admitted to the First Affiliated Hospital of Anhui Medical University were prospectively enrolled and were divided into the observation and control groups (49 cases in each group) using a random number table. The observation group received the intervention of Internet+ follow-up based on NST cooperation and the control group was given routine telephone follow-up. The nutritional indicators, IBD quality of life score, and patient satisfaction with care were compared between the two groups before and 3 months after the intervention.Results:After intervention, the serum albumin, hemoglobin, and pre-albumin levels in the observation group were significantly higher than those in the control group (all P<0.05). After intervention, the IBD quality of life scores of patients in the observation group were significantly higher than those in the control group, in the domains including daily activities, bowel function, social function, and emotional ability (all P<0.05). The patient satisfaction with care in the observation group was 93.62% (44/47), which was significantly higher than that (76.60%, 36/47) in the control group ( P<0.05). Conclusion:The Internet+ follow-up model based on NST cooperation favors the enteral nutrition therapy for patients with IBD as it improves the nutritional status, quality of life, and patient satisfaction with care.