The repair of bone defects is heavily influenced by the dynamic osteogenic microenvironment. Static scaffolds constructed by traditional 3D printing technology cannot simulate the dynamic nature of the microenvironment during bone defect repair due to the fixed structure, uncontrollable release of active factors, and difficult regeneration of blood vessels, among other factors. Breaking through the limitations of these static scaffolds and realizing the intelligent and dynamic regulation of the osteogenic microenvironment is a key scientific issue in the field of bone tissue engineering. 4D printing technology combines the dynamic responsiveness of bone restoration materials with the concept of intelligent design to regulate the micro and macro structure of scaffolds. This technology provides a new method for bone tissue engineering by responding to endogenous and exogenous stimuli and creating a better osteogenic microenvironment through functionalized design, including drug delivery and antibacterial function. However, this technology currently suffers from challenges related to dynamic response material design, insufficient precision of printing technology, and mismatches between multi-stimulus response systems, metabolic rhythms of bone tissue, and functionalized composite scaffolds. Future research should focus on the development of smart response materials with excellent dynamic responses and bioactivity, the creation of new printing technologies, and the design of personalized and precise bone repair solutions. The aim of this paper is to review the current research status of 4D printing for bone tissue engineering in terms of material types, response mechanisms, and applications to provide a theoretical basis for the development and clinical application of functional bone repair materials in the future.

Depression is a common mental disorder that falls under the category of "stagnation syndrome" in traditional Chinese medicine （TCM）. Its complex pathogenesis poses challenges for the development of novel therapeutic agents. Currently， clinically used antidepressants are often accompanied by significant side effects， and statistics show that about one-third of patients do not respond to these medications. TCM demonstrates advantages in the treatment of depression through multi-target， multi-pathway and multi-mechanistic approaches. Pinelliae Rhizoma， a phlegm-resolving herb， exhibits effects such as drying dampness and resolving phlegm， as well as eliminating stuffiness and reducing masses. The characteristics of harmonizing Yin and Yang and resolving stagnation in the middle energizer align precisely with the pathogenesis of depression syndrome， demonstrating therapeutic efficacy in affected patients. Literature studies have found that the active ingredients of Pinelliae Rhizoma， such as cavidine， baicalein， β-sitosterol， as well as Pinelliae Rhizoma herb pairs， such as Pinelliae Rhizoma-Magnoliae Officinalis Cortex， Pinelliae Rhizoma-husked sorghum， Pinelliae Rhizoma-Prunellae Spica， exhibit significant antidepressant effects. Furthermore， TCM formulas containing Pinelliae Rhizoma as the principal therapeutic agent， such as Banxia Xiexin Tang， Banxia Houpo Tang， and Wendan Tang， as well as formulas incorporating Pinelliae Rhizoma like compound Xiaochaihu Tang， Chaihu Jia Longgu Muli Tang， and Erchen Tang， have also demonstrated favorable antidepressant efficacy. The antidepressant mechanism of these agents may involve modulation of 5-hydroxytryptamine （5-HT） and dopamine （DA） levels， up-regulation of brain-derived neurotrophic factor （BDNF） expression， regulation of the hypothalamus-pituitary-adrenal （HPA） axis， reduction of oxidative stress， modulation of nuclear transcription factor-κB （NF-κB） signaling pathway， and inhibition of microglia-mediated inflammatory responses. This review summarized the antidepressant mechanisms and clinical applications of the active components， herb pairs， and TCM formulas containing Pinelliae Rhizoma， aiming to provide a reference for modern research on the use of Pinelliae Rhizoma in antidepressant therapy.

ObjectiveTo develop a full-process data platform of renal rehabilitation, diagnosis and quality control information. MethodsA hierarchical architectural design was proposed, adhering to clinical pathway models and standardized data protocols. The platform comprehensively covered assessment, intervention, follow-up and quality control for maintenance hemodialysis (MHD) patients. By integrating multidisciplinary resources and standardizing rehabilitation workflows, it delivered standardized and intelligent rehabilitation services. ResultsThe platform achieved standardized and intelligent management of rehabilitation services, effectively improved the physiological function, psychological state and quality of life convenience for MHD patients, while significantly reduced the economic and care burden on patients' families and society. ConclusionThe rehabilitation service model based on a full-process data platform may provide scientific and systematic support for MHD patients.

Objective To investigate the weight loss efficacy and mechanisms of oligopeptide-herbal medicine composite,and to provide new approaches for obesity treatment.Methods Twenty-three SPF female SD rats were randomly divided into control group(n=3)and modeling group(n=20).The control group was fed an ordinary diet for 6 consecutive weeks,and the modeling group was fed a high-fat diet for 6 consecutive weeks to establish a simple obesity rat model.After successful modeling,the modeling group was randomly divided into model group(n=10)and treatment group(n=10).The treatment group started anoint-and-massage therapy with oligopeptide-herbal medicine composite(3 g per rat per time,once a day,20 min each time),which was recorded as day 1.The control group and model group were not treated with oligopeptide-herbal medicine composite but received the same massage,and continued to be fed ordinary feed and high-fat feed respectively.Ten rats in the model group and ten in the treatment group were each divided into 3 groups,with 3,3,and 4 rats in each group.On days 3,6,and 9 after treatment,the rats in the three groups were weighed and cardiac blood collection was performed after isoflurane respiratory anesthesia.After euthanasia by cardiac bloodletting,abdominal subcutaneous adipose tissue(aSAT)and perirenal white adipose tissue(pWAT)samples were collected and weighed.Serum triglycerides(TG)and high-density lipoprotein cholesterol(HDL-C)levels were measured.Image J software was used to measure aSAT thickness and the diameter and area of perirenal white adipocytes and abdominal subcutaneous adipocytes.Immunofluorescence technique was used to observe the number of telocytes(TCs),cell junctions and exosomes per unit area of aSAT.Transmission electron microscopy was used to measure the length of telopodes(Tps)of dermal and subcutaneous TCs in abdominal skin,and to observe the distribution of exosome vesicles,rough endoplasmic reticulum,mitochondria,and cell junctions.Results Compared with the control group,the body weight of rats in the modeling group increased significantly(P＜0.05).Compared with the control group,rats in the model group showed a significant increase in serum TG level,a significant decrease in HDL-C level,and a significant increase in pWAT mass(all P＜0.05).Compared with the model group,the treatment group showed a significantly increased rate of body weight reduction,significantly decreased pWAT mass,significantly decreased serum TG level,and significantly increased HDL-C level(all P＜0.05).Compared with the model group,the treatment group showed significant reductions in aSAT thickness,as well as cell diameter and area in both aSAT and pWAT(all P＜0.05).Compared with the model group,the treatment group showed significantly increased number of TCs per unit area of aSAT,number of exosomes from TCs in aSAT,and Tps length(all P＜0.05).The treatment group showed an increasing trend in the numbers of mitochondria,rough endoplasmic reticulum,and cell junctions in TCs.Conclusion Oligopeptide-herbal medicine composite applied via anoint-and-massage therapy effectively improves obesity-related symptoms such as dyslipidemia and fat accumulation in obese rats by regulating TCs and their intercellular communication.

Japanese encephalitis virus(JEV)usually evades the inhibitory effect of the innate immunity factor type Ⅰ interferon(Ⅰ-IFN)when it infects human cells and tissues.The virus then causes a series of serious symptoms,such as spasticity,neurodegenerative lesions,neuroinflammation,and even death.Generally,JEV escapes innate immunity by inhibiting IFN-α/β production and the interferon Janus kinase-signal transducer and activator of transcription signaling pathway.Because of this special immune escape mechanism,various mouse infection models have been constructed for the study of the pathogenesis of and therapeutic regimens for JEV infections.In this review,based on an exposition of the IFN immune escape mechanism of JEV,we systematically introduce the concept of JEV-infected mouse models and analyze the characteristics of these models and the degree to which they simulate human symptoms.The intention is to develop various new JEV-infected mouse models based on potential new research targets and provide novel ideas for animal models for JEV research.

Purpose To investigate the role of 18F-FDG PET/CT in predicting histological grade of invasive pulmonary adenocarcinoma in the WHO(2021)classification.Materials and Methods The Clinical,pathological and PET/CT data of 255 patients with invasive pulmonary adenocarcinoma confirmed by surgical pathology were retrospectively analyzed from May 2015 to August 2023.Tertiary tumor grading was performed according to the WHO(2021)classification.The clinicopathologic features,maximum standardized uptake value(SUVmax),maximum standardized uptake,total lesion glycolysis and CT imaging findings were compared among the three tumor grades.Logistic regression analysis was used to screen the independent predictors for grade 3 tumors,and performance evaluation was performed using receiver operating characteristic curve.Results Higher tumor grade was associated with male sex(χ2=11.803,P=0.003),smoking history(χ2=7.702,P=0.021),maximum tumor diameter(H=20.548,P=0.002),lymph node metastasis(P<0.001),vascular cancer thrombus(χ2=33.270,P<0.001),pleural invasion(χ2=15.116,P=0.001)and airway spread(χ2=17.867,P<0.001).SUVmax(H=71.488,P<0.001),total lesion glycolysis(H=30.658,P<0.001)and the proportion of pure solid tumors on CT image(χ2=28.872,P<0.001)all increased significantly with higher tumor grade.A higher SUVmax(OR=1.234,95%CI 1.141-1.334,P<0.001)and pure solid appearance(OR=2.205,95%CI 1.166-4.171,P=0.015)were independent predictors of grade 3 tumors.The area under the receiver operating characteristic curve for SUVmax,CT solid appearance and the combination for predicting grade 3 tumors was 0.793,0.641 and 0.804,respectively,with the SUVmax cut-off of 6.08.Conclusion SUVmax and CT solid appearance are independent predictive factors for grade 3 invasive pulmonary adenocarcinoma.Preoperative 18F-FDG PET/CT can assist in evaluating the grading of invasive pulmonary adenocarcinoma,which improves treatment decision-making.

Objective To investigate the weight loss efficacy and mechanisms of oligopeptide-herbal medicine composite,and to provide new approaches for obesity treatment.Methods Twenty-three SPF female SD rats were randomly divided into control group(n=3)and modeling group(n=20).The control group was fed an ordinary diet for 6 consecutive weeks,and the modeling group was fed a high-fat diet for 6 consecutive weeks to establish a simple obesity rat model.After successful modeling,the modeling group was randomly divided into model group(n=10)and treatment group(n=10).The treatment group started anoint-and-massage therapy with oligopeptide-herbal medicine composite(3 g per rat per time,once a day,20 min each time),which was recorded as day 1.The control group and model group were not treated with oligopeptide-herbal medicine composite but received the same massage,and continued to be fed ordinary feed and high-fat feed respectively.Ten rats in the model group and ten in the treatment group were each divided into 3 groups,with 3,3,and 4 rats in each group.On days 3,6,and 9 after treatment,the rats in the three groups were weighed and cardiac blood collection was performed after isoflurane respiratory anesthesia.After euthanasia by cardiac bloodletting,abdominal subcutaneous adipose tissue(aSAT)and perirenal white adipose tissue(pWAT)samples were collected and weighed.Serum triglycerides(TG)and high-density lipoprotein cholesterol(HDL-C)levels were measured.Image J software was used to measure aSAT thickness and the diameter and area of perirenal white adipocytes and abdominal subcutaneous adipocytes.Immunofluorescence technique was used to observe the number of telocytes(TCs),cell junctions and exosomes per unit area of aSAT.Transmission electron microscopy was used to measure the length of telopodes(Tps)of dermal and subcutaneous TCs in abdominal skin,and to observe the distribution of exosome vesicles,rough endoplasmic reticulum,mitochondria,and cell junctions.Results Compared with the control group,the body weight of rats in the modeling group increased significantly(P＜0.05).Compared with the control group,rats in the model group showed a significant increase in serum TG level,a significant decrease in HDL-C level,and a significant increase in pWAT mass(all P＜0.05).Compared with the model group,the treatment group showed a significantly increased rate of body weight reduction,significantly decreased pWAT mass,significantly decreased serum TG level,and significantly increased HDL-C level(all P＜0.05).Compared with the model group,the treatment group showed significant reductions in aSAT thickness,as well as cell diameter and area in both aSAT and pWAT(all P＜0.05).Compared with the model group,the treatment group showed significantly increased number of TCs per unit area of aSAT,number of exosomes from TCs in aSAT,and Tps length(all P＜0.05).The treatment group showed an increasing trend in the numbers of mitochondria,rough endoplasmic reticulum,and cell junctions in TCs.Conclusion Oligopeptide-herbal medicine composite applied via anoint-and-massage therapy effectively improves obesity-related symptoms such as dyslipidemia and fat accumulation in obese rats by regulating TCs and their intercellular communication.

ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees， so as to elucidate the scientific connotation of "only those that grow on stones has superior quality"， and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis（PCA）， hierarchical cluster analysis（HCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection（VIP） value≥1 and log₂fold change（FC）≥1 or ≤-1， and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes， dominated by flavonoids（292）， phenolic acids（284）， and alkaloids（189）. Through OPLS-DA screening， 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile， epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids， phenolic acids， alkaloids， lignans and coumarins， while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids， and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis， flavonoid biosynthesis， tyrosine metabolism， and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids， flavonoids， and alkaloids in D. nobile， indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis， and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.