ObjectiveTo observe the clinical effect of modified Huanglian Wendantang on cardiovascular risk factors in patients with metabolic syndrome under the guidance of treating disease before its onset. MethodsA total of 82 patients with metabolic syndrome treated in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2023 to July 2024 were selected and allocated into an observation group （41 cases） and a control group （41 cases） by the random number table method. The control group received routine treatment， and the observation group was treated with modified Huanglian Wendantang on the basis of routine treatment. Both groups were treated for 8 weeks. The therapeutic effects on TCM symptoms after treatment in the two groups were evaluated. The levels of obesity degree indicators， blood pressure indicators， glucose and lipid metabolism indicators， inflammatory factors， and vascular endothelial function indicators before and after treatment in the two groups were measured， and the treatment safety was evaluated. ResultsAfter treatment， the total response rate of TCM symptoms in the observation group was 97.56% （40/41）， which was higher than that （87.80%， 36/41） in the control group （χ²=5.205， P<0.05）. After treatment， both groups showed declines （P<0.05） in systolic blood pressure （SBD）， diastolic blood pressure （DBP）， triglyceride （TG）， total cholesterol （TC）， low density lipoprotein cholesterol （LDL-C）， fasting blood glucose， 2-hour postprandial blood glucose （2 h PG）， glycosylated hemoglobin （HbA1c）， fasting insulin （FINS）， Homeostatic Model Assessment for Insulin Resistance （HOMA-IR）， body mass index （BMI）， waist circumference （WC）， waist-to-hip ratio （WHR）， leptin （LEP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， endothelin-1 （ET-1）， and inducible nitric oxide synthase （iNOS）. Moreover， the declines in the observation group were more obvious than those in the control group （P<0.05， P<0.01）. After treatment， both groups showed elevated levels of high density lipoprotein cholesterol （HDL-C）， adiponectin （ADP）， nitric oxide （NO）， and endothelial nitric oxide synthase （eNOS） （P<0.05）， and the above indexes in the observation group were higher than those in the control group （P<0.01）. ConclusionUnder the guidance of the thought of treating disease before its onset， modified Huanglian Wendantang was used to treat patients with metabolic syndrome. The decoction improved the clinical efficacy by ameliorating IR to improve insulin sensitivity， reducing inflammation， and protecting the vascular endothelial function. It inhibits cardiovascular risk factors without inducing adverse reactions， being worthy of clinical application and promotion.

OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

OBJECTIVE To study the improvement effects and mechanism of proanthocyanidins （PACs） on steroid-induced osteonecrosis of the femoral head （SONFH） in rabbits based on the receptor-interacting protein kinase 1 （RIPK1）/RIPK3/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS SONFH model in rabbits was induced by injecting Escherichia coli endotoxin+methylprednisolone. The successfully modeled rabbits were randomly divided into Model group （normal saline）， low-dose PACs group （PACs-L group， 11 mg/kg）， high-dose PACs group （PACs-H group， 22 mg/kg）， high-dose PACs+ RIPK1 activator （rRIPK1） group （PACs-H+rRIPK1 group， 22 mg/kg PACs+4 μg/kg rRIPK1）， along with a control group （normal saline）， with 6 rabbits in each group. Each administration group was given relevant medicine once a day intragastrically/via injection， for 4 consecutive weeks. After the last administration， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rabbit serum were measured. The changes in the microstructure of rabbit femurs， including bone mineral density （BMD）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular separation （Tb. Sp） were examined. The histopathological features of rabbit femoral tissues were observed， and the apoptotic status of cells within the rabbit femoral tissues was detected. The mRNA expressions of vascular endothelial growth factor （VEGF） and bone morphogenetic protein 2 （BMP2） in rabbit femoral tissues were determined. The expressions of RIPK1/RIPK3/MLKL signaling pathway-related proteins in femoral tissues were detected. RESULTS Compared with the Control group， serum contents of TNF-α and IL-6， Tb.Sp， empty bone cavity rate， cell apoptosis rate， phosphorylation levels of RIPK1， RIPK3 and MLKL in femoral tissue were significantly increased in the Model group （P＜0.05）. BMD， Tb.Th， Tb.N， as well as the mRNA expression of VEGF and BMP2， along with protein expression of caspase-8， in the femoral tissues were all decreased （P＜0.05）. The bone cells in the femoral tissue were unevenly distributed， and the trabeculae were arranged sparsely. Compared with the Model group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in all dosage groups of PACs showed significant improvements. Compared with the PACs-H group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in the PACs-H+rRIPK1 group showed significant reversal. CONCLUSIONS PACs can ameliorate SONFH in rabbits， and its mechanism of action may be related to the inhibition of the activation of the RIPK1/RIPK3/MLKL signaling pathway， suppression of apoptosis in femoral tissue cells， and promotion of angiogenesis.

OBJECTIVE: To investigate the expression and possible regulatory mechanism of miR-34a in the lung tissue of neonatal rat model of bronchopulmonary dysplasia (BPD) induced by hyperoxia. METHODS: In the study, 80 newborn SD rats were randomly divided into hyperoxia group (FiO₂=60%) and air group (FiO₂=21%) within 2 hours after birth, 40 rats per group. Lung tissue samples of the SD rats in each group were extracted on the 1st, 7th, 14th and 21st days after birth, and the pathological changes of lung tissue were observed under light microscope after HE staining. The number of radial alveolar counts (RAC) and the mean alveolar diameter (MAD) and the thickness of alveolar septal thickness (AST) were measured to evaluate the development of alveoli. Real-time fluorescence quantitative PCR was used to detect the expression of miR-34a, angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) in lung tissue of rats in hyperoxia group and air group at different time points. Enzyme-linked immunosorbent assay (ELISA) was used to detect the proteins expression of Ang-1 and Tie-2 in the lung tissues of the two groups at different time points. RESULTS: The weight of rats in the hyperoxia group on the 7th, 14th and 21st days after birth was significantly lower than that in the air group (P all < 0.05). With the prolongation of oxygen exposure, the number of alveoli decreased, the volume increased, the structure simplified, the alveolar cavity enlarged obviously and the alveolar septum thickened in the hyperoxia group. On the 7th, 14th and 21st days after birth, the RAC in the hyperoxia group was significantly lower than that in the air group (P all < 0.05). Compared with the air group, MAD and AST increased significantly on the 7th, 14th and 21st days after birth in the hyperoxia group, and the difference was statistically significant (P all < 0.05). The expression level of miR-34a in lung tissue of hyperoxia group was significantly higher than that of air group on the 7th, 14th and 21st days after birth, and the difference was statistically significant (P all < 0.05). Compared with the air group at the same time point, the expression levels of Ang-1 and Tie-2 mRNA and protein in the hyperoxia group were lower than those in the air group on the 14th and 21st days after birth (P all < 0.05). CONCLUSION The new BPD model of newborn SD rats can be successfully established by continuous exposure to 60% hyperoxia. The expression of miR-34a was up-regulated in the lung tissue of the new BPD model of neonatal rats. MiR-34a may play an important role in the occurrence and development of BPD by regulating Ang-1/Tie-2 signal pathway.
Animals ; MicroRNAs/metabolism* ; Bronchopulmonary Dysplasia/genetics* ; Hyperoxia/metabolism* ; Rats, Sprague-Dawley ; Animals, Newborn ; Rats ; Angiopoietin-1/genetics* ; Disease Models, Animal ; Receptor, TIE-2/genetics* ; Lung/pathology* ; Male

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Microalgae possess high photosynthetic efficiency, robust adaptability, and substantial biomass, serving as excellent biological resources for large-scale cultivation. Malic enzyme (ME), a ubiquitous metabolic enzyme in living organisms, catalyzes the decarboxylation of malate to produce pyruvate, CO₂, and NAD(P)H, playing a role in multiple metabolic pathways including energy metabolism, photosynthesis, respiration, and biosynthesis. In this study, we identified the Scenedesmus quadricauda malic enzyme gene (SqME) and its biological functions, aiming to provide excellent target genes for the genetic improvement of higher plants. Based on the RNA-seq data from S. quadricauda under the biofilm cultivation mode with high CO₂ and light energy transfer efficiency and small water use, a highly expressed gene (SqME) functionally annotated as ME was cloned. The physicochemical properties of the SqME-encoded protein were systematically analyzed by bioinformatics tools. The subcellular localization of SqME was determined via transient transformation in Nicotiana benthamiana leaves. The biological functions of SqME were identified via genetic transformation in Nicotiana tabacum, and the potential of SqME in the genetic improvement of higher plants was evaluated. The ORF of SqME was 1 770 bp, encoding 590 amino acid residues, and the encoded protein was located in chloroplasts. SqME was a NADP-ME, with the typical structural characteristics of ME. The ME activity in the transgenic N. tabacum plant was 1.8 folds of that in the wild-type control. Heterologous expression of SqME increased the content of chlorophyll a, chlorophyll b, and total chlorophyll by 20.9%, 26.9%, and 25.2%, respectively, compared with the control. The transgenic tobacco leaves showed an increase of 54.0% in the fluorescence parameter NPQ and a decrease of 30.1% in Fo compared with the control. Moreover, the biomass, total lipids, and soluble sugars in the transgenic tobacco leaves enhanced by 20.5%, 25.7%, and 9.5%, respectively. On the contrary, the starch and protein content in the transgenic tobacco leaves decreased by 22.4% and 12.2%, respectively. Collectively, the SqME-encoded protein exhibited a strong enzymatic activity. Heterologous expressing of SqME could significantly enhance photosynthetic protection, photosynthesis, and biomass accumulation in the host. Additionally, SqME can facilitate carbon metabolism remodeling in the host, driving more carbon flux towards lipid synthesis. Therefore, SqME can be applied in the genetic improvement of higher plants for enhancing photosynthetic carbon fixation and lipid accumulation. These findings provide scientific references for mining of functional genes from S. quadricauda and application of these genes in the genetic engineering of higher plants.
Nicotiana/genetics* ; Photosynthesis/physiology* ; Malate Dehydrogenase/biosynthesis* ; Plant Leaves/genetics* ; Scenedesmus/enzymology* ; Carbon Cycle/genetics* ; Lipid Metabolism/genetics* ; Plants, Genetically Modified/metabolism*

Objective To explore the application effect of enteral nutrition-related diarrhea in postoperative esophageal cancer patients.Methods Based on literature search and expert meeting,a management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients was constructed.A convenience sampling method was used to select a total of 68 patients with enteral nutrition-related diarrhea after esophageal cancer surgery admitted to the thoracic surgery department of a tertiary A cancer hospital in Jiangsu Province.Among them,patients admitted from January 2022 to December 2022 were set as an experimental group.The experimental group was implemented the management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients.Those admitted from January 2021 to December 2021 were set as a control group with routine nursing.Then,the time of stopping diarrhea,the King's of Stool Chart(KSC-Tr)diarrhea score,and abnormal incidence of nutrition-related indexes,electrolytes abnormalities(low sodium,low potassium,and low calcium)were compared between 2 groups.Results The time of stopping diarrhea,KSC diarrhea score after 3 days of intervention and the time to achieve target feeding volume of the experimental group were lower than those in the control group,and the difference was statistically significant(P＜0.05).There were no significant differences in hemoglobin,albumin,prealbumin after 3 days of intervention,the incidence of electrolyte abnormalities(low sodium,low potassium,and low calcium)after 3 days of intervention,and the BMI index after 7 days of intervention between 2 groups(P＞0.05).Conclusion The management process for enteral nutrition-associated diarrhea in postoperative esophageal cancer patients can reduce the time of diarrhea,improve the severity of diarrhea,and shorten the time to achieve the target feeding,but has no significant change in the incidence of electrolyte abnormalities.

The incidence of myopia is increasing year by year and the trend of younger age is obvious. The situation of myopia prevention and control is very serious. The sclera is the target organ for the development of myopia. When myopia occurs and develops, the ultrastructure of the sclera tissue will undergo pathological changes, resulting in a decrease in its tensile strength, then progressive axial growth and posterior sclera expansion. Scleral collagen cross-linking can effectively increase the hardness and tensile strength of scleral tissue, which may have great potential in the prevention and control of myopia, especially pathological myopia. At present, the effectiveness of scleral collagen cross-linking technology in the prevention and treatment of pathological myopia researches are still in the stage of animal experiments, and there are a lot of controversies on the safety. The development of any new technology to ensure safety is the primary condition. A comprehensive understanding of the safety of scleral collagen crosslinking in the prevention and control of myopia can provide more basis and guidance for the further study of scleral collagen crosslinking.

ObjectiveWe conducted a drug resistance and homology analysis of diarrheagenic Escherichia coli （DEC） in Fengxian District of Shanghai in order to provide a basis for clinical rational drug use， risk monitoring and early warning. MethodsDEC were isolated from diarrheal patients in Fengxian District， Shanghai from 2019 to 2022. The minimum inhibitory concentrations （MIC） of 21 drugs to the DEC were determined. Genotyping and homology analysis were conducted with pulsed-field gel electrophoresis （PFGE）. ResultsThe DEC detection rate of diarrhea cases was 18.99% （131/690）， including enteroaggregative E.coli （EAEC） 64.89% （85/131）， enterotoxigenic E.coli （ETEC） 22.14% （29/131）， enteropathogenic E.coli （EPEC） 12.21% （16/131）， and enterohemorrhagic E.coli （EHEC） 0.76%（1/131）. The DEC detection showed obvious seasonal characteristics with a high incidence in summer. The DEC multidrug resistance rate was 66.41% with a total of 65 drug resistance profiles. The five antimicrobial drugs with the highest resistance rate were ampicillin （60.31%）， nalidixic acid （51.91%）， cefazolin （50.38%）， tetracycline （44.27%）， and cotrimoxazole （35.11%）. The rate of DEC resistance to levofloxacin was significantly increased from 2019 to 2022. Cluster analysis showed that the similarity of 85 EAEC cluster was 58.4%‒100.0%， and 69 band patterns were obtained. The similarity of 29 ETEC cluster was 58.5%‒100.0%， and 13 band patterns were obtained， including 2 dominant band types. The similarity of 16 EAEC clusters was 53.9%‒100.0%， and 15 band patterns were obtained. Five groups of homologous strains were found， consistent with the resistance phenotypes. ConclusionAmong the diarrhea cases， the DEC epidemic intensity is high， the drug resistance situation is severe， and the risk of outbreak infection is high in Fengxian District， Shanghai. Therefore， health monitoring and prevention need to be strengthened.

Due to the complexity of traditional Chinese medicine （TCM） interventions and the diversity of herbal components， single-omics technologies such as genomics， transcriptomics， proteomics， and metabolomics often cannot comprehensively elucidate the scientific connotations of TCM. Multi-omics technologies driven by system biology can analyze the theoretical connotations and application mechanisms of TCM from different levels such as genes， gene expression， proteins， and metabolites， in line with the holistic view of TCM， which helps to promote the modernization of TCM. By reviewing the literature on the application of omics technologies in the field of TCM， it is found that multi-omics technologies have been widely used in TCM for syndrome differentiation， evaluation of herbal quality， elucidation of pharmacological mechanisms， and drug toxicity assessment， providing comprehensive explanations of the mechanisms of action of TCM and overcoming the limitations of single-omics technologies， and having obtained significant achievements. However， multi-omics technologies also face challenges such as high cost， difficulties in data analysis due to large data volumes， and insufficient translation of research results. In the future， it is expected that through strengthening interdisciplinary cooperation， conducting long-term and dynamic clinical research， standardizing and normalizing data analysis processes， adopting appropriate and reasonable multi-omics integration patterns， establishing multi-omics databases for TCM， revealing the individualized characteristics， therapeutic mechanisms， and disease regulatory networks of TCM， the modernization of TCM will be promoted.