Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

Objective: To assess the nutritional status of primary and secondary school students in Beijing City and to analyze the related factors, so as to provide a scientific basis for improving the nutritional status of primary and secondary school students in a targeted manner. Methods: Based on the 2021 Beijing Student Common Diseases and Health Influencing Factors Surveillance Project, a stratified random cluster sampling method was used to conduct a physical examination and questionnaire survey on 25 487 primary and secondary school students from September to November 2021. The Chi square test was used for comparison of nutritional status detection rates, and disordered multi classification Logistic regression analysis was used to explore the factors associated with students nutritional status. Results: The detection rates of malnutrition, overweight and obesity among primary and secondary school students in Beijing City were 4.7%, 18.0% and 23.8% respectively. The detection rates of malnutrition, overweight and obesity were higher among male students (5.1%, 20.4%, 29.7%) than female students (4.2%, 15.5%, 17.4%) ( χ 2= 12.23, 101.71, 526.99, P <0.01). The detection rate of obesity was higher in the suburbs than urban areas(26.6%, 19.8%), and the detection rate of malnutrition was lower in the suburbs than urban areas (4.2%,5.5%)( χ 2=157.25, 23.61, P <0.01). The results of disordered multi classification Logistic regression showed that the related factors for malnutrition, overweight and obesity were gender, residence, moderate to vigorous exercise ≥60 min per day and lack of sleep( OR =1.70, 1.88,2.48; 1.14, 0.87, 0.67; 0.85, 0.92, 0.81 ; 0.83, 1.08, 1.07); frequency of fried food intake daily was a related factor for overweight ( OR =0.70); whether eating breakfast daily or not was a related factor for overweight and obesity ( OR =0.91, 0.84); academic level (middle and high school) was a related factor for malnutrition and obesity ( OR =1.38, 1.37; 0.77, 1.40)( P <0.05). Conclusions The problem of overweight and obesity among primary and secondary school students in Beijing City continues to be serious, especially among boys and suburban areas. It is recommended that society, schools, families and individuals should work together to improve the nutritional status of primary and secondary school students by adopting a graded and classified approach.

OBJECTIVE: To investigate the clinical application of high-frequency color Doppler ultrasound (HFCDU) in detecting perforators in the deep adipose layers for harvesting super-thin anterolateral thigh flap (ALTF). METHODS: Between August 2019 and January 2023, 45 patients (46 sides) with skin and soft tissue defects in the foot and ankle were treated, including 29 males and 16 females, aged from 22 to 62 years, with an average of 46.7 years. The body mass index ranged from 19.6 to 36.2 kg/m ², with an average of 23.62 kg/m ². The causes of injury included traffic accident injury in 15 cases, heavy object crush injury in 20 cases, mechanical injury in 8 cases, heat crush injury in 1 case, and chronic infection in 1 case. There were 20 cases on the left side, 24 cases on the right side, and 1 case on both sides. After thorough debridement, the wound size ranged from 5 cm×4 cm to 17 cm×11 cm. All patients underwent free super-thin ALTF transplantation repair. HFCDU was used to detect the location of the perforators piercing the deep and superficial fascia, as well as the direction and branches of the perforators within the deep adipose layers before operation. According to the preoperative HFCDU findings, the dimensions of the super-thin ALTF ranged from 6 cm×4 cm to 18 cm×12 cm. The donor sites of the flaps were directly sutured. RESULTS: A total of 55 perforators were detected by HFCDU before operation, but 1 was not found during operation. During operation, a total of 56 perforators were found, and 2 perforators were not detected by HFCDU. The positive predictive value of HFCDU for identifying perforator vessels was 98.2%, and the sensitivity was 96.4%. Among the 54 perforators accurately located by HFCDU, the orientation of the perforators in the deep adipose layers was confirmed during operation. There were 21 perforators (38.9%) traveled laterally and inferiorly, 12 (22.2%) traveled medially and inferiorly, 14 (25.9%) traveled laterally and superiorly, 5 (9.3%) traveled medially and superiorly, and 2 (3.7%) ran almost vertically to the body surface. Among the 54 perforators accurately located by HFCDU, 35 were identified as type 1 perforators and 12 as type 2 perforators (HFCDU misidentified 7 type 2 perforators as type 1 perforators). The sensitivity of HFCDU in identifying type 1 perforators was 100%, with a positive predictive value of 83.3%. For type 2 perforators, the sensitivity was 63.2%, and the positive predictive value was 100%. The surgeries were successfully completed. The super-thin ALTF had a thickness ranging from 2 to 6 mm, with an average of 3.56 mm. All super-thin ALTF survived, however, 1 flap experienced a venous crisis at 1 day after operation, but it survived after emergency exploration and re-anastomosis of the veins; 1 flap developed venous crisis at 3 days after operation but survived after bleeding with several small incisions; 3 flaps had necrosis at the distal edge of the epidermis, which healed after undergoing dressing changes. All 45 patients were followed up 6-18 months (mean, 13.6 months). Three flaps required secondary defatting procedures, while the rest had the appropriate thickness, and the overall appearance was satisfactory. CONCLUSION Preoperative application of HFCDU to detect the perforator in the deep adipose layers can improve the success and safety of the procedure by facilitating the harvest of super-thin ALTF.
Male ; Female ; Humans ; Thigh/surgery* ; Plastic Surgery Procedures ; Prospective Studies ; Skin Transplantation ; Free Tissue Flaps ; Burns ; Soft Tissue Injuries/surgery* ; Ultrasonography, Doppler, Color ; Crush Injuries/surgery* ; Perforator Flap ; Treatment Outcome

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC₅₀ of 30.96 μmol·L^-1, and KBA (30 μmol·L^-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

BACKGROUND:Myelodysplastic syndrome has worse hazards of acute myeloid leukemia transformation,and some studies have revealed that immune infiltration plays a vital part in the two.Nevertheless,more studies are required to confirm the relationship between immune infiltration and related differentially expressed gene regulation. OBJECTIVE:To screen the differentially expressed genes with prognostic significance between myelodysplastic syndrome and acute myeloid leukemia by bioinformatics analysis and explore the possible roles and mechanisms among these differentially expressed genes and immune infiltration mechanisms in the occurrence and progression of diseases. METHODS:The differentially expressed genes were screened for bioinformatics analysis using the GEO datasets,and analyzed by DO,GO,KEGG and GSEA.The TCGA prognostic database was used to plot the K-M curves of differentially expressed genes and receiver operating characteristic curve analysis was applied to evaluate the clinical diagnostic performance.Finally,CIBERSORT analysis was used to intuitively demonstrate the correlation between critical prognostic genes and the distribution of immuno-infiltrated cells.RT-qPCR was employed to detect peripheral blood samples from healthy controls,myelodysplastic syndrome and acute myeloid leukemia patients so as to verify the crucial genes preliminarily. RESULTS AND CONCLUSION:(1)A total of 150 differentially expressed genes were obtained between myelodysplastic syndrome and acute myeloid leukemia,among which 16 genes were up-regulated and 134 were down-regulated.(2)The results of DO,GO,KEGG and GSEA analysis suggested that differentially expressed genes might promote the development of myelodysplastic syndrome to acute myeloid leukemia by regulating the immune response.CIBERSORT revealed the differences in immune infiltration between myelodysplastic syndrome and acute myeloid leukemia.The distribution of CD4+ T cells,monocytes,neutrophils and M1 macrophages decreased in acute myeloid leukemia patients.In contrast,the distribution of inflammatory suppressor cells M2 macrophages increased,suggesting that it may be related to the immunosuppression of acute myeloid leukemia.(3)K-M curve and receiver operating characteristic curve analysis of 150 differentially expressed genes screened out four genes relevant to immunity and prognosis with good diagnostic performance:MANSC1,FLT3,BMX and CXCR2.(4)The results of RT-qPCR exhibited that MANSC1,BMX and CXCR2 were low expressed,while FLT3 was highly expressed in acute myeloid leukemia patients.These findings verify that the differential expression of MANSC1,FLT3,BMX and CXCR2 in patients with myelodysplastic syndrome and acute myeloid leukemia is not only significantly correlated with the prognosis of patients but may also affect the occurrence and development of myelodysplastic syndrome and acute myeloid leukemia by regulating the immune infiltration of patients.They can be used as potential biomarkers and therapeutic targets of the transformation from myelodysplastic syndrome to acute myeloid leukemia,providing a new direction for clinical diagnosis and treatment of the transformation of myelodysplastic syndrome.

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

ObjectiveRecent successful restoration of the native conformation and function of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs) demonstrates that the era of molecular conformational engineering is dawning. Basically, molecular conformational engineering aims to precisely tune flexible non-functional molecules into special conformations to carry out novel functions, in the same way as protein folding. In order to explore the general applicability of molecular conformational engineering, as well as to reveal the mechanism of protein structure-function relationship, the objective of this work is to restore the native conformation and function of the CDRs of an antibody on platinum nanoparticles (PtNPs). MethodsThe CDR fragment of the anti-lysozyme antibody cAB-lys3, which has no stable conformation or function in free state, was conjugated onto the surface of PtNPs through two Pt-S bonds. The original antigen-recognizing function of the CDR restored on PtNPs was assessed by the specific inhibition of the enzymatic activity of lysozyme by the PtNP-CDR conjugates. ResultsAfter optimization of the peptide density on the surface of PtNPs and modification of PtNPs with polyethylene glycol (PEG), the resulted PtNP-based hybrid artificial antibody (PtNP-10PEG-30P1), dubbed Platinumbody, could bind specifically to lysozyme and significantly inhibit the activity of lysozyme. ConclusionThis is the first time that the fragment of a protein could refold on PtNPs. Together with the previous Goldbody and Silverbody, current work demonstrates that artificial proteins could be generally created by restoration of the native conformation of natural proteins fragments on NPs.