POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Currently, researchers have identified several mutated genes associated with hereditary eye diseases; however, effective therapeutic options remain scarce. The emergence of clustered regularly interspaced short palindromic repeats(CRISPR)and its associated proteins(CRISPR-associated proteins, Cas)offers a promising approach for treating these diseases. CRISPR/Cas9 enables precise targeting and modification of specific genetic sequences, allowing for the correction of mutated genes, as well as knockout or replacement of pathogenic genes to achieve therapeutic effects. In ophthalmology, CRISPR/Cas9 has been applied to various hereditary eye disorders, including corneal dystrophy, congenital cataracts, glaucoma, and retinitis pigmentosa. Additionally, significant progress has been made to utilize CRISPR/Cas9 to develop disease models. Therefore, it has great potential for clinical applications. However, challenges such as delivery efficiency and off-target effects remain. This review summarizes the mechanism of CRISPR/Cas9, its applications in genetic eye diseases and disease models, as well as the existing challenges, aiming to provide new insights for treatment.

ObjectiveTo investigate the effect of video-based educational intervention combined with maternal presence on perioperative adverse outcomes in preschool children undergoing general anesthesia， including cooperation in anesthesia induction， perioperative anxiety， pain and agitation during recovery. MethodsA total of 300 preschool children scheduled for general anesthesia in our hospital from June to December 2023 were randomly assigned to control group （n=150） and intervention group （n=150）. The control group received routine recovery care. For the intervention group， in addition to routine recovery care， a preoperative visit was scheduled one day before surgery. During this visit， mothers were guided to watch anesthesia videos with their children. During the waiting period in the operating room and 30 minutes after awakening， the mothers were guided to accompany the children for more than 30 minutes. Recovery conditions were recorded using the surgical anesthesia information system， and the children’s anesthetic induction compliance， perioperative anxiety， pain， and agitation were evaluated and recorded using the modified Yale Preoperative Anxiety Scale （m-YPAS）， the Induction Compliance Scale （ICC）， the Children’s Pain Behavior Scale （FLACC）， and the Pediatric Agitation and Emergence Delirium Scale （PAED）. ResultsOn the preoperative visit day， there were no statistically significant differences in baseline data between the two groups （P > 0.05）. For perioperative anxiety， the m-YPAS scores of the intervention group were significantly lower than those of the control group， both when entering the operating room waiting area （35.27±6.48 vs. 41.79±6.68， P < 0.05） and 30 minutes after postoperative recovery （20.13±7.05 vs. 35.75±9.51， P < 0.05）. In terms of anesthesia induction cooperation， the ICC scores of the intervention group were significantly lower than those of the control group （1.84±0.95 vs. 3.17±0.62， P < 0.05）， and the proportion of good induction cooperation was significantly higher than that of the control group （24.00% vs. 12.67%， P < 0.05）. There was no significant difference in awakening duration between the two groups， but the intervention group had a significantly shorter length of stay in the post-anesthesia care unit than the control group （0.90±0.29 hours vs. 1.29±0.42 hours， P < 0.001）. For perioperative agitation， the PAED scores of the intervention group were significantly lower than those of the control group （entering in the operating room waiting area： 8.5 vs. 9.2， P < 0.05； 30 minutes after postoperative recovery： 4.2 vs. 7.8， P < 0.05）. In terms of pain scores， the FLACC scores of the intervention group were also significantly lower than those of the control group， both when entering the operating room waiting area （ 5.3 vs. 6.7， P < 0.05； 30 minutes after postoperative recovery： 2.1 vs. 4.9， P < 0.05）. ConclusionsVideo-based educational intervention combined with maternal presence reduces the perioperative anxiety， pain and agitation of preschool children undergoing general anesthesia， and improved the compliance of anesthesia induction. It is recommended to promote this intervention measure in clinical practice.

OBJECTIVE: To review the research progress and challenges of poly (L-lactic acid) (PLLA) membrane in preventing tendon adhesion. METHODS: The relevant literature at home and abroad in recent years was extensively searched, covering the mechanism of tendon adhesion formation, the adaptation challenge and balancing strategy of PLLA, the physicochemical modification of PLLA anti-adhesion membrane and its application in tendon anti-adhesion. In this paper, the research progress and modification strategies of PLLA membranes were systematically reviewed from the three dimensions of tissue adaptation, mechanical adaptation, and degradation adaptation. RESULTS: The three-dimensional adaptation of PLLA membrane is optimized by combining materials (such as hydroxyapatite, polycaprolactone), structural design (multilayer/gradient membrane), and drug loading (anti-inflammatory drug). The balance between anti-adhesion and pro-healing is achieved, the mechanical adaptation significantly improve, and degradation is achieved (targeting the degradation cycle to 2-4 weeks to cover the tendon repair period). CONCLUSION In the future, it is necessary to identify the optimal balance point of three-dimensional fitness, unify the evaluation criteria and solve the degradation side effects through the co-design of physicochemical modification and drug loading system to break through the bottleneck of clinical translation.
Tissue Adhesions/prevention & control* ; Polyesters/chemistry* ; Humans ; Biocompatible Materials/chemistry* ; Tendons/surgery* ; Membranes, Artificial ; Tendon Injuries/surgery* ; Wound Healing ; Animals ; Durapatite/chemistry*

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

ObjectiveTo investigate the correlation between the color， odor and volatile components of Paeoniae Radix Alba（PRA） and its processed products， and to examine the effects of different processing methods on the odor and color formation of PRA. MethodThe odor and chromaticity information of PRA， honey chaff-fried PRA and honey bran-fried PRA were identified by electronic nose and colorimeter， and the volatile components in the different processed products of PRA were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and analyzed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， then the differential key flavor components among the three were screened according to the principles of variable importance in the projection（VIP） value>1 and relative odor activity value（ROAV）≥1. Pearson correlation analysis was used to investigate the association between the differential flavor components and the colorimetric values and electronic nose sensors， respectively. ResultAfter being fried with honey chaff and honey bran， the lightness value（L^*） of PRA decreased， and red-green value（a^*） and yellow-blue value（b^*） increased significantly（P<0.05， P<0.01）. The odor differences were mainly reflected in the S1， S2， S4， S5， S6， S8 and S11 sensors， and the results of PCA of the electronic nose indicated that the odor differences among PRA， honey chaff-fried PRA and honey bran-fried PRA were obvious， among which the overall odor intensity of honey bran-fried PRA was higher than that of honey chaff-fried PRA. A total of 47 volatile components were identified from PRA and its processed products， including 21 for PRA， 36 for honey chaff-fried PRA， and 37 for honey bran-fried PRA. Odor analysis revealed that 12， 24 and 22 volatile components may be the key flavor components in PRA， honey chaff-fried PRA and honey bran-fried PRA， respectively. Correlation analysis showed that the L^* of the decoction pieces was negatively correlated with the content of the Maillard reaction products， the a^* and b^* were positively correlated with the content of the Maillard reaction products， the S1 and S8 sensors were negatively correlated with the content of the Maillard reaction products， and the S2， S4， S5， S6 and S11 sensors were positively correlated with the Maillard reaction products. ConclusionThe color of PRA is deepened after being stir-fried with honey chaff and honey bran， and 5-hydroxymethylfurfural， furfural and other components are generated at the same time， which is in line with the theory of burning aroma strengthens the spleen of stir-fried with honey chaff and honey bran. Honey bran-fried PRA has a stronger Maillard reaction than honey chaff-fried PRA， which makes honey bran-fried PRA with a burnt flavor and a dark yellow color， while honey chaff-fried PRA has a sweet flavor and a bright yellow color.

AIM: To investigate the mechanism of action of Qingxuan Runmu Yin(QRY)in the treatment of dry eye(DE)based on transcriptomics and network pharmacology, and to validate the efficacy and key targets of QRY through a animal model of DE.METHODS:RNA-sequencing(RNA-seq)technology was used to detect differentially expressed genes(DEGs)between mice in the DE group and mice in the normal control group, the active ingredients and potential targets of QRY were screened through database, and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were carried out after overlapping the results and obtaining key targets. Additionally, “drug-component-target signaling pathways” network was built and the protein-protein interaction(PPI)was analyzed. Mice were examined for Schirmer I test(SⅠt), tear film breakup time(BUT), and corneal fluorescein staining(FL)every 7 d from the beginning of the animal experiments. Hematoxylin-eosin staining(HE)was performed to observe pathologic changes in mouse corneal tissues. Enzyme linked immunosorbent assay(ELISA), Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)were performed to verify the mRNA and protein expression levels of the core targets in mouse corneal tissues.RESULTS:Totally 2 234 DEGs, 233 active ingredients and 457 related targets of QRY were collected, with a total of 64 key targets obtained. GO function and KEGG pathway results showed that QRY was closely related to inflammatory mediators, and 19 core targets such as interleukin-1β(IL-1β)were screened by PPI network construction; SⅠt, BUT and FL results in the QRY group were statistically significantly different compared with the model group(all P<0.05); HE staining showed that corneal epithelial cell stratification was disordered and the corneal morphology was changed in the model group. However, QRY treatment significantly improved corneal morphology and disordered stratification, with a close morphology to the blank group; ELISA, Western blot and qRT-PCR results showed that the protein expression and RNA levels of IL-1β, IL-6, and tumor necrosis factor(TNF-α)in the QRY group showed a decreasing trend compared with the model group.CONCLUSION: Through the combination of multiple components, multiple targets and multiple pathways, QRY regulated the targets such as IL-6, IL-1β and TNF through quercetin and other main components, thereby inhibiting AGE-RAGE/TNF/IL-17 and other signaling pathways, thus achieving the treatment on DE.

The regulation of the cell cycle is essential for maintaining normal cellular function,especially in the development of diseases such as lung cancer.The cell cycle consists of four major phases(G1,S,G2 and M phases),which are characterized by a series of precise molecular events to ensure proper cell proliferation and division.In lung cancer cells,cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells.G2 and S-phase expressed 1(GTSE1)is a regulatory protein found in the cytoplasm of the cell,which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis.GTSE1 affects cell cycle progres-sion by interacting with cyclin-dependent kinase inhibitor 1A(p21)and maintaining the stability of p21,which in turn inhibits the activity of cyclin-dependent kinase 1/2(CDK1/2).In addition,GTSE1 is also involved in the regulation of tumor protein 53(p53)signaling pathway.With the assistance of mouse double minute 2 homolog(MDM2),GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation,thus affecting cell cycle and cell death-related signaling pathways.This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer,as well as its potential mechanisms involved in cell cycle regulation.

【Objective】 To study the effects of gestational diabetes (GDM) on morphological structure of brain tissue and microribonucleotide (miRNA) expression profile in neonatal mice, and to provide a new research target for the prevention and treatment of abnormal neurodevelopment in GDM progeny. 【Methods】 The pregnant mice were divided into model group and control group,each group consisted of 10 mice. The model group mice established a GDM model by injecting streptozotocin to measure fasting blood glucose (FPG) and random blood glucose (GLU) at different times. Successful molded mice were randomly divided into model group A and model group C, and control mice were divided into control group B and control group D, with 5 mice in each group. The newborn mice in groups A and B were used for hippocampal tissue GeneChip detection and brain morphology structure observation, and group C and D newborn mice were used for qRT-PCR detection of hippocampus tissue expression differences to verify the differentially expressed genes of miRANs obtained by GeneChip screening. After giving birth, the neonatal mice were sacrificed by decapitation, and the brain tissue was dissected to observe the overall morphological structure. The structural changes of hippocampus were observed under HE chromogenic microscope. The Agilent mouse miRNA oligonucleotide gene chip was used to detect the miRNA expression profile of mouse hippocampus, screen differential miRNAs and predict their target genes, and conduct GO analysis and signal transduction pathway analysis of target genes. The relative expression levels of the screened miRNAs were verified by qRT-PCR. 【Results】 Compared with the control group, the GLU increased significantly from the 3rd day after drug administration in the model group (P<0.01). Macroscopic observation of control group B mice had normal brain morphology and structure, smooth appearance, clear gyrus, close arrangement of hippocampus cell structure, uniform staining and complete structure; in model group A, the number of hippocampus cells decreased, loose arrangement and deep staining. In the initial screen of miRNA microarray, there were 11 differentially expressed miRNAs between control and model groups, all of which were downregulated miRNAs, including let-7b-5p、miR-130b-3p、miR-181c-5p、miR-181d-5p、miR-3099-3p、miR-3470a、miR-3473a、miR-3473b、miR-500-3p、miR-532-5p、miR-7047-5p(P<0.05). Two miRNAs (miR-3473b, miR-7047-75p) and 5 target genes (MAPK3, MAPK11, MAPK14, CALM3, AKT3). The relative expression of miR-3473b and miR-7047-5p in model group C were lower than that in control group D (t=19.13 and 6.24, P<0.05), and the validation results were consistent with the microarray test results. 【Conclusion】 Compared with the offspring of normal pregnant mice, GDM offspring mice have abnormal development of brain structure and damage of hippocampal nerve cells, and there are a large number of abnormal expression of miRNAs in hippocampal tissue. Differentially expressed miRNAs can be used as research targets for prevention and treatment of GDM offspring neurodevelopmental abnormalities.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.