ObjectiveTo investigate whether Bushen Huoxue prescription improves embryo implantation through regulating exosomal miRNA to enhance maternal-fetal interface communication based on Bushen Huoxue therapy. MethodsIn the animal experiment， all the rats （except for the blank group） were administered hydroxyurea （450 mg·kg^-1） via gavage for 10 d， as well as epinephrine （0.3 mg·kg^-1） and mifepristone （5.5 mg·kg^-1） via subcutaneous injection for 7 d to establish an implantation disorder model of kidney deficiency and blood stasis type. The Bushen Huoxue prescription （BSHX） groups were administered the prescription at different doses （7.30 g·kg^-1 for the high-dose group， 3.65 g·kg^-1 for the medium-dose group， and 1.83 g·kg^-1 for the low-dose group） via gavage. The dydrogesterone group was administered the corresponding medicine （2.63 mg·kg^-1） via gavage. After intervention for 10 days， uterine histopathological changes were observed via hematoxylin-eosin （HE） staining. Mucin （MUC1）， forkhead box protein O1 （FoxO1）， and homeobox A10 （HoxA10） expression levels were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Cell experiment selected primary endometrial epithelial cells （EEC） and trophoblast cells （TC） as research subjects. Exosome-free medicated serum was prepared by ultracentrifugation and cultured in complete medium. Exosomes were isolated from cell supernatants by ultracentrifugation for cross-co-culture. After 48 h， migration and invasion abilities were assessed by scratch and Transwell assays. Sequencing was then performed on EEC-origin exosomal miRNA. ResultsThe model rats exhibited thin endometrium， along with reduced blood vessels， glandules， and pinopode numbers. BSHX improved endometrial morphology and increased pinopode numbers. MUC1， FoxO1， and HoxA10 expressions were downregulated in the model rats， while these parameters were upregulated after BSHX medium- and high-dose intervention. In the cell experiment， after exosome-free medicated serum intervention for 24 h， migration and invasion abilities were enhanced in the BSHX groups （P<0.01）. In EEC-origin exosomal miRNA sequencing， gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses revealed enrichment in biological processes （gastrulation， neuronal differentiation， alongside cell development and regeneration）， involving the mitogen-activated protein kinase （MAPK）， FoxO1， Wnt， mammalian target of rapamycin （mTOR）， and tumor necrosis factor （TNF） signaling pathways. ConclusionBSHX promotes embryo implantation by improving endometrial receptivity via regulating exosomal miRNA. These findings provide potential targets for exosomal miRNA-based assisted reproductive strategies and a novel theoretical basis for infertility treatment by traditional Chinese medicine.

Objective To analyze the efficacy, safety, and learning curve of the three-lobe holmium laser enucleation of the prostate(HoLEP)in the treatment of benign prostatic hyperplasia(BPH)in a county-level hospital.Methods A retrospective analysis was conducted on the clinical data of 65 BPH patients who underwent the three-lobe HoLEP performed by a single surgeon at the Department of Urology, Yining County People's Hospital, during Dec.2023 and Jun.2024.The enucleation efficiency was calculated by dividing the weight of the enucleated prostatic tissue by the enucleation time.A case scatter diagram of enucleation efficiency was plotted according to the chronological order of the operations, and the learning curve was analyzed after fitting.Based on the inflection points of the learning curve, the learning process was divided into the initial learning, mastery, and proficiency phases.The basic clinical data, perioperative indicators, postoperative complications, and follow-up indicators were compared among the different learning phases.Results All 65 procedures were successfully completed.Marked by the enucleation efficiency reaching a plateau, cases 1-20 were defined as the initial learning phase, cases 21-40 as the mastery phase, and cases 41 onwards as the proficiency phase.The prostate volume in the proficiency phase was significantly larger than that in the initial learning and mastery phases(both P＜0.05).There were no statistically significant differences in other baseline characteristics among the three groups(all P＞0.05).The operation time [(105.50±19.12)min vs.(85.25±26.92)min vs.(69.00±23.58)min] and enucleation time [(76.90±14.19)min vs.(63.70±22.24)min vs.(48.80±20.48)min] showed a decreasing trend across the three groups(all P＜0.05).The enucleation efficiency in both the mastery and proficiency phases was significantly higher than that in the initial learning phase [(1.16±0.44)g/min vs.(0.85 ±0.25)g/min, P＜0.05;(1.36±0.49)g/min vs.(0.85±0.25)g/min, P＜0.05].The enucleation efficiency in the proficiency phase was slightly higher than that in the mastery phase, but the difference was not statistically significant(P= 0.389).There was no significant difference in the incidence of perioperative complications among the three groups(all P＞0.05).At the 6-month follow-up, the international prostate symptom score(IPSS), post-void residual(PVR), and maximum urinary flow(Qmax)were significantly improved compared to preoperative values in all three groups(all P＜0.05);however, no significant differences were observed among the three groups(all P＞0.05).Conclusion The three-lobe HoLEP for the treatment of BPH is safe and effective in a county-level hospital setting.Surgeons with some experience in endoscopic surgery can preliminarily master this technique after a learning period of approximately 20 procedures.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

The mandibular condyle is a critical growth center in craniofacial bone development, especially during postnatal stages. Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks. Plagl1, which encodes a zinc finger transcription factor, is a paternally expressed gene. We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell (CNCC)-derived lineage cells in mouse condyles. Using the CNCC-derived lineage-specific Plagl1 knockout mouse model, we evaluate the function of PLAGL1 during postnatal mouse condyle development. Our findings show that PLAGL1 contributes significantly to osteoblast differentiation, and its deficiency impairs osteogenic lineage differentiation, which consequently disrupts mandibular condyle development. Mechanistically, insulin-like growth factor 2 (IGF2) in complex with IGF-binding proteins (IGFBPs) has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis. Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway, leading to disordered glucose metabolism, defective extracellular matrix organization, and impaired ossification. Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency. In conclusion, the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.
Animals ; Osteogenesis/genetics* ; Insulin-Like Growth Factor II/metabolism* ; Mice ; Transcription Factors/metabolism* ; Mice, Knockout ; Cell Differentiation ; DNA-Binding Proteins/genetics* ; Mandibular Condyle/growth & development* ; Osteoblasts/cytology* ; Signal Transduction ; Neural Crest/cytology*

Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

Objective:To establish a set of dynamic definition methods and key operational techniques for community pediatric services contents within the framework of an integrated children health services model.Methods:This was a cross-sectional study. From December 2023 to June 2024, a study was conducted at the Shanghai Gumei Community Health Service Center. The study was divided into three phases: identifying the health needs of community children (Phase A), developing the service content and methods for community children (Phase B), and establishing a community children service network (Phase C). A variety of methods, including questionnaires and focus group interviews, were comprehensively employed in each phase to develop the ABC demand network and its construction approach for community children, and to establish a networked service system.Results:A total of 512 questionnaires were distributed in Phase A, of which 499 were returned for an effective recovery rate of 97.5%. Of the parents, 488 (97.8%, 488/499) would actively seek information related to children′s health. Of those parents, 90.6% (452/499), 80.8% (403/499), and 71.9% (359/499) expressed concern about their children′s growth and development, mental health and social adaptation, and the prevention and treatment of common, frequently occurring diseases, respectively. The research clarified the health needs of children in the community and the health issues of children in different age groups. This included the mental health and social adaptation of community children, as well as common and frequently occurring diseases. The study also revealed a lack of mental health and social adaptation's services for children in the community. After sorting the community′s services into categories such as children′s growth and development detection, diagnosis and treatment of common diseases, and planned immunizations, and establishing corresponding service methods, it was found that Gumei community Health Service Center had strong diagnostic service capabilities for children aged 0-3 and 4-6, but need improved for children aged 7-12 and 13-15. At the same time, a service network consisting of five major categories, represented by medical alliances, has been established to address unmet needs in diagnosis and rehabilitation care for mental health and social adaptation, as well as major diseases.Conclusions:The study has developed an ABC demand network and its construction method for community children. It provides new ideas for defining the content of community pediatric services and establishing supporting methods, and it offers a practical basis for the constructing a community pediatric service system.

Objective To investigate the correlation between insulin resistance and interleukin-6 (IL-6), chemerin, total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low density lipoprotein cholesterol (LDL-C)/HDL-C ratio and insulin resistance in obese patients with type 2 diabetes mellitus (T2DM), and to provide scientific basis for T2DM prevention and control. Methods A total of 355 obese T2DM patients in Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine were selected from January 2021 to December 2023. IL-6, chemerin and lipids were detected, and the assessment of insulin resistance was conducted through the homeostasis model assessment of insulin resistance (HOMA-IR). Results Among the 355 obese T2DM patients, there were 280 cases of insulin resistance, with the incidence rate of 78.87%. The BMI, IL-6, chemerin, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C in the insulin resistance group were higher than those in the non-insulin resistance group (P<0.05). The above insulin resistant patients were divided into 4 subgroups by means of insulin resistance, and there were significant differences in BMI, IL-6, chemerin, and TG/HDL-C among the subgroups (P<0.05). IL-6, chemerin, and TG/HDL-C were positively correlated with HOMA-IR in obese T2DM patients (P<0.05), while TC/HDL-C and LDL-C/HDL-C had no significant correlation with HOMA-IR (P>0.05). BMI, IL-6, chemerin, and TG/HDL-C were all influencing factors of insulin resistance in obese T2DM patients (P<0.05). Conclusion IL-6, chemerin and TG/HDL-C are correlated with insulin resistance in obese patients with T2DM and are influencing factors for the occurrence of insulin resistance.

Objective: To investigate the vitamin D levels in children aged 1 year in Shaoxing City, Zhejiang Province, so as to provide the basis for prevention and treatment of vitamin D deficiency in children and promoting their health. Methods: The 1-year-old children who underwent health examinations at the Department of Child Health Care of Shaoxing Maternal and Child Health Care Hospital from September 2023 to August 2024 were selected. Basic information of the children was collected through the medical record information system, and their length and weight were measured. The length, weight and nutritional status were evaluated according to the Technical Specifications for the Management of Nutritional Diseases in Children. Serum 25-hydroxyvitamin D [25- (OH) D] levels were measured using electrochemiluminescence assay, and vitamin D levels were assessed based on the fifth edition of Child Health Care. The vitamin D levels were analyzed among the children with different genders, testing months, and growth status. Results: A total of 2 245 children were recruited, including 1 189 boys (52.96%) and 1 056 girls (47.04%). The median serum 25- (OH) D level was 39.98 (interquartile range, 16.63) ng/mL. Vitamin D insufficiency was observed in 279 children, with an insufficiency rate of 12.43%. The median serum 25- (OH) D level in boys was 39.26 (interquartile range, 17.75) ng/mL, which was lower than that in girls at 41.39 (17.75) ng/mL (P<0.05). The vitamin D insufficiency rate was 13.04% in boys and 11.74% in girls, with no statistically significant difference (P>0.05). The lowest vitamin D insufficiency rate was observed in August at 4.95%, while the highest rate was in September at 23.89%, showing the statistically significant difference across testing months (P<0.05). The children with above-average length ratings, higher weight ratings and obesity had higher vitamin D insufficiency rates, at 17.29%, 20.86% and 20.88%, respectively. The vitamin D insufficiency rate increased with higher weight and nutritional status ratings (both P<0.05), but no significant change was observed with higher length ratings (P>0.05). Conclusions The vitamin D insufficiency rate among 1-year-old children in Shaoxing City was 12.43%, with variations observed in different testing months, weight and nutritional status. Targeted prevention and intervention measures should be implemented to address these differences.

To explore the chemical constituents of Ecballium elaterium and their cytotoxicity, this study employed multiple chromatographic techniques including normal-phase silica gel, MCI, octadecylsilyl(ODS), Sephadex LH-20 gel, and semi-preparative liquid chromatography for compound isolation from its active fraction. A total of 12 compounds were obtained, and they were identified according to the analysis of a variety of spectral data and literature comparison as 24Z-20,27-dihydroxy-16α,23α-epoxy-cucurbita-2-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside(1), cucurbitacin R(2), cucurbitacin B(3), cucurbitacin D(4), cucurbitacin I(5), cucurbitacin L(6), dehydrodiconiferyl alcohol(7), 3-hydroxy-4-methoxycinnamic acid(8), ferulaic acid(9), p-coumaric acid(10), rutin(11), and lariciresinol-4'-O-β-D-glucoside(12), among which compound 1 was a new compound. Compounds 2-6 had strong cytotoxicity against human lung carcinoma A549 cells with the IC_(50) values of(0.48±0.09),(0.03±0.002),(0.13±0.03),(0.87±0.14),(0.15±0.03) μmol·L~(-1), respectively, which were stronger than the positive control doxorubicin \[IC_(50)=(3.92±1.60) μmol·L~(-1)\].
Humans ; Drugs, Chinese Herbal/toxicity* ; Cell Line, Tumor ; Cucurbitaceae/chemistry* ; Cell Survival/drug effects*