BACKGROUND:Endometrial receptivity is a key factor in embryo implantation in northwest Tibetan cashmere goats,and the expression of genes related to endometrial receptivity and their variable splicing are still unclear. OBJECTIVE:To analyze and explore genes and variable splicing events related to endometrial receptivity in northwest Tibetan cashmere goats. METHODS:On days 5 and 15 of pregnancy(representing pre receptive endometrium group and receptive endometrium group),three northwest Tibetan cashmere goats were randomly selected.Endometrial tissue was collected and stained with hematoxylin and eosin to observe tissue morphology.Immunohistochemical staining was used to detect the expression of endometrial receptive marker proteins leukemia inhibitory factor and vascular endothelial growth factor.After the total RNA was extracted and the quality test was qualified,transcriptome sequencing was performed to search differentially expressed mRNAs,lncRNAs,circRNAs,and miRNAs,perform functional prediction,and analyze alternative splicing mRNAs and lncRNAs related to endometrial receptivity. RESULTS AND CONCLUSION:(1)Compared with the pre receptive endometrium group,the expression levels of leukemia inhibitory factor and vascular endothelial growth factor proteins in the endometrial tissue of the receptive endometrium group were significantly increased.(2)The sequencing results showed that the differentially expressed genes were mostly mRNA and lncRNA genes,including 250 upregulated mRNAs,193 upregulated lncRNAs,135 downregulated mRNAs,and 123 downregulated lncRNAs,which were significantly enriched in the Wnt,Hedgehog,and Hippo signaling pathways.(3)Alternative splicing event analysis uncovered 8 differentially expressed variable splicing transcripts,which were all mRNA transcripts,including 2 downregulated and 6 upregulated,and were significantly associated with vascular endothelial growth factor receptor signaling,cell motility,and embryonic development.

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

OBJECTIVE: To investigate the biomechanical characteristics of retrograde tibial nailing (RTN) and distal tibial L-shaped plating in the internal fixation of distal tibial fractures. METHODS: Fourteen fresh adult tibia specimens were selected, comprising 7 males and 7 females aged from 34 to 55 years old. The specimens were randomly divided into experimental group and control group by numerical table method with 7 specimens in each group. RTN was used for internal fixation of distal tibial fractures in the experimental group, and L-shaped plate was used for internal fixation of distal tibial fractures in the control group. The axial compression properties of the two groups of specimens were tested under the pressure of 100, 200, 300, 400, and 500 N after operation, and torsional resistance at torque levels of 1.0, 2.0, 3.0, 4.0, 5.0 N·m. The anti-fatigue performance of the specimens was tested at 500 N pressure for 3 000 and 10 000 cycles. X-ray fluoroscopy was performed to observe whether the the internal fixator was deformed and whether the screw was loosened or broken. RESULTS: When the pressure was 400 N and 500 N, the axial compression displacement of the experimental group was (1.11±0.06) mm and (1.24±0.05) mm, which were smaller than those of the control group (1.21±0.08) mm and (1.37±0.11) mm, and the differences were statistically signific (P<0.05). Under the pressure of 500 N, the axial compression stiffness of the experimental group was (389.24±17.79) N·mm^-1, which was significantly higher than that of the control group (362.37±14.44) N·mm^-1(P<0.05). When the torque was 4 and 5 N·m, the torsion angles of the experimental group were (2.97±0.23) ° and (3.41±0.17) °, which were smaller than those of the control group (3.31±0.28) ° and (3.76±0.20) °, and the differences were statistically significant (P<0.05). When the torque was 5 N·m, the torsional stiffness of the experimental group was (1.48±0.07) N·m per degree, which was higher than that of the control group (1.36±0.06) N·m per degree, and the difference was statistically significant (P<0.05). For the intragroup comparison of fatigue resistance, the differences in axial compression displacement between the two groups were not statistically significant at 3 000 and 10 000 cycles (all P>0.05). When 3 000 times and 10 000 times of compression, the axial compression displacement of the experimental group was (1.38±0.08), (1.43±0.07) mm, which was smaller than that of the control group (1.51±0.10), (1.54±0.08) mm, the differences were statistically significant (P<0.05). In the experimental group, no screw loosening, fracture or internal fixation deformation was found, while in the control group, locking screw loosening occurred in 2 models after 10 000 pressures. CONCLUSION The biomechanical performance of RTN is obviously better than that of the distal tibial L-shaped plate, which provides biomechanical data support for the clinical application of RTN.
Humans ; Female ; Male ; Adult ; Tibial Fractures/physiopathology* ; Middle Aged ; Biomechanical Phenomena ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Bone Nails ; Tibia/surgery*

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To evaluation the bioequivalence of telmisartan tablets(80 mg)between test formulation and reference formulation in Chinese healthy subjects.Methods A single-center,randomized,open-label,two-preparations,single administration,partial repeat crossover of three sequences in three postprandial cycles and complete repeat crossover of two sequences in four fasting cycles,bioequivalence test was designed.Chinese healthy subjects were included in the bioequivalence trial,with 33 randomly assigned to the postprandial group and 32 randomly assigned to the fasting group.In each period,blood samples was collected before and after administration.The plasma concentration of the drug was determined by LC-MS/MS,using WinNonlin version 8.3 calculate the pharmacokinetic parameters and perform a statistical analysis using SAS version 9.4.Results The main pharmacokinetic parameters of telmisartan tablets after oral administration of test or reference were as follows.Fasting group Cmax were(556.10±456.06)and(580.99±533.50)ng·mL-1;AUC0-t were(3 475.15±3 785.16)and(3 450.54±3 681.02)ng·mL-1·h;AUC0-∞ were(3 214.06±2 272.06)and(3 194.84±2 187.45)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Postprandial group Cmax were(299.26±124.72)and(291.29±126.34)ng·mL-1;AUC0-t were(3 682.24±2 799.72)and(3 636.71±2 158.42)ng·mL-1·h;AUC0-were(3 544.53±1 553.06)and(3 969.38±2 528.22)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Conclusion Under fasting and fed conditions,two kinds of telmisartan tablets are bioequivalent in Chinese healthy subjects.

Objective:To investigate the clinical efficacy of three-connections and four-screwings technique in the treatment of high double column acetabular fractures through a single ilioinguinal approach.Methods:A retrospective study was conducted to analyze the data of 42 patients who had been treated for high double column acetabular fractures from June 2017 to June 2020 at Trauma Ward 2, Department of Orthopedics and Traumatology, The First Hospital of Traditional Chinese Medicine of Changde. There were 19 males and 23 females with an age of (42.7±25.6) years. 29 injuries were due to a traffic accident, 12 ones to fall from a height, and one to fall. The time from injury to operation was (4.5±2.1) days. All the patients were treated by the three-connections and four-screwings technique through a single ilioinguinal approach. Briefly, the anterior column was connected and secured to the main bone using 3 routes, and the posterior column was attached and fixated to the anterior column reset using 2 or 3 of the 4 screwings. The operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, hip function at the last follow-up and complications during the follow-up were recorded.Results:For this cohort, the operation time was (150.0±30.5) min, and intraoperative blood loss (300.0±50.0) mL. According to the Matta scale for postoperative acetabular fracture reduction, 34 cases were excellent, 6 cases good, and 2 cases acceptable, with an excellent and good rate of 95.2% (40/42). After operation one patient had fat liquefaction and wound exudation which responded to drainage and dressing change. The 42 patients were followed up for (15.0±3.4) months. All fractures healed after (11.0±2.0) months. By the modified Merle d'Aubigné & Postel scoring system, the hip function was evaluated at the last follow-up as excellent in 33 cases, as good in 6 cases, and as fair in 3 cases, yielding an excellent and good rate of 92.9% (39/42).Conclusions:In the treatment of high double column acetabular fractures, the three-connections and four-screwings technique through a single ilioinguinal approach can lead to fine reduction and rigid fixation by lag screw compression and neutralization plate protection. Consequently, early functional exercises can be performed to secure good therapeutic outcomes for the patients.

Objective To analyze the correlations of the expressions of miR-4500 and nerve growth factor(NGF)in breast cancer patients with preoperative magnetic resonance(MR)signs.Methods A total of 105 patients with breast cancer admitted to our hospital were selected,the mRNA expression levels of miR-4500 and NGF in breast cancer tissues and adjacent tissues of patients were detected by qRT-PCR,and the positive expression rates of NGF in breast cancer tissues and adjacent tissues were determined by immunohistochemistry method.The correlations of the expressions of miR-4500 and NGF in breast cancer tissues with clinicopathological features and MR signs of patients were analyzed.The targeting relationship between miR-4500 and NGF was predicted by the bioinformatics website,and the correla-tion between the expressions of the two was analyzed.Results Compared with the adjacent tissues,the expression level of miR-4500 in breast cancer tissue decreased(P<0.05),while the level of NGF mRNA and the positive expression rate of NGF increased(P<0.05).There was no significant difference in age,pathological type,tumor classification,parenchymal background,apparent diffusion coefficient or enhancement curve among different expressions of miR-4500 and NGF(P>0.05).The histological grade,lymph node metastasis,tumor diameter,tumor morphology,ring-like enhancement,and peritu-moral brain edema were related to the expressions of miR-4500 and NGF(P<0.05).The bioinformatics website prediction showed that miR-4500 and NGF had binding sites,and the expressions of miR-4500 and NGF mRNA in breast cancer tissues were negatively correlated(r=-0.576,P<0.05).Conclusion The expression of miR-4500 in breast cancer tissue is low,and the expression of NGF is high,which are correlated with the preoperative MR signs in patients,providing a molecu-lar basis for MR signs.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Cells are the fundamental structural and functional units of biological organisms,with inherent differences in composition and interactions with exogenous substances,known as cellular heterogeneity.Single cell inductively coupled plasma-mass spectrometry(SC-ICP-MS)allows for the high-throughput introduction of individual cells,enabling the highly sensitive detection and quantification of elements within a single cell,thus effectively providing information on cellular heterogeneity.This review outlined the SC-ICP-MS sample preparation process for different types of cells(single-cell systems,aggregation-prone and adherent cell systems,animal tissues,and plant tissues),including steps such as separation,washing,and fixation,as well as the advantages and existing issues of the current sample introduction systems and quantification methods.The recent applications of SC-ICP-MS in detecting endogenous substances(endogenous elements and proteins),exogenous substances(heavy metals,metal-based drugs and nanoparticles),and the simultaneous detection of both endogenous and exogenous substances were summarized.Finally,the perspectives on the future development of SC-ICP-MS in analytical methods and application fields were presented,including the optimization of single-cell sample preparation,transport efficiency,evaluation standards of ionization efficiency,and the establishment of multiparametric cell analysis platforms.