Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

The pathogenesis of pulmonary fibrosis (PF) is complex. It is characterized by myofibroblast hyperplasia and deposition of collagen protein. Indoleamine 2,3-dioxygenase 1 (IDO1) is expressed in lung fibroblasts and epithelial cells, but its functions in lung homeostasis and diseases remain elusive. Here, we characterize the critical role of IDO1 in PF patients and bleomycin (BLM)-induced PF mouse models. We find that IDO1 is significantly upregulated in the fibrotic lungs of patients and mice, showing a positive correlation with genes characteristic of fibrosis. Functionally, IDO1 knockout inhibits lung fibroblast proliferation, differentiation, mitochondrial biogenesis, and mitochondrial oxidative phosphorylation. Conversely, IDO1 overexpression and accumulation of kynurenine (Kyn) exacerbate progressive lung fibrosis. Mechanistically, IDO1-deletion activated profound mitochondrial fusion-enhanced potentially the capacity for fatty acid oxidation, along with activation of de novo glycolytic serine/glycine synthesis pathways and mitochondrial one-carbon metabolism. Wedelolactone (WEL), a small molecule IKK inhibitor, is found to strongly bind to IDO1 and effectively protect mice from PF in an IDO1-dependent manner. Collectively, this study characterizes a promotor role for IDO1 in PF and suggests a potential avenue of targeting IDO1 to treat lung diseases.

Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine (TCM), substantially advancing research and development efforts. Spectrum-effect correlation analysis, affinity ultrafiltration, high-content screening (HCS) imaging, and cell membrane chromatography (CMC) have emerged as essential tools, effectively linking TCM chemical constituents to their biological effects, thereby enabling efficient active ingredient screening. Additionally, molecular interaction analysis provides deeper insights into TCM-biomolecule interaction mechanisms, enhancing understanding of its therapeutic potential. Computer-aided techniques facilitate TCM active ingredient identification, optimizing the screening process for efficiency and cost-effectiveness. Molecular probe technology, as an emerging methodology, enables precise and rapid screening for novel therapeutic drug discovery. Ongoing technological advancement in this field indicates promising future developments, potentially leading to more effective and targeted TCM-based therapies.
Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Humans ; Drug Discovery/methods* ; Animals

This study compared the chemical composition differences among various root tissues of Astragalus membranaceus through optimization of histochemical localization methods, thereby providing some reference for targeted extraction and enrichment of bioactive components. The chloral hydrate permeabilization technique was enhanced with sodium nitrite-aluminum nitrate-sodium hydroxide reagent for flavonoid staining. Comparative analyses of total saponins, total flavonoids, and astragaloside IV content in xylem, phloem, and periderm tissues were performed using ultraviolet-visible spectroscopy (UV-Vis) and high-performance liquid chromatography (HPLC). By optimizing staining protocols, interference from natural pigmentation was successfully eliminated, thereby enhancing the visualization of tissue-specific chemical distribution. Quantitative analysis revealed that the phloem contained the highest total saponins (6.92%), while the periderm exhibited peak total flavonoids (0.876%) and exclusive enrichment of astragaloside IV (0.850%). The refined histochemical localization method enables precise characterization of phytochemical distribution across root tissues, which can offer guidance for selective extraction and enrichment strategies, and comprehensively promote the utilization and development of Astragalus membranaceus resources.

Alzheimer's disease is a neurodegenerative disorder characterized by complex and not fully understood pathogenesis.Recent research has revealed that abnormalities in lipid metabolism and inflammatory responses play a crucial role in the development and progression of Alzheimer's disease.This review aims to explore the modulatory effects of lipid metabolism on inflammatory responses and their subsequent influence on the pathological processes of Alzheimer's disease from the aspects of the relationship between dysregulated lipid metabolism,increased inflammatory responses,and Alzheimer's disease,the regulatory effects of lipid mediators,and the role of microglia in these processes.

Objective:To explore the short-term efficacy on 3D printing assisted reconstruction of traumatic digit joint defects using rib and costo-osteochondral autograft.Methods:From August 2022 to July 2023, 7 patients with open digit joint defects had undergone emergency primary debridement and fracture fixation in the Department of Orthopaedics, 988th Hospital of the Joint Logistics Support Force of PLA. Patients with more phalangeal defects that could not be aligned were treated with antibiotic bone cement filling in the emergency surgery. In the second stage surgery, bone cement was removed and transfer of rib cartilage graft was performed to reconstruct the digit joint defect. According to a 1∶1 3D printed hand templates, rib cartilage grafts were crafted to the shape of digit joints, and then spliced together the digit joints and bone defects for fixation. Follow-up X-ray examinations were taken and assessment of the healing status of rib and fractures of phalangeal and metacarpophalangeal bones were carried out according to the Paley fracture healing score. At the outpatient follow-up, assessment of transferred joint movement and evaluation of upper limb function were conducted according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Visual Analogue Scale (VAS) pain scores were evaluated from the affected digits and donor sites.Results:After reconstructive surgery, all 7 patients had primary healing of the wounds of hand. One patient had fat liquefaction at the donor site, and the rest had primary donor site healing. One patient received further surgery for extensor tendon repair after rib cartilage grafting due to the digital extensor tendon injury. All 7 patients were included in postoperative follow-up for 6-11 months, with an average of 9 months. All patients had excellent fracture healing according to the Paley fracture healing score. At the final follow-up, the extension and flexion of the digit joints were found at 40°-80° (average 56.2°) for proximal interphalangeal joints (4 patients), and 10° in extension and 85° in flexion for metacarpophalangeal joint (1 patient). The range of motion of the thumb interphalangeal joint (2 patients) was 20°-35° (average 27.5°). Hand function was assessed according to Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and it was found that 3 patients were in excellent, 3 in good and 1 in fair.Conclusion:This study focused on the treatment of traumatic digit joint defects by transfer of individually crafted rib cartilages in reconstruction of the defected digit joint. It significantly improves the appearance and function of the defected digit joints, especially suitable for the irregular defects of phalangeal bones.

Objective:To investigate the effect and mechanism of esophageal squamous cell carcinoma exosomal miR-181b-5p to the polarization of M2 macrophages.Methods:Extracted and identified exosomes from esophageal squamous cell carcinoma,and detected the expression of miR-181b-5p in esophageal squamous cell carcinoma cells and their exosomes by qRT-PCR.M0 type macro-phages were divided into PBS group,HEEC exo group,Eca-109 exo group,miR-NC exo group,miR-181b-5p exo group,miR-NC group,miR-181b-5p mimic group,si-NC group,si-PTEN group,miR-181b-5p exo+PTEN group.qRT-PCR was used to detect the expressions of CD163,CD206,iNOS and TNF-α in each group.The targeting relationship between miR-181b-5p and PTEN were veri-fied by double luciferase reporter gene experiment.Results:miR-181b-5p was significantly overexpressed in esophageal squamous cell carcinoma cells TE-13,TE-12,TE-10,Eca-109,KYSE30 and their exosomes(P<0.001).Compared with miR-NC group,the expression of CD163 and CD206 in cells were significantly upregulated in the miR-181b-5p mimic group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).The results of double luciferase reporter genes showed that PTEN was the target gene of miR-181b-5p.Compared with si-NC group,the expressions of CD163 and CD206 in cells were significantly upregu-lated in the si-PTEN group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with PBS group,the expressions of CD163 and CD206 in cells were significantly upregulated in the Eca-109 exo group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with miR-NC exo group,the expressions of CD163 and CD206 in cells were significantly upregulated in the miR-181b-5p exo group,as well as the expressions of iNOS and TNF-α were significantly downregulated(P<0.001).Compared with miR-181b-5p exo group,the expressions of CD163 and CD206 in cells were significantly downregulated in the miR-181b-5p exo+PTEN group,as well as the expressions of iNOS and TNF-α were significantly upregulated(P<0.001).Conclusion:Exosomal miR-181b-5p inhibits PTEN expressions to promote M2 macrophage polarization.

Objective To explore the clinical effect of a trapezoidal transparent corneal incision during phacoemulsi-fication.Methods A total of 57 patients(68 eyes)undergoing phacoemulsification were selected and divided into a con-ventional incision group and a trapezoidal incision group using a random number table method.There were 28 patients(34 eyes)in the conventional incision group,including 15 eyes(males)and 19 eyes(females),with an age range of 41-82(65.0±10.1)years;and there were 29 patients(34 eyes)in the trapezoidal incision group,including 21 eyes(males)and 13 eyes(females),with an age range of 46-87(66.0±11.1)years.All patients underwent cataract phacoemulsification combined with intraocular lens(IOL)implantation.A 3.0 mm transparent corneal incision was made for patients in the conventional incision group,while an improved trapezoidal transparent corneal incision was made for patients in the trape-zoidal incision group.The uncorrected visual acuity,intraocular pressure,corneal astigmatism,and incidence of intraoper-ative and postoperative complications were compared between the two groups.Results The uncorrected visual acuity of patients in the trapezoidal incision group was better than that of patients in the conventional incision group at 1 week and 3 months after surgery,and the differences were statistically significant(both P＜0.05).There was no statistically significant difference in intraocular pressure and corneal astigmatism between the two groups of patients at 1 week,1 month,and 3 months after surgery(all P＞0.05).The number of eyes with anterior chamber collapse and the number of eyes requiring a watertight incision in the conventional incision group were greater than those in the trapezoidal incision group during sur-gery,and the differences were statistically significant(both P＜0.05).The number of eyes with incision edema and the number of eyes with incision gap in the conventional incision group were greater than those in the trapezoidal incision group after surgery,and the differences were statistically significant(both P＜0.05).In the conventional incision group,IOL was displaced in 18 eyes due to the shallow anterior chamber and then returned to normal after the formation of the anterior chamber through a watertight incision during surgery;during the formation,iris prolapse and incarceration occurred in 2 eyes,and IOL rotation or incarceration occurred in 3 eyes.In the trapezoidal incision group,3 eyes had a shallow anterior chamber after surgery,and a watertight incision was used to form the anterior chamber;there was no IOL incarceration or displacement or iris prolapse.Conclusion The improved trapezoidal transparent corneal incision can effectively prevent IOL displacement caused by anterior chamber collapse during cataract surgery while ensuring the stability of the anterior chamber.It can also reduce the related complications caused by the watertight incision using a flushing needle and restore patients'vision as early as possible.

Objective:To construct a prediction model for the clinical supply of blood components in Xi′an City from 2023 to 2025.Methods:Based on the blood supply data of the Blood Management Information System of Shaanxi Provincial Blood Center from January 2013 to December 2022, a gray prediction model and an exponential curve fitting model were used to construct the prediction model, and the optimal prediction model was determined according to the error parameters of the relevant indicators of the model. The supply of blood components in Xi′an from 2023 to 2025 was predicted.Results:The fitting equations of the exponential curve fitting model to predict the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were, x（1）（ t+1）=1.16e 0.04t， x（1）（ t+1）=1.04e 0.12t and x（1）（ t+1）=1.01e 1.10t, respectively. The mean absolute errors (mean relative errors) of the exponential curve fitting model in predicting the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were 10 488.7 (0.05%), 2 114.9 (0.08%) and 3 089.6 (0.07%), respectively, which were lower than those of the gray prediction model, about 10 488.7 (3.44%), 2 152.78 (8.20%) and 3 441.35 (7.92%), respectively. The exponential curve fitting model predicted that the clinical supply of blood components in Xi′an would increase year by year from 2023 to 2025, and the clinical supply of suspended red blood cells, platelets, and cryoprecipitate in Xi′an would increase to 409 467 U, 69 818 therapeutic volume and 94 724 U, respectively by 2025. Conclusion:The exponential curve fitting model can make a good prediction of the clinical supply of blood components in Xi′an City.