Three-dimensional(3D)printing technology represents an additive manufacturing process wherein computer-aided designs are materialized through the sequential layering of materials by 3D printers, culminating in the formation of complete objects. Since its inception, this technology has found extensive application across various clinical domains, notably enhancing outcomes in surgical assistance. Recently, the utilization of 3D printing in ophthalmic plastic surgery has gained momentum, with researchers conducting numerous valuable explorations into the design of ophthalmic plastic surgeries, the development of surgical fillers for ophthalmic plastic orbital conditions, and the customized design of auxiliary devices for bothoncological and non-oncological lesions. Despite the majority of these studies being confined to the conceptual design phase or limited to case studies, 3D printing technology has demonstrated unparalleled advantages in elevating therapeutic efficacy and surgical precision. To encapsulate the current state and future research directions of 3D printing technology within the realm of ophthalmic plastic surgery, this article aims to review its applications in this field, with the intention of providing a reference for pertinent clinical investigations.

Three-dimensional(3D)printing technology represents an additive manufacturing process wherein computer-aided designs are materialized through the sequential layering of materials by 3D printers, culminating in the formation of complete objects. Since its inception, this technology has found extensive application across various clinical domains, notably enhancing outcomes in surgical assistance. Recently, the utilization of 3D printing in ophthalmic plastic surgery has gained momentum, with researchers conducting numerous valuable explorations into the design of ophthalmic plastic surgeries, the development of surgical fillers for ophthalmic plastic orbital conditions, and the customized design of auxiliary devices for bothoncological and non-oncological lesions. Despite the majority of these studies being confined to the conceptual design phase or limited to case studies, 3D printing technology has demonstrated unparalleled advantages in elevating therapeutic efficacy and surgical precision. To encapsulate the current state and future research directions of 3D printing technology within the realm of ophthalmic plastic surgery, this article aims to review its applications in this field, with the intention of providing a reference for pertinent clinical investigations.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Objective:To evaluate the application of a two-stage sequential nutritional therapy combined with functional exercise in the preoperative prehabilitation of patients with high-output intestinal fistula(HIF).Methods:A total of 164 HIF patients scheduled for definitive fistula resection in the Department of General Surgery,Eastern Theater Command General Hospital from March 2023 to March 2025 were prospectively enrolled.They were randomly assigned to a control group or an intervention group at a 1:1 ratio,with 82 patients in each group.The control group received conventional nutritional support and basic functional exercise,while the intervention group underwent a two-stage sequential nutritional therapy combined with graded functional exercise.Nutritional indicators,inflammatory markers,functional status,and postoperative recovery were compared between the two groups at 28 days before surgery,1 day before surgery,and 1,3,and 7 days after surgery.Results:On the day before surgery,the nutritional indicators in the intervention group,including albumin[(36.8±4.1)g/L],prealbumin[(213.5±42.1)mg/L],and total protein[(69.3±6.1)g/L],were all significantly higher than those in the control group[albumin(33.1±3.9)g/L,prealbumin(163.2±37.6)mg/L,total protein(63.7±5.9)g/L],with P<0.001.The energy compliance rates on the 21st day before surgery and the day before surgery in the intervention group(85.2%,92.8%)were significantly higher than those in the control group(62.5%,72.4%),with P<0.001.The 6-minute walk distance(6MWD)in the intervention group on the day before surgery and on the 7th day after surgery[(385.1±55.2)m,(346.3±48.4)m]was significantly greater than that in the control group[(315.3±60.7)m,(298.3±51.1)m],with P<0.001.On the 1st day after surgery,the inflammatory markers in the intervention group[CRP(98.7±35.2)mg/L,IL-6(45.3±12.5)pg/mL,PCT(1.2±0.5)ng/mL]were all significantly lower than those in the control group[CRP(152.4±48.6)mg/L,IL-6(89.6±25.4)pg/mL,PCT(2.8±0.9)ng/mL],with P<0.001.Additionally,the time to first ambulation after surgery[(16.8±4.2)h],time to first flatus[(52.4±14.5)h],and ICU stay duration[(3.1±1.6)d]in the intervention group were all significantly shorter than those in the control group,with P<0.001 Conclusion:The two-stage sequential nutritional therapy combined with functional exercise significantly improves the attainment of nutritional targets,suppresses systemic inflammatory response,enhances muscle reserve and exercise tolerance,and effectively shortens the postoperative recovery period in HIF patients.These findings support the use of this combined approach as a targeted and feasible model for preoperative prehabilitation,demonstrating substantial clinical application value.

Objective:To evaluate the safety and clinical efficacy of enteral nutrition (EN) initiated within 24 h after heart transplantation in pediatric patients.Methods:A retrospective cohort study was conducted. Clinical data from 16 pediatric heart transplant recipients at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital between October 2022 and October 2024 were collected, including demographics, anthropometric measurements, biochemical markers, cytokine levels, and clinical outcomes. Based on the timing of EN initiation, the patients were divided into EN-initiated within 24 h and EN-initiated after 24 h 2 groups. Demographic data, preoperative extracorporeal membrane oxygenation (ECMO) support, physical examination indicators, laboratory parameters, and cytokine levels were compared between groups using independent samples t-test, Mann-Whitney U test, Fisher′s exact probability test. Results:The cohort comprised 16 patients (10 males and 6 females) with an age of (12.5±1.9) years. The EN-initiated within 24 h group comprised 6 cases, and the EN-initiated after 24 h group comprised 10 cases. No significant difference was observed between the two groups in age, preoperative body mass index Z-score, preoperative ECMO support, physical examination indicators, laboratory parameters (total protein, albumin, hemoglobin), or cytokine levels (all P>0.05). Compared to the EN-initiated after 24 h group, the EN-initiated within 24 h group exhibited a shorter intensive care unit stay ( t=2.65, P<0.05) and shorter mechanical ventilation duration ( t=2.23, P<0.05) than EN-initiated after 24 h group. Total hospitalization length had no significant difference ( P>0.05). At 72 h post-transplant, the EN-initiated within 24 h group had a lower interleukin-12 P70 ( t=2.46, P<0.05) and interferon-γ levels ( t=2.55, P<0.05) than EN-initiated after 24 h group. Prior to discharge, the EN-initiated within 24 h group has a lower mean skinfold thickness ( t=2.49, P<0.05) and lower mid-upper arm circumference ( t=2.36, P<0.05) compared with the EN-initiated after 24 h group. Conclusions:Initiating EN within 24 h postoperatively is safe and feasible in pediatric heart transplant recipients. Early EN may shorten the length of intensive care unit stay and mechanical ventilation while attenuating postoperative release of inflammatory cytokine.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.