Cancer is a severe threat to human life and health.The over-activation of oncogenes is the main reason for poor treatment and prognosis of cancer patients.Most of these over-activated oncogenes are protein tyrosine kinase(PTK).Among many PTKs,non-receptor tyrosine kinase(NRTK)is an important signaling molecule that regulates cell proliferation and migration as the primary driver of intracellular signaling pathway transduction.Targeting NRTK has become the focus and difficulty in developing anti-tumor drugs.Traditional Chinese medicine(TCM),with its characteristics of multi-channel,multi-link,multi-target,and low toxicity,plays a significant advantage in treating adjuvant tumors.So far,it has been found various traditional TCM monomers can inhibit NRTK from playing an anti-tumor role.This review summarized the part of Src,Jak,Abl,Fak families,the prominent members of NRTK in tumor progression,as well as the TCM monomers acting on these members.We aimed to provide a theoretical basis for the anti-tumor therapy targeting NRTK and a reference for the search for TCM monomer inhibitors of NRTK.

Objective:To characterize the biomechanics of distal dynamic locking and distal static locking of proximal femur bionic nails (PFBN) in fixation of intertrochanteric fractures by a finite element analysis.Methods:The CT image data from the hip to the upper tibia from an adult male volunteer were used to establish a three-dimensional model of the femur by Mimics 20.0 and Geomagic 2013 which was processed further into a model of Evans type I intertrochanteric fracture by software NX 12.0. With reference to the internal fixation parameters commonly used, 4 models of PFBN fixation were established: distal single transverse nail dynamic locking (model A), single oblique nail dynamic locking (model B), single nail static locking (model C) and double nail dynamic locking (model D). Abaqus 6.14 software was used to load and analyze the internal fixation stresses and displacements of fracture ends.Results:Under a 2100N loading, the peak stress was located upon the main nail in the 4 models. The smallest peak stress upon the main nail was in Model D (161.9 MPa), decreased by 15.9% compared with model A (192.5 MPa), by 15.6% compared with model B (191.9 MPa), and by 0.9% compared with model C (163.3 MPa). The peak stress upon the fixation screw was the largest in model A (95.3 MPa), the smallest in model B (91.5 MPa), and 91.5 MPa and 92.2 MPa in models C and D, respectively. The overall displacements of the implants, in a descending order, were 10.14 mm in model A, 10.10 mm in model B, 10.09 mm in model C, and 10.05 mm in model D. Similarly, the displacements of fracture ends were 0.125 mm in model A, 0.121 mm in model B, 0.110 mm in model C, and 0.098 mm in model D.Conclusion:Compared with dynamic locking, distal static locking of PFBN provides a better mechanical stability and reduces stress concentration upon internal fixation.

Objective To explore the clinical efficacy of two procedures in thoracoscopic anterior mediastinal tumor resection. Methods A retrospective study was conducted on patients who underwent thoracoscopic anterior mediastinal tumor resection at the Department of Thoracic Surgery, the 910th Hospital of Joint Logistics Support Force from October 2016 to January 2024. Patients were divided into two groups according to the surgical approach: a modified approach group (bilateral intercostal ports+two subcostal ports) and a classic subxiphoid approach group (one subxiphoid port+two subcostal ports). Perioperative data and postoperative improvement of myasthenia gravis (MG) subgroup were compared between the two groups. Results A total of 55 patients were included, including 27 males and 28 females with a mean age of (49.4±15.1) years. There were 23 patients in the modified approach group and 32 patients in the classic subxiphoid approach group. The modified approach group had shorter operation time [(129.0±20.5) min vs. (148.9±16.7) min, P<0.001], less intraoperative blood loss [(63.0±16.6) mL vs. (75.0±10.8) mL, P<0.001], shorter postoperative drainage tube removal time [(3.1±0.4) d vs. (3.9±0.6) d, P<0.001] and shorter postoperative hospital stay [(4.2±0.4) d vs. (5.0±0.6) d, P<0.001), and lower proportion of intraoperative cardiac dysfunction [4 (17.4%) vs. 14 (43.8%), P=0.040]. There was no statistical difference in maximum diameter of tumor resected [(4.5±1.7) cm vs. (4.0±0.9) cm, P=0.193] and postoperative drainage volume [(396.4±121.5) mL vs. (399.9±161.3) mL, P=0.932]. There was 1 patient of perioperative collateral injury in the modified approach group (pericardial injury), and 6 patients in the classic subxiphoid approach group (1 patient of diaphragm injury, 1 patient of liver contusion, 4 patients of pericardial injury). There was no statistical difference in pain scores at 24 h, 48 h and 72 h after surgery (P>0.05). The postoperative improvement of MG symptoms in the modified approach group was better than that in the classic subxiphoid approach group at 1 year after surgery (complete stable remission rate: 77.8% vs. 50.0%; effective rate: 100.0% vs. 91.6%). No conversion to open chest surgery occurred in either group, and there were no postoperative rehospitalizations or deaths related to surgery within 30 days after surgery in both groups. Conclusion The modified approach is safe and controllable with more open surgical field and more reliable complete resection range than the classic subxiphoid approach group.

Objective To compare the short-term clinical effects of unilateral dual-channel endoscopic discectomy(UBED)and percutaneous endoscopic intervertebral discectomy(PEID)in the treatment of L5S,Lumbar disc herniation,LDH.Methods From January 2019 to January 2021,a total of 57 cases of L5S,LDH treated by UBED or PEID were analyzed retrospectively,including 30 cases in UBED group and 27 cases in PEID group.The operation time,intraoperative fluoroscopy times,postoperative hospitalization days and surgical complications were compared between the two groups.The visual analogue scale(VAS)and oswestry disability index(ODI)were used to compare the postoperative quality of life of the two groups,and the modified MacNab criteria was used to evaluate the clinical efficacy in the last follow-up.Results The operation time of UBED group and PEID group was(75.30±8.44)minutes and(68.37±4.63)minutes,respectively,and the difference between the two groups was statistically significant(P＜0.05).VAS and ODI of 1 week,3 months,1 year and 1.5 years after surgery in 2 groups were significantly decreased compared with those before surgery,with statistical significance(P＜0.05).The VAS score of low back pain in UBED group was higher than that in PEID group[(3.87±1.14)points vs(2.70±0.67)points]at 1 week after surgery(P＜0.05),and there was no significant difference in VAS and ODI at the other time points(P＞0.05).There was no statistical difference in the results of modified MacNab criteria in the last follow-up(P＞0.05).There were 2 cases of dural tear in PEID group,1 case of dural tear in UBED group and 1 case of temporary nerve root injury in PEID group after operation,all of which were cured after symptomatic treatment.Conclusion Compared with PEID,UBED has a longer operation time,more trauma and more obvious low back pain in the short term after operation.The short-term curative effect of the two operations on L5S1 LDH is similar,the incidence of complications is low,and the times of fluoroscopy are few.Both operations are safe and effective.

After more than ten years of development, retinal organoid (RO) based on pluripotent stem cells can highly simulate the development process of human retina, provide insight into the mechanism of retinal development and provide new treatments for retinal diseases.At present, RO has been widely used in the research of the mechanism and treatment of retinal diseases, especially in retinitis pigmentosa (RP).This review summarizes the methods of preparing RO from human pluripotent stem cells, and elaborates the mechanism and therapeutic application of RO-RP disease model in different mutated genes such as PRPF31, RPGR, CRB1, RP2, IMPG2, NR2E3, USH2A, PDE6B and TRNT1, as well as the research progress of RO in drug screening, drug toxicity testing, gene therapy and cell therapy, and discusses the research and application challenges of RO.

Objective To investigate the effects and potential mechanisms of Marsdeniae Tenacissimae Caulis(Tongguanteng)injection and extract in human osteosarcoma cells proliferation,migration,invasion,and apoptosis.Methods MNNG/HOS,Saos-2 osteosarcoma cells,and normal bone marrow mesenchymal stem cells(BMSC)were cultured in vitro.Cells were incubated with different concentrations of Tongguanteng injection and Tongguanteng extract(40,60,80 mg/mL).Cell proliferation was evaluated by CCK-8 assay and plate colony formation assay.Cell migration and invasion were evaluated by scratch assay and Transwell assay.Cell apoptosis was evaluated by Hoechst33342 staining and Annexin-V/PI double staining assay.Bax,Bcl-2 and Caspase-3 mRNA expression were detected using RT-qPCR.The protein expressions of JAK1,p-JAK1,STAT3,p-STAT3 and MMP9 were detected by Western blot.Results Compared with the control group,both Tongguanteng injection and extract significantly decreased the survival rate of MNNG/HOS and Saos-2 cells,inhibited cell clone formation,migration,and invasion,induced cell apoptosis(P<0.05,P<0.01),promoted Bax mRNA and protein expression,inhibited Bcl-2 mRNA and protein expression,and up-regulated Caspase-3 mRNA and Cleaved Caspase-3 protein expression.Tongguanteng injection could significantly down-regulate the expressions of p-JAK1,p-STAT3 and MMP9 protein expression in Saos-2 cells(P<0.05,P<0.01).Conclusion Both Tongguanteng injection and Tongguanteng extract can significantly inhibit proliferation,migration and invasion of human osteosarcoma MNNG/HOS and Saos-2 cells,and induce apoptosis,with no significant difference in anti-tumor effect.The mechanism may be related to the inhibition of the activation of JAK1/STAT3 signaling pathway.

Objective To explore the mechanism of Marsdenia tenacissima in the treatment of breast cancer through network pharmacology and experimental verification.Methods Literature retrieval was conducted to obtain the active components of Marsdenia tenacissima.The SwissTargetPrediction database was used to predict the potential targets of these active components.Targets of breast cancer were obtained from GeneCards,GEPIA2,OMIM,PharmGKB and TTD databases.The intersection targets were obtained,and a Marsdenia tenacissima-breast cancer-targets network was constructed using Cytoscape 3.9.0 software.The core targets were identified through protein-protein interaction(PPI)network analysis,followed by GO and KEGG pathway enrichment analysis to screen relevant signaling pathways.Molecular docking validation was performed for the top 10 key targets and major active components.The human breast cancer cell line MDA-MB-231 was treated with Marsdenia tenacissima injection in vitro.Cell proliferation ability was detected by CCK-8 assay and colony formation assay.Cell apoptosis was detected by Calcein-AM/PI staining and flow cytometry.Cell migration ability was detected by Transwell assay.Western blot experiment was used to validate the PI3K-AKT signaling pathway.Results Totally 37 active components and 276 potential targets against breast cancer were screened from Marsdenia tenacissima,including 11alpha-O-Benzoyl-12beta-O-acetyl tenacigenin B,Caffeic acid,Drevogenin A and Kaempferol.25 core targets were screened by PPI network such as AKT1,EGFR,TNF,CTNNB1 and IL-6,which mainly affected the estrogen signaling pathway,ErbB signaling pathway,HIF-1 signaling pathway and PI3K-AKT signaling pathway,etc.The molecular docking results showed that the main active components of Marsdenia tenacissima exhibited good binding activities with the core targets AKT1,ALB,CASP3,ESR1 and TNF.The results of in vitro experiments showed that Marsdenia tenacissima injection could inhibit the proliferation and migration ability of MDA-MB-231 cells(P<0.01,P<0.001)and induce apoptosis(P<0.001),as well as inhibit the activation of PI3K-AKT signaling pathway(P<0.05,P<0.01).Conclusion Marsdenia tenacissima may exert its anti-breast cancer effects through multiple targets and pathways,and the mechanism may be related to the inhibition of PI3K-AKT signaling pathway.

As an optional method for the treatment of hypospadias, free tube graft urethroplasty has been applied in some centers in recent years. It has the advantages of convenient urethra materials, high freedom of surgery, and satisfactory urine flow and appearance, but there are fewer reported cases and many complications. Therefore, it is recommended to be used cautiously. This paper summarizes the experience of 497 cases of free surgical surgery based on Buck fascia reconstruction, including key points such as full correction of penile lower curvature, no tension-free urethra, long-inclined plane anastomosis, and reliable coverage enhancement.

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

Paclitaxel is the first-line chemotherapy drug for a variety of cancers. However， the paclitaxel resistance greatly reduced the efficacy in the later treatment stage， which seriously increased the mortality and recurrence rate of cancer and limited the clinical application of paclitaxel. At present， Chinese medicine compound prescription， proprietary Chinese medicine， and Chinese medicine injection are widely used as the adjuvant chemotherapy drugs for the treatment of cancer in clinic. Chinese medicine has shown unique advantages in improving the efficacy of chemotherapy drugs and the prognosis of chemotherapy， and reducing the toxic and side effects. However， the specific mechanism and effective monomer composition of Chinese medicine for reversing the resistance of chemotherapy drugs are unclear， and the application of Chinese medicine in different types of cancer is also limited， which are worthy of further exploration. This review summarized the composition of Chinese medicine monomer with synergistic antitumor effect combined with paclitaxel in recent years. The specific mechanism and pharmacological activities of Chinese medicine monomer reversing paclitaxel resistance were classified. This review found that through acting on the membrane transport protein， Chinese medicine monomer promoted the accumulation of paclitaxel in tumor cells， inhibited the expressions of protein and metabolic enzyme related to multidrug resistance and the metabolism of paclitaxel， and regulated the levels of apoptosis genes and factors and apoptosis-related pathways to promote the inhibitory effect of paclitaxel on cell proliferation. Chinese medicine monomer also significantly improved paclitaxel chemotherapy sensitivity by regulating the expression levels of micro ribonucleic acid （microRNA） and long non-coding ribonucleic acid RNA （lncRNA）， inhibiting the characteristics of tumor stem cells and tumor metabolic reprogramming， improving tumor microenvironment， and triggering tumor cell death autophagy and oxidative stress response. This review provides a theoretical basis for clarifying the specific anti-tumor mechanism of Chinese medicine monomer combined with paclitaxel， which is of great significance for the development of new Chinese medicine and the clinical research of the drugs combined with paclitaxel， and has certain value for the application of Chinese medicine combined with other chemotherapy drugs.