OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Objective To explore the clinical application value of contrast-enhanced ultrasound in the differential diagnosis of testicular masses.Methods A total of 63 patients at the First Affiliated Hospital of Wenzhou Medical University with testicular masses from January 2014 to August 2024 were sellected.All patients underwent both conventional ultrasound and contrast-enhanced ultrasound examinations.Among them,pathological results were obtained through surgical resection in 55 cases,and 8 non-tumorous patients were diagnosed through clinical follow-up.According to the results,testicular masses were classified into neoplastic and non-neoplastic lesions.Neoplastic lesions were further divided into benign and malignant masses.The routine ultrasound parameters,serum tumor markers and ultrasound contrast parameters were analyzed.Results In the differential diagnosis between neoplastic and non-neoplastic lesions of the testis,there were significant statistical differences in the maximum diameter of the mass,blood flow grade,enhancement time,and enhancement intensity(P<0.05).In the differential diagnosis between benign and malignant testicular masses,significant statistical differences were found in mass location,maximum diameter of the mass,echo characteristics,blood flow grade indicators,enhancement time,and enhancement intensity(P<0.05).Conclusion Contrast-enhanced ultrasound may have certain reference value in the diagnosis of testicular masses.Hypo-enhancement or non-enhancement,along with slow enhancement,may be manifestations of benign lesions.

BACKGROUND:Synthetic polymers,such as polypropylene and polyester,used for the treatment of abdominal wall defects not only lack biodegradability and bioactivity but also fail to meet the demands of complex and irregular wounds.Therefore,finding bioactive materials with low immunogenicity and good histocompatibility has become a hot spot in the repair of abdominal wall defects. OBJECTIVE:To prepare methacryloyl modified dermal extracellular matrix hydrogel and explore its potential application in abdominal wall defect. METHODS:(1)The porcine dermis was acellular with 0.25%trypsin and 1%Triton X-100 in turn to obtain the dermal extracellular matrix.After pepsin digestion and methacrylic anhydride modification,the methacrylated dermal extracellular matrix hydrogel was formed by photocrosslinking.The microscopic morphology of the hydrogel was observed by scanning electron microscope,and its rheological properties,swelling properties and other physical and chemical properties were tested.(2)Mice fibroblasts(L929)were inoculated into methacrylated dermal extracellular matrix hydrogel to detect the cell compatibility.(3)Totally 12 SD rats were randomly divided into two groups(n=6)to create abdominal wall defect model with peritoneum preserved.The defect site of the polypropylene group was filled with polypropylene material,and the hydrogel group was filled with methacrylated dermal extracellular matrix hydrogel.The wound skin of both groups was covered with polypropylene material.The wound healing was observed and histological analysis was carried out. RESULTS AND CONCLUSION:(1)Enzymatic hydrolysis had a good decellularization effect on porcine dermis after decellularization,and the original glycosaminoglycans and collagen were well retained.Scanning electron microscope observation revealed that the dermal extracellular matrix hydrogel presented loose and porous structure.The aperture was between 70 and 120 μm.The swelling ratio was(16.88±3.24)%and the water absorption was(94.24±1.11)%.The rheological property test showed that the methacrylated dermal extracellular matrix hydrogel was stable and had shear thinning characteristics,with injectability.(2)CCK-8 assay and live/dead staining showed that methacrylated dermal extracellular matrix hydrogel had good cell compatibility.(3)The results of animal experiments showed that the skin wound healing rate of the experimental group was higher than that of the control group at 7,10,and 14 days after operation(P<0.05).Hematoxylin-eosin and Masson staining of skin and muscle tissue exhibited that compared with the polypropylene group,the skin wound epithelialization,hair follicle formation,collagen fiber arrangement,and neovascularization were better in the hydrogel group 14 days after surgery.The skin wound new tissue structure was similar to the normal tissue at 28 days after surgery,and scar hyperplasia was less.A small amount of muscle regeneration was observed on day 28 after operation.(4)The results show that the methacrylated dermal extracellular matrix hydrogel can promote wound skin healing and muscle tissue regeneration in rats with abdominal wall defect.

Over 2 million thoracoscopic pulmonary resections are performed globally each year,however,postoperative persistent air leak(PAL)remains a common and challenging complication.It not only prolongs hospital stays and increases treatment costs but may also lead to severe complica-tions,particularly inducing a higher risk in patients undergoing mechanical ventilation.In recent years,with the improvement of preoperative preventive measures,the advancement of surgical tech-niques,and the application of repair materials,the incidence of PAL has decreased.This review sys-tematically summarized the definition,clinical impact,risk factors and preventive strategies of PAL,and explored commonly used treatment modalities,such as thoracic drain management,pleurodesis and the application of novel repair materials.It also analyzed the effectiveness,safety and challenges of existing techniques.Furthermore,this review proposed the establishment of an enhanced recovery after surgery(ERAS)integrated pathway combining bovine pericardium(BP)patch with electro-me-chanical stapler and conducted corresponding treatment benefit-cost assessment.

Objective:To evaluate the efficacy of an etoposide (Vp16) -intensified conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of relapsed/refractory acute myeloid leukemia (AML).Method:A retrospective analysis was conducted on the clinical data of 27 recipients with relapsed/refractory AML who underwent allo-HSCT using a Vp16-intensified conditioning regimen at Aerospace Center Hospital from January 2019 to January 2022. Transplantation-related complications and treatment outcomes were observed. Kaplan-Meier survival analysis was used to assess the overall survival (OS) and disease-free survival (DFS) rates.Result:Among the 27 recipients, there were 14 males and 13 females, with a median age of 41 years (range: 12~55 years). Except for one recipient who experienced primary graft failure, the remaining 26 recipients achieved hematopoietic reconstitution. The median neutrophil and platelet engraftment times were 13 days (range: 9~20 days) and 13.5 days (range: 11~33 days), respectively. Regimen-related toxicity (RRT) was mainly gastrointestinal toxicity and oral mucositis, and no deaths were attributed to RRT. A total of 12 recipients (44.44%) developed acute graft-versus-host disease (aGVHD), of whom 3 cases (11.11%) had grade III~IV aGVHD. Chronic GVHD (cGVHD) occurred in 13 recipients (48.15%), including 8 cases (29.63%) of extensive cGVHD. The median follow-up time after transplantation was 17 months (range: 1~48 months). Fifteen recipients (55.56%) survived without disease, while 12 recipients (44.44%) died— 9 due to relapse and 3 due to transplant-related complications. The 1-year overall survival and DFS rates were 74.07% and 59.26%, respectively; the 2-year overall survival and DFS rates were 59.26% and 55.56%, respectively. The 2-year relapse rate and transplant-related mortality (TRM) were 33.33% and 11.11%, respectively.Conclusion:The Vp16-intensified conditioning regimen in allo-HSCT appears to be a viable treatment option for patients with relapsed/refractory AML, offering favorable efficacy and manageable safety.

Objective:To evaluate the efficacy and safety of percutaneous nephrolithotomy (PCNL) in the treatment of severe acute pancreatitis (SAP) with infected pancreatic necrosis (IPN).Methods:A retrospective analysis was conducted on the clinical data of 113 patients with SAP and IPN admitted to Qingdao Municipal Hospital between January 2018 and June 2023. The cohort included 66 males and 47 females, aged (46.2±13.6) years. Based on the treatment approach, patients were divided into two groups: those who underwent percutaneous catheter drainage (PCD) alone were assigned to the PCD group ( n=60), and those who received PCNL were assigned to the PCNL group ( n=53). Clinical parameters such as age, sex, number of debridement procedures, and postoperative complications were recorded. Results:Compared with the PCD group, the PCNL group had a higher CT severity index [8(6, 9) vs. 7(6, 8)], a greater proportion of patients with multiloculated abscesses [71.7%(38/53) vs. 41.7%(25/60)], and a higher percentage of patients with IPN involving >50% necrosis [56.6%(30/53) vs. 33.3%(20/60)]. These differences were statistically significant (all P<0.05). The PCNL group also showed a higher proportion of patients with post-treatment IPN necrosis involving <30% [91.4%(49/53) vs. 70.8%(42/60)], a lower rate of requiring step-up laparoscopic or open surgery [3.8%(2/53) vs. 10.0%(6/60)], fewer debridement sessions [2(1, 4) vs. 4(2, 6)], and a shorter total hospital stay [45(35, 58) d vs. 54(23, 72) d]. These differences were statistically significant (all P<0.05). Additionally, the PCNL group had lower rates of postoperative complications, including enteric fistula [3.8%(2/53) vs. 11.7%(7/60)], intra-abdominal bleeding [5.7%(3/53) vs. 13.3%(8/60)], and pancreatic fistula [15.1%(8/53) vs. 20.0% (12/60)]. These differences were also statistically significant (all P<0.05). The recurrence rate of abscesses was significantly lower in the PCNL group [11.3%(6/53) vs. 16.7%(10/60), χ2=4.14, P=0.042]. Conclusion:PCNL is an effective treatment for SAP complicated by IPN. Compared with PCD, it improves the clearance of necrotic tissue, reduces the number of debridement procedures, shortens the total hospital stay, and lowers the risk of postoperative complications.

BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using"mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice"as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2.(2)Further comparative analyses revealed that miR-216-5p,miR-145-5p,and miR-146b improved inflammatory responses by regulating related pathways.Combining these miRNAs may produce more significant effects;hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy.(3)There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury,which is related to the need to meet good manufacturing practices before they can be put into clinical use.Challenges such as the need for large-scale,high-volume cell production,the lack of an efficient and uniform method for isolating exosomes,and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry.(4)miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury,and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

BACKGROUND:Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway,which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury,and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction.OBJECTIVE:To summarize the role of cellular autophagy in spinal cord injury,related regulatory mechanisms of cellular autophagy and therapeutic strategies.METHODS:PubMed and CNKI databases were searched with the search terms of"spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target"in English and Chinese,respectively.A total of 133 English and 4 Chinese articles were included for review.RESULTS AND CONCLUSION:(1)Autophagy,a form of programmed cell death,has been shown to play a crucial role in the progression and treatment of spinal cord injury.Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis.A few studies have reported that excessive activation of autophagy,on the contrary,impedes neurological recovery following spinal cord injury.(2)After spinal cord injury,PI3K/AKT/mTOR,MAPK,AMPK and p53 signaling pathways,and factors such as Beclin-1,ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner.(3)Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury.And the drugs amlodipine,metformin,and minocycline,the Chinese medicines hawthorn leaf total flavonoids,betulinic acid,oxidized ginseng saponins,acupuncture,and extracellular vesicles of different cellular origins,exosomes and reactive oxygen species-responsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy,while the drugs insulin-like growth factor 1 and eladavone,Chinese medicine ginseng saponin,acupuncture,and hydrogel carrying basic fibroblast growth factor as inhibitors of cellular autophagy promote functional recovery after spinal cord injury by inhibiting excessive cellular autophagy.(4)The related regulators of cellular autophagy are interconnected,and the bi-directional effects of cellular autophagy on spinal cord injury make it necessary to further explore the dominant factors that regulate cellular autophagy.(5)Research on the use of autophagy as a therapeutic target for spinal cord injury is mostly carried out in animal models,but there are no autophagy-related drugs used in the clinical practice,and their safety and efficacy need to be further investigated in the clinical field.