Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

Objective To investigate the inhibitory effects of pyruvate-ferredoxin oxidoreductase(PFOR)by luteolin and its anti-Clostridium difficile effect.Methods The PFOR encoding sequence of Clostridium difficile was cloned into the expression vector pET-2a and transformed into competent Escherichia coli.The crude enzyme was prepared after induction with IPTG(Isopropyl β-D-Thiogalactoside).The inhibitory rate of the test compounds on PFOR was determined after an 8-hour anaerobic reaction between PFOR and 40 μmol·L-1 of test compounds at 25℃.The minimum inhibitory concentration(MIC)of PFOR inhibitors against C.difficile strains(ATCC BAA 1382 and ATCC BAA 1870)was determined by monitoring the OD600 of the bacterial culture.Molecular docking was performed to investigate the possible interaction mechanisms between PFOR and inhibitors.Results Among the tested compounds,the luteolin showed the strongest inhibitory activity against PFOR,with a single-point inhibition rate of approximately 33%,which is comparable to that observed with the positive inhibitor nitazoxanide(40%).Molecular docking revealed that luteolin could form hydrogen bonds with Asp428,Val431,Gly429,Asp456,Lys458,Lys459,and other residues in the PFOR domain.The MIC of luteolin against C.difficile was approximately 32 μg·mL-1.Conclusion Luteolin exhibits good activity against C.difficile,and PFOR may be a target for its antibacterial action.

Objective Ionization chamber detector is commonly used for direct and continuous measurement of tritium concentration in the air. However, the measurement sensitivity is low due to the limitations of weak current measurement technology. It is necessary to develop a proportional counter for measuring tritium in the air. Methods This study involved the design of a proportional counter, considering various factors such as materials and structure. The stability, plateau curve, detection efficiency, and energy spectrum of the counter were tested. Results The coefficient of variation of the proportional counter was 3.14%, which met the standard requirement of being less than 15%. The plateau length was 260 V and the plateau slope was 0.80%/100V, which met the requirement of being less than 1%/100V. The tritium detection efficiency reached 68.02%. The energy spectrum measurement indicated a significant difference between tritium signal generated by the proportional counter and background signal, and the distribution of tritium in the energy spectrum was more concentrated. The background counting rate during tritium gas activity measurement could be reduced through energy spectrum measurement. Conclusion The proportional counter can provide a reference for the direct and continuous measurement of tritium in the air.

OBJECTIVE To investigate the activation of xanthine oxidase(XO)from the human liver by vitamin K3 and the mechanism.METHODS Using human liver S9(0.1 g·L-1)as the source,XO was incubated with substrate xanthine of 0,2,4,8,and 16 μmol·L-1 at 37℃ for 90 min.The Michaelis constant(Km)of the reaction of xanthine oxidation was determined using the liquid chromatography diode array method.At the concentration of Km,the three-point method(1,10 and 100 μmol·L-1)was used to detect the activity of vitamin K3 activators.The multi-point method(vitamin K3 1,2,5,10,20,50,100,200 and 400 μmol·L-1)was adopted to determine the half effective concentration(EC50)of activated XO.Kinetic parameters(Km and Vmax)and the fit of double reciprocal curves were determined via vitamin K3 of 1/2EC50,EC50 and 2EC50.The changes in kinetic behavior at different concentrations of vitamin K3 were observed and their types of activation were analyzed.The interactions between XO and activator vitamin K3 were explored via molecular docking.RESULTS The Km of XO-mediated xanthine oxidation reac-tion was 4.71 μmol·L-1.As an activator of this reaction,vitamin K3 activated XO in a concentration-dependent manner(according to the logistic fitting formula y=A2+(A1-A2)/(1+(x/x0)^p),with an EC50 of 32.0 μmol·L-1.The kinetic parameters also changed after the addition of vitamin K3.The Km value decreased(4.71-1.34 μmol·L-1)with the increase of vitamin K3 concentrations,while the Vmax value increased(0.08-1.31 μmol·min-1·g-1),leading to an increase in Vmax/Km(17.0-977.6 mL·min·g-1).In addition,the double reciprocal curve fitting found that the activation type of vitamin K3 on XO was mixed.The molecular docking results showed that vitamin K3 bound to the molybdopterin domain of XO and maintained hydrogen bonding interactions with Arg599 and Ser605.CONCLUSION Vitamin K3 is an activator of XO,which can form hydrogen bonds with Arg599 and Ser605 in the XO domain,regu-late its affinity with the substrate xanthine,activate XO and increase the uric acid level.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

BACKGROUND:Ligaments are important structures in maintaining the stability of the lumbar spine,and these structures are prone to degradation due to the generated mechanical stress.However,there are few studies on ligament injuries. OBJECTIVE:To determine the range of motion and stress of each ligament in the state of motion based on a three-dimensional finite element model,and to systematically explore the influence of ligament injury on the stability of the lumbar spine and its biomechanical significance. METHODS:The L4-L5 lumbar finite element model was established.All free forces on the lower surface of L5 were constrained,and a torque of 5 N·m was applied to simulate the motion states of the lumbar spine.Progressive ligament damage was simulated by changing Young's modulus of the ligament. RESULTS AND CONCLUSION:(1)The extension range of motion of most ligament injuries increased significantly.In contrast,there was no significant change in the lateral bending range of motion.(2)The range of motion of capsular ligament injury increased significantly in flexion,extension and lateral bending.The extension range of motion increased significantly after the anterior longitudinal ligament injury.Intertransverse ligament injury resulted in a significant increase in the lateral bending range of motion.(3)After a single ligament injury,the most significant change in range of motion was observed during extension.After a single ligament injury,the stress of the remaining ligaments increased,especially the capsular ligament.The stress changes of the interspinous ligament and ligamentum flavum were the least obvious.Ligament stress changes least in lateral bending and most in torsion.(4)Ligament damage did not result in major changes in disc pressure,indicating that ligament injury leads to an increased range of motion of the lumbar spine and affects the stability of the lumbar spine.(5)Capsular ligament was stable in flexion,extension and lateral bending.The anterior longitudinal ligament showed a stable extension;the intertransverse ligament stabilizes the lateral curve.(6)Extension exercise is sensitive to a ligament injury,and the pathological changes of the ligament can be examined by extension exercise.(7)Stress compensation was given to the remaining ligaments to maintain the stability of the lumbar spine after a single ligament injury.(8)Interspinous ligament and ligamentum flavum injuries have the least impact on the peripheral ligaments,while capsular ligament injuries have the greatest impact on the peripheral ligaments.(9)The ligament injury has the least effect on the residual ligament stress during lateral bending exercise,while it has the greatest effect on the ligament stress during the twisting exercise.Patients with ligament injury should avoid twisting exercises.Ligament injuries do not affect disc pressure.

BACKGROUND:Establishing an objective and standard animal model of bone nonunion is essential for experimental studies and treatment of nonunion. OBJECTIVE:To establish an objective animal model for experimental studies of nonunion. METHODS:Specific pathogen-free male Wistar rats were selected and prepared by cutting off a 5 mm bone defect in the middle femur,peeling off a large periosteum and removing bone marrow.Animal models were fixed with a 1.2 mm Kirschner wire.At 1,4 and 8 weeks,bone nonunion was observed by gross specimen observation,X-ray examination and histopathological examination. RESULTS AND CONCLUSION:The gross specimen,X-ray film and histopathological examination showed that there was no callus formation in the bone defect area,the broken end was filled with fiber tissue,and the bone callus was rare or even invisible.To conclude,the rat model of nonunion can be successfully established by osteotomy of the middle femur,large periosteum peeling and bone marrow removal.This modeling method is simple,reliable and effective.

BACKGROUND:Ligaments are an important structure for stabilizing the lumbar spine,and they are prone to degenerative changes with age.Currently,there is limited research on lumbar ligaments. OBJECTIVE:To investigate the effect of different combinations of ligament injuries on biomechanical characteristics of lumbar spine under four motion states of forward bending,backward extension,lateral bending,and torsion under a certain sequence of ligament injuries. METHODS:A finite element model of the L4-L5 segment of the lumbar spine was established,and corresponding moments were applied to simulate four motion states of forward bending,backward extension,lateral bending,and torsion.The combined injuries of the ligaments were performed in order to obtain the motion range of each vertebra and the stress of each ligament. RESULTS AND CONCLUSION:(1)Every time a ligament was removed,the remaining ligament stress would increase.Under all four working conditions,capsular ligament would experience the highest stress,especially during forward bending.With the removal of ligaments,the range of motion of the vertebrae was also continuously increasing.(2)When flexing forward,after removing the first ligament capsular ligament,the average stress change in the remaining ligament was the highest,followed by the removal of supraspinous ligament.After removing capsular ligament,the change rate of range of motion was the highest,while after removing posterior longitudinal ligament,the change rate of range of motion was the lowest.(3)When extending backward,all ligaments had the highest rate of stress change after removing capsular ligament,the highest rate of range of motion change after removing capsular ligament,and the lowest rate of range of motion change after removing posterior longitudinal ligament.(4)When bending,the stress change rate of interspinous ligament decreased after removing intertransverse ligament,while supraspinous ligament increased more.After removing capsular ligament and interspinous ligament,the range of motion change rate increased significantly.(5)During lateral bending,after removing capsular ligament,the stress change rate of the remaining ligament was much higher than that of other ligament damage combinations,and the range of motion change rate was the highest after removing capsular ligament.In other cases,the range of motion change rate did not exceed 8%.(6)If the root ligament is damaged,the remaining ligaments will undergo stress compensation.Ligament damage will affect the stability of the lumbar spine,with minimal impact in cases of lateral curvature.Patients with lumbar instability should avoid forward flexion and backward extension movements,which can make it easier to detect the pathological condition of the ligaments.(7)Capsular ligament is an important structure for maintaining lumbar stability,and supraspinous ligament plays a significant role in anterior flexion,maintaining the integrity of the entire lumbar ligament.

Objective:To elucidate the quasispecies variation of 3′ half-length genome in HIV-1 CRF103_01B-infected patients in Beijing using single genome amplification (SGA).Methods:This study enrolled six CRF103_01B-infected patients who were diagnosed during a drug resistance monitoring for newly diagnosed cases or newly treated cases with antiviral therapy in Beijing from 2017 to 2020. RNA was extracted from their plasma samples, and 3′ end of cDNA was diluted by serial dilution method after reverse transcription. Nested PCR was used to amplify the 3′ half-length genome sequences of HIV-1 quasispecies. MEGA 11 was used to construct Neighbor-Joining (NJ) tree and calculate the intrahost genetic distance. Genetic variation in HIV-1 quasispecies was visualized by online Highlighter tool. BootScan analysis was performed using Simplot 3.5 software to analyze inter-quasispecies recombination. Virus tropism was predicted by online Geno2pheno tool.Results:Among the six CRF103_01B-infected patients, five were men who have sex with men. A total of 144 3′ half-length genome SGA sequences (19-36 sequences/case) were obtained. The NJ tree based on the 3′ half-length genome of HIV-1 quasispecies revealed different degrees of genetic diversity. The HIV-1 quasispecies in BL4748-00 case of acute infection has the least variation with the intrahost distance of 0.002±0.000, showing genetic homogeneity. The quasispecies sequences from BL4981-00, BL3150-00 and BL3558-00 cases formed at least three subclusters, respectively, with different evolutionary directions, and their intrahost distance ranked from 0.031±0.004 to 0.016±0.002 (BL3150-00>BL3558-00>BL4981-00). The quasispecies sequences from the couple BL3022-00 (female) and BL3023-00 clustered into a large monophyletic cluster (bootstrap value=100%), and the intrahost distance of the latter (0.025±0.003) was higher than that of the former (0.019±0.002). Inter-quasispecies recombination was observed in BL3558-00 case. The quasispecies from the six patients were CCR5-tropic viruses.Conclusions:The diversity of quasispecies variation in CRF103_01B-infected patients is related to disease progress. Genetic homogeneity is observed in acute HIV infection, while multiple evolutionary directions are detected in chronic infection. Co-infection or superinfection cases are not found, but there are recombination events among quasispecies in some cases.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.