Apolipoprotein B mRNA editing enzyme catalytic polypeptide like 3A(APOBEC3A)mutation is a major driver of cervical cancer.APOBEC3A and human papilloma virus(HPV)is closely related.On the one hand,APOBEC3A can effectively inhibit HPV infection;on the other hand,it can promote the integration of HPV DNA into cervical keratinocytes.This paper reviews the complex interaction between HPV and APOBEC3A,and analyzes the involved viral mechanism and cellular signal pathway.A large number of studies have confirmed that APOBEC3A gene can effectively induce the evolution and development of a variety of malignant tumors,including cervical cancer.However,APOBEC3A protein level is not so high in cancer cells in clinic.This paper also discusses the significance and the potential therapeutic value of APOBEC3A activity in cervical cancer.

Objective To explore the differences in therapeutic efficacy and possible mechanism of different routes of administration of fullerene nanoparticles in the treatment of radiation retinopathy.Methods Eight-week-old adult male SD rats were randomly divided into blank group(Control),irradiation group(X-Ray),irradiation+vitreous cavity administration group[X+F(IVT)],irradiation+ocular surface administration group[X+F(OS)],and irradiation+intravenous administration group[X+F(IV)],with 5 rats in each group.The blank group was not treated,the irradiation groups exposed to X-ray irradiation to establish the model,and fullerenol nanoparticles were given to the treatment groups through different routes after irradiation.At 7,14,and 28 d after modeling,body weight and fundus changes were measured to evaluate drug safety,retinal optical coherence tomography(OCT)was used to observe the change in retinal tissue structure,and electroretinography(ERG)was applied for oscillatory potentials(OPs)to evaluate visual function.CD31 immunofluorescence staining was carried out to evaluate retinal endothelial vascular status,and in vivo imaging was utilized to evaluate the accumulation of fullerenol nanoparticles in the eyes.Results The growth curves of body weight demonstrated that fullerenol nanoparticles did not affect the growth and development of rats,with no statistical difference between the treatment groups and the control group.Irradiation resulted in a significant reduction in visual function,decreased amplitudes of a-wave and b-wave,and declined OPs(P<0.01),and significantly increased thicknesses of the ganglion cell layer(GCL)and the inner nuclear layer(INL)in the retinas,as evidenced by OCT(P<0.01),along with a notably absent presence of CD31-positive cells(P<0.01).Notably,the X+F(IVT)group obtained significantly improved visual function after intravitreal administration,effectively maintained thickness of the GCL and INL,and prevention against the loss of CD31-positive cells(P<0.01).However,no such effective results were observed in the irradiated groups receiving intravenous either ocular surface administration.In vivo imaging revealed that intravitreal administration maintained high ocular accumulation of fullerene for 96 h,while ocular surface administration sustained these concentrations for only 12 h.Intravenous administration,in contrast,only led to a predominant drug distribution in vascular-rich areas,but reduced ocular accumulation.Conclusion Fullerene nanoparticles possess a therapeutic effect on radiation retinopathy,and the intravitreal administration route demonstrates better efficacy than ocular surface and intravenous administration.

Objective To investigate the potential therapeutic targets and underlying molecular mechanisms of Z-ligustilide(Z-LIG)in treating retinitis pigmentosa(RP).Methods By integrating multiple databases,such as GeneCards and TargetNet,common targets for RP and Z-LIG were identified.Protein-protein interaction(PPI)network analysis of the targets was conducted using the STRING database and analyzed in Cytoscape to identify core targets.The DAVID database was employed for the functional enrichment analysis of Gene Ontology(GO)and the pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)for the core targets.The PubChem database was accessed for molecular docking verification to validate the binding affinity between Z-LIG and the core targets.Finally,male rd10 mice were randomly divided into a control group(n=5)and a Z-LIG treatment group(n=5).The protective effect of Z-LIG on the visual function in rd10 mice was verified through visual electrophysiology and behavioral tests.Western blotting and RT-qPCR were utilized to investigate the molecular mechanism of action.Results A total of 66 shared targets between RP and Z-LIG were identified through the screening process.PPI network analysis identified 55 key targets.GO enrichment analysis yielded 623 terms,which covering 3 dimensions,including cellular component(CC),molecular function(MF),and biological process(BP),such as inflammatory response.KEGG pathway enrichment analysis further concentrated 124 terms,which were enriched in the PI3K-Akt signaling pathway.Molecular docking suggested that Z-LIG could specifically bind with high affinity to RP-related core targets(such as EGFR and STAT3)via hydrogen bonds.In animal experiments,compared to the control group,the rd10 mice from the Z-LIG group showed a greater preference for the dark environment in the light/dark transition test(P<0.05),exhibited significantly higher amplitudes of A-wave and B-wave in electroretinogram(ERG)(P<0.05),greater number of outer nuclear layers,with fewer apoptotic cells and less microglial activation(P<0.05),demonstrated obviously reduced protein levels of p-PI3K/PI3K and p-AKT/AKT in the retina(P<0.05),and had notably down-regulated mRNA levels of pro-inflammatory cytokines IL-1β and IL-6(P<0.05).Conclusion Z-LIG may exert a protective effect on the retina of rd10 mice by inhibiting the activation of the PI3K/AKT-inflammatory axis,thereby delaying retinal degeneration.

Objective:To establish a lumbosacral triangle (composed of L 5 transverse process, S 1 superior articular process, sacral ala and iliac crest) classification and to guide L 5S 1 endoscopic surgery. Methods:A total of 647 patients with low back pain who admitted to Tianjin Hospital from January 2016 to October 2018 were retrospectively analyzed, including 315 males and 332 females, aged 42.9±15.1 years (range, 19-74 years). The L 5 transverse process sacral distance (TSD), inter trans-verse process length (ITL), interlaminar width (ILW), interlaminar height (ILH), iliosacral angle (ISA), iliac crest height (IH), intervertebral space height (ISH), intervertebral foramen height (IFH), and intervertebral foramen width (IFW) were measured based on lumbar spine anterior-posterior and lateral radiographs. Spearman correlation analysis and hierarchical cluster analysis were used to establish the lumbosacral triangle classification. A total of 822 patients underwent endoscopic L 5S 1 surgery based on lumbosacral triangle classification guidance and verification in Tianjin Hospital from January 2020 to December 2022, including 421 males and 401 females, aged 45.1±16.7 years (range, 15-79 years). The visual analogue scale (VAS) and Oswestry disability index (ODI) were compared before and after surgery, and the Macnab criteria were used to assess surgical outcomes. Results:Spearman correlation analysis showed positive correlations between IH and ISA ( r=0.75, P<0.001), IFH and IFW ( r=0.60, P<0.001), TSD and IFH ( r=0.53, P<0.001), and TSD and IFW ( r=0.40, P<0.001). There was a negative correlation between TSD and IH ( r=-0.46, P<0.001), TSD and ISA ( r=-0.42, P<0.001), IFW and ISA ( r=-0.41, P<0.001), IFW and IH ( r=-0.50, P<0.001), IFH and IH ( r=-0.42, P<0.001). According to Spearman correlation analysis, hierarchical cluster analysis and receiver operating characteristic curve, lumbosacral angle was divided into three types: Type 1, L5 transverse process overlapped with sacral alar; Type 2, 07 mm. Based on lumbosacral triangle classification, different endoscopic techniques were used at L5S1 in 822 patients, including interlaminar approach single-axis endoscopy, trans-foraminal approach single-axis endoscopy, trans-foraminal fenestration approach mobile microendoscopy and unilateral biportal endoscopy, the VAS and ODI of all the patients decreased than those preoperative in immediate postoperative period, half a year postoperative period and the final follow up, and the difference was statistically significant ( P<0.05). At the last follow-up, the Macnab score was excellent in 278 cases, good in 475 cases, and fair in 69 cases, with an excellent and good rate of 91.6% (753/822). Conclusion:Lumbosacral triangle classification is simple and practical, and can effectively guide L5S1 endoscopic surgery.

Objective:To establish an artificial intelligence-based surgical selection system utilizing deep learning to assist in the decision-making process for lumbar endoscopic surgery.Methods:General data of 1,110 patients who underwent percutaneous transforaminal endoscopic discectomy, 804 patients who underwent percutaneous interlaminar endoscopic discectomy, 923 patients who underwent mobile microendoscopic discectomy and 623 patients who underwent unilateral biportal endoscopic in Tianjin Hospital from January 2018 to June 2023 were included in the study. Clinical outcomes were assessed using the visual analogue scale (VAS) for leg and back pain, the Oswestry disability index (ODI), and MacNab criteria both before surgery and 12 months postoperatively. Using a random number table method, patients were divided into a training dataset (2,768 cases) and a test dataset (692 cases) at a ratio of 4∶1. Patient clinical symptoms, physical signs, and multi-modal imaging data were input into a deep learning model. This model was structured into three main modules: intervertebral disc detection, surgical necessity identification, and surgical recommendation. The final surgical method was determined using a convolutional neural network incorporating U-Net for segmentation and ResNet for classification. The accuracy and recall rates of each module were evaluated using the test dataset.Results:Compared to preoperative values, all patients showed significant improvements at the 12-month postoperative follow-up. For patients who underwent percutaneous transforaminal endoscopic discectomy, percutaneous interlaminar endoscopic discectomy, mobile microendoscopic discectomy, and unilateral biportal endoscopic surgery, the VAS scores for leg pain decreased from 7.69±0.80, 7.82±0.88, 7.62±0.69, and 7.56±1.00 preoperatively to 1.44±1.09, 1.35±0.82, 1.51±1.08, and 1.43±0.91 postoperatively. Similarly, the VAS scores for back pain decreased from 5.73±0.83, 6.17±0.99, 6.11±0.88, and 6.46±0.95 to 0.93±0.75, 1.01±0.67, 1.40±0.72, and 1.27±0.70, respectively. Additionally, the ODI significantly decreased from 39.91%±4.50%, 40.05%±8.05%, 47.08%±9.50%, and 44.43%±4.71% preoperatively to 5.77%±2.22%, 6.05%±2.31%, 8.51%±2.16%, and 9.51%±3.70% postoperatively, with all differences being statistically significant ( P<0.05). The excellent rate according to the MacNab criteria was 93.12% (3,222/3,460). In the deep learning model, the multi-modal data of 2,768 patients were input in the training set for deep learning to form a surgical identification and operation recommendation system, and the preoperative data of 692 patients were input in the test set to compare with the final operation method. In the intervertebral disc location module, the accuracy of location and designation of the five lumbar intervertebral discs was 97.1%(672/692). In the module of intervertebral disc need for surgery, the accuracy was 94.8%(3,280/3,460) and the recall rate was 91.9%(636/692). As for patients, the accuracy rate was 91.9%(636/692). In the operation recommendation module, the accuracy rate of operation recommendation based on intervertebral disc was 89.5%(569/636), and the accuracy rate of surgical recommendation based on patient was 82.2%(569/692). Conclusion:In this study, an artificial intelligent surgical procedures selection system based on deep learning was established, which could effectively integrate relevant data and accurately guide the selection of lumbar endoscopic surgery.

Objective To explore the gene expression profile in paraspinal muscle degeneration(PMD)and identify key ferroptosis genes.Methods RNA sequencing was performed on paraspinal muscle tissue of 3 normal and 3 PMD patients respectively to obtain differentially expressed genes.Through protein-protein interaction(PPI)and gene functional enrichment analysis,the intersection of ferroptosis genes was identified to identify key hub genes associated with ferroptosis.The diagnostic value for PMD disease was analyzed by receiver operating characteristic(ROC)curves.Results A total of 292 differentially expressed genes were identified in PMD.Among them,125 genes were significantly downregulated and 167 genes were significantly upregulated.Bioinformatics analysis revealed that 14 differentially expressed genes were associated with ferroptosis.Among them,ferroptosis genes MUC1,ATF3 and CDKN1A were key hub genes with good specificity and sensitivity for diagnosing PMD.Functional enrichment analysis revealed that they may mediate the occurrence and progression of PMD by regulating cell apoptosis,ferroptosis and skeletal muscle tissue development and differentiation.Conclusion Ferroptosis genes MUC1,ATF3 and CDKN1A can serve as biomarkers for diagnosing PMD,providing theoretical basis for decoding the pathological mechanism of PMD and developing new drugs.

Objective To explore the relationship between phenotypic changes of retinal microglia and retinal ganglion cells(RGCs)death after optic nerve injury.Methods Male C57BL/6J mice(6 to 8 weeks old)were randomly divided into 1-,3-,7-,and 14-day injury groups and sham operation group,with 4 mice in each group.The eyes in the injured groups were inflicted with optic nerve crush(ONC),while the eyes of the sham operation group were treated with the same operation procedure but without optic nerve clamp.Flash visual evoked potential(fVEP)and immunofluorescence staining were employed to evaluate the impact of optic nerve injury on visual function and number of RGCs.RT-qPCR and immunofluorescence staining were applied to detect the effecy of optic nerve injury on phenotypic changes in retinal microglia.Results fVEP results showed that the visual conduction of the injured eye was gradually decreased over time when compared with that of the sham group(P＜0.01).Immunofluorescence staining revealed that the number of RGCs was lost mainly within 7 d after injury(P＜0.01).At the same time,the number of retinal microglia reached its peak at 7 d after injury(P＜0.01).RT-qPCR indicated that the expression of disease-associated microglia(DAM)and interferon-responsive microglia(IRM)specific genes were significantly increased when compared with the sham group at 7 d after ONC(P＜0.01).Immunofluorescence staining displayed that the number of DAM peaked at 3 d after ONC(P＜0.01),but the proportion was decreased gradually with the progress of time(P＜0.05).The number and proportion of IRM peaked 7 d after ONC(P＜0.01).Correlation analysis suggested that the number of IRM was strongly correlated with the loss of ganglion cells(P＜0.01).Conclusion The conversion of retinal microglia from DAM type to IRM type after optic nerve injury may be an important cause of ganglion cell loss.

Objective:To investigate the effect of unilateral biportal endoscopy (UBE) through extraforaminal approach in the treatment of extra canal lumbosacral nerve entrapment.Methods:Seventeen patients with extra canal lumbosacral nerve root entrapment were treated by UBE through extraforaminal approach in Tianjin Hospital from January 2020 to March 2022, including 9 males and 8 females with an average age of 59.2 years (range 45-71 years). All 17 patients had lower limb radiation pain, numbness, and weakness with or without intermittent claudication. MRI imaging examination showed L 4, 5 foramen stenosis with far lateral disc herniation in 2 case, and L 5S 1 foramen stenosis with far lateral disc herniation in 15 cases, and the height of intervertebral space decreased, resulting in the compression of exiting nerve root and ganglion. Among them, far-out syndrome was diagnosed in 7 cases and transitional lumbarsacral vertebrae was found in 12 cases. The incisions were designed 2 cm away form the projection of adjacent pedicles, while incision at S 1 was designed at the inner edge of the iliac bone due to the shielding of the ilium, taking the outer edge of the isthmus at the outer opening of the intervertebral foramen as the target of channels. The ventral and apical part of superior articular process (SAP) was gradually removed with high-speed burr from its outer edge and isthmus, and the occluded sacral ala and the lower edge of transverse process were removed when necessary. The hyperplastic ligament was removed to expose the exiting nerve root. The protruding intervertebral disc was removed at the ventral side of the nerve root. The far-out syndrome was decompressed laterally along the exiting nerve root until it is completely released. The results and stability were evaluated with visual analogue scale (VAS), Oswestry disability index (ODI), Macnab scores and dynamic X-ray film during follow-up. Results:The operation time was 45-85 min, with an average of 60 min. After remove of the SAP tip and enlarge of the intervertebral foramen, the exiting nerve root and disc protrusion were fully exposed, the exiting nerve root was exposed and released laterally until totally release without entrapment in far out syndrome, and the nerve could be decompressed completely. The symptoms were significantly relieved after operation, and imaging examination showed that facet joints were preserved. During follow-up, the pain and function improved continuously. At final follow-up, the improve rate of VAS and ODI were 85.2% and 86.2%, respectively, and the results were excellent in 15 cases and good in 2 case according to Macnab score, and there was no lumbar instability on dynamic lumbar X-ray film.Conclusion:Extra canal lumbosacral nerve entrapment can be treated by UBE through extraforaminal approach, with sufficient exposure, complete decompression and better preservation of lumbar stability.

Intervertebral disc degeneration is the most common cause of chronic low back pain and the leading cause of disability in adults. The fact that lacking of effective treatment methods often causes a serious economic and social burden. Intervertebral disc degeneration is the result of multifactorial factors. The prevalence of intervertebral disc degeneration increases drastically with age, what is more, mechanical trauma, genetic predisposition,lifestyle factors and certain metabolic disorders. At present, the main treatment methods both pharmacological and surgical interventions just aim at relieving symptoms and improving function, and can not fundamentally reverse the process of intervertebral disc degeneration, which not only bring inevitable side effects and high cost, but also the long-term curative effect is limited. In theory, biological therapy can not only reverse or delay the process of it, but also can maximize preservation and restore the normal physiological function of the disc, which has been the focus and hot spot areas of research in recent years. The methods of inhibiting inflammation, promote the proliferation and division of residual cells, stem cell transplantation, cell scaffolds and new biomaterials all provide new ideas and direction for the treatment of intervertebral disc degeneration. This paper makes a review of the research progress in related fields, in order to provide a valuable reference for the selection of intervertebral disc degeneration treatment options.

Objective:To investigate the effect of Ponte osteotomy combined with bony bridge dissection and intervertebral bone grafting in the treatment of rigid degenerative scoliosis.Methods:From March 2017 to October 2021, this method was used to treat 21 cases of rigid degenerative scoliosis, including 7 males and 14 females, aged 59-76 years, with an average age of 67.6 years. All patients had intractable low back pain and limited standing and walking, while 15 patients had radiation pain in lower limbs. The preoperative standing X-ray film showed that the average Cobb angle of lumbar scoliosis was 51.3°±24.1°, the average lumbar lordosis was 5.4°±13.6°. The coronal balance distance (CBD) was 4.3±2.0 cm (range, 0.5-6.2 cm), and the sagittal vertical axis (SVA) was 5.9±3.1 cm (range, 1.5-6.8 cm). The bending images showed huge osteophyte with bone bridge formation in the vertebral body of the apex region, with poor mobility. Ponte osteotomy was performed according to the degeneration of the deformity. The bone bridge at apex area was cut off, and the intervertebral spaces at apex area and slipped or subluxated levels were release and grafted with granular autogenous decompression bone. During follow-up, the efficacy and deformity improvement were evaluated with visual analogue scale (VAS), Oswestry disability index (ODI) and standing X-ray films.Results:All patients successfully completed the operation. The operation time was 190-330 min, with an average of 250±68 min. The intraoperative bleeding was 700-1600 ml, with an average of 970±260ml. The patients were followed up for 12-36 months, with an average of 20.6±7.2 months. No internal fixation failure, fracture or revision occurred. At the last follow-up, the VAS of low back pain decreased from preoperative 6.1±2.2 to 2.1±1.8 ( t=6.45, P<0.001), and the leg pain decreased from 5.5±3.4 to 1.2±1.0 ( t=5.56, P<0.001).ODI decreased from 52.2%±22.2% to 16.4%±10.6% ( t=6.67, P<0.001). The Cobb angle of lumbar scoliosis was 19.3°±10.5°, with an average correction rate of 62.4%; lumbar lordosis was 34.4°±15.6 °, with average correction of 30°. CBD was 1.9±1.1 cm, with an average correction of 2.4 cm ( t=4.42, P<0.001); and SVA was 1.6±2.1 cm, with an average correction of 4.3 cm ( t=4.90, P<0.001). Conclusion:Ponte osteotomy combined with bone bridge dissection and intervertebral bone grafting is an effective method to treat rigid degenerative scoliosis, which can improve spinal sequence, CBD and SVA, avoid vertebral osteotomy and reduce fusion segments.