BACKGROUND:In 2019,the modified cortical bone trajectory technique was proposed by our team,significantly improving traditional methods.Previous studies have highlighted its superior biomechanical properties for segment fixation.However,a comprehensive systematic analysis of its specific biomechanical effects on adjacent segment degeneration is lacking,particularly regarding its influence on range of motion and intervertebral disc stress in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion techniques.OBJECTIVE:To investigate the biomechanical effects of modified cortical bone trajectory screw techniques on adjacent segment degeneration in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion.METHODS:CT scans were performed on three human cadaver specimens to establish and validate three-dimensional intact finite element models of the L1-S1 segment.For each of these,the posterior lumbar interbody fusion or transforaminal lumbar interbody fusion with three different fixation techniques was reconstructed at the L4-L5 segment.The L4-L5 segment was fixed using three different internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws).The range of motion and von Mises stress of the intervertebral disc of the L3-L4 and L5-S1 segments were recorded with a 400 N compressive load and 7.5 N moments in flexion,extension,left-right bending,and left-right rotation.The impacts of the three internal fixation techniques on adjacent segment degeneration in the two kinds of fusion were compared and analyzed.RESULTS AND CONCLUSION:(1)In the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw group showed a reduced range of motion on adjacent segments(L3-L4,L5-S1)under six loading conditions compared to both the cortical bone trajectory screw group and traditional bone trajectory screw group.Specifically,the modified cortical bone trajectory screw group significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared to the traditional bone trajectory screw group(P=0.005),while the stress on the intervertebral disc in the inferior adjacent segment(L5-S1)exhibited greater dispersion.Similarly,the cortical bone trajectory screw group also significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared with the traditional bone trajectory screw group(P=0.03).(2)Compared with transforaminal lumbar interbody fusion,the three internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws)showed a trend of reduced range of motion in the inferior adjacent segment(L5-S1)under six loading conditions.In contrast,the maximum stress on the intervertebral discs in both the superior and inferior adjacent segments(L3-L4,L5-S1)exhibited an increasing trend in the posterior lumbar interbody fusion model.(3)It is concluded that in the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw exhibited superior biomechanical properties in reducing the range of motion at adjacent segments,which may have a beneficial effect on reducing the risk of adjacent segment degeneration.

BACKGROUND:In 2019,the modified cortical bone trajectory technique was proposed by our team,significantly improving traditional methods.Previous studies have highlighted its superior biomechanical properties for segment fixation.However,a comprehensive systematic analysis of its specific biomechanical effects on adjacent segment degeneration is lacking,particularly regarding its influence on range of motion and intervertebral disc stress in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion techniques.OBJECTIVE:To investigate the biomechanical effects of modified cortical bone trajectory screw techniques on adjacent segment degeneration in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion.METHODS:CT scans were performed on three human cadaver specimens to establish and validate three-dimensional intact finite element models of the L1-S1 segment.For each of these,the posterior lumbar interbody fusion or transforaminal lumbar interbody fusion with three different fixation techniques was reconstructed at the L4-L5 segment.The L4-L5 segment was fixed using three different internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws).The range of motion and von Mises stress of the intervertebral disc of the L3-L4 and L5-S1 segments were recorded with a 400 N compressive load and 7.5 N moments in flexion,extension,left-right bending,and left-right rotation.The impacts of the three internal fixation techniques on adjacent segment degeneration in the two kinds of fusion were compared and analyzed.RESULTS AND CONCLUSION:(1)In the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw group showed a reduced range of motion on adjacent segments(L3-L4,L5-S1)under six loading conditions compared to both the cortical bone trajectory screw group and traditional bone trajectory screw group.Specifically,the modified cortical bone trajectory screw group significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared to the traditional bone trajectory screw group(P=0.005),while the stress on the intervertebral disc in the inferior adjacent segment(L5-S1)exhibited greater dispersion.Similarly,the cortical bone trajectory screw group also significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared with the traditional bone trajectory screw group(P=0.03).(2)Compared with transforaminal lumbar interbody fusion,the three internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws)showed a trend of reduced range of motion in the inferior adjacent segment(L5-S1)under six loading conditions.In contrast,the maximum stress on the intervertebral discs in both the superior and inferior adjacent segments(L3-L4,L5-S1)exhibited an increasing trend in the posterior lumbar interbody fusion model.(3)It is concluded that in the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw exhibited superior biomechanical properties in reducing the range of motion at adjacent segments,which may have a beneficial effect on reducing the risk of adjacent segment degeneration.

To investigate the detection status of human papillomavirus (HPV) among adult women in high-altitude regions of Xizang.

Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

AIM:To examine the impact of the transcription factor 7 analogue 2(TCF7L2)gene polymorphism on the hypoglycaemic effect of ex-enatide in patients with type 2 diabetes mellitus(T2DM).METHODS:A total of 100 newly diagnosed Han Chinese patients with T2DM who had not re-ceived any drug treatment were selected from the Affiliated Hospital of Xuzhou Medical University and treated with exenatide monotherapy for 6 months.The TCF7L2 rs290487 was genotyped by SnaPshot method,and blood glucose levels,lipids profiles and pancreatic function evaluation indica-tors were measured at baseline,3 months and 6 months after exenatide treatment.Multiple linear regression analysis was employed to assess the cor-relation between each indicator and the reduction in glycated hemoglobin(HbA1c)levels after 6 months of exenatide treatment.The expression of TCF7L2 protein in the plasma of T2DM patients was detected by enzyme-linked immunosorbent assay(ELISA)kit.Furthermore,western blotting was con-ducted to ascertain TCF7L2 expression in pancreat-ic tissues obtained from db/db mice and INS-1 cells cultured under high glucose conditions.Lentivirus transfection was used to overexpress or knock down TCF7L2 in insulinoma cell line(INS-1)cells,followed by measurement of KSIS activity and insu-lin content after a 24-hour intervention with exena-tide.RESULTS:The distribution pattern of TCF7L2 rs290487 was found to be in accordance with Har-dy-Weinberg equilibrium(P＞0.05).Following 6 months of exenatide treatment,there was a nota-ble reduction in blood glucose levels and an im-provement in lipid profiles when compared to base-line values.Additionally,there was a significant in-crease in the homeostasis model assessment of be-ta-cell function(HOMA-B)values.Patients with the TT genotype exhibited significantly lower postpran-dial plasma glucose(PPG)levels and HbA1c values compared to those with the CC or CT genotypes(P＜0.05).After adjusting for age,gender,body mass in-dex(BMI),and waist to hip ratio(WHR)in the mul-tiple linear regression model,a significant associa-tion was observed between the rs290487 TT geno-type,baseline HbA1c levels,and family history of diabetes with the reduction in HbA1c after six months of exenatide treatment(P＜0.05).Further-more,individuals with the rs290487 TT genotype demonstrated a notable elevation in TCF7L2 expres-sion in plasma among T2DM patients in comparison to those with the CC genotype(P＜0.05).In particu-lar,pancreatic tissue from db/db mice exhibited markedly elevated TCF7L2 expression compared to db/m mice.However,this up-regulation was re-versed by exenatide treatment.Similarly,INS-1 cells cultured under high glucose conditions dem-onstrated an increase in TCF7L2 expression,which was ameliorated upon exenatide administration.The knockdown of TCF7L2 using shRNA enhanced the KSIS function of pancreatic β cells and aug-mented the insulinotropic effect of exenatide.Con-versely,the upregulation of TCF7L2 impaired the KSIS function of pancreatic β cells and attenuated the insulinotropic effect of exenatide.CONCLU-SION:The TCF7L2 rs290487 gene polymorphism is closely associated with the hypoglycaemic efficacy of exenatide therapy.The risk allele C may diminish the effectiveness of exenatide by impacting the lev-els of PPG and HbA1c in T2DM patients.The muta-tion at TCF7L2 rs290487 site(C→T)influenced the expression of TCF7L2 protein.By exerting its regula-tory effect,exenatide may be capable of regulating the impact of TCF7L2 on the function of pancreaticβ cells.

The frequent challenges encountered in spinal surgeries utilizing pedicle screws for osteoporotic patients include inadequate fixation strength and postoperative screw loosening or displacement, often requiring reinforcement or surgical revision. The bone cement-augmented technique, without altering the diameter, length, or material of the screws, can solidly enhance the stability of internal fixation and improve surgical efficacy. The bone cement types that are widely applied in clinical practice encompass Polymethyl Methacrylate (PMMA), Calcium Phosphate Cement (CPC), and their composite series.The bone cement reinforcement techniques are mainly divided into two categories: bone cement augmentation within pedicle screw pathway and hollow lateral-hole screw reinforcement. The technique of pedicle screw pathway bone cement augmentation significantly enhances the stability of internal fixation by pre-injecting bone cement into the pedicle screw pathway before inserting the screw. However, it poses potential risks such as difficulty in precisely controlling the distribution of bone cement and susceptibility to leakage. In comparison, hollow lateral-hole screw augmentation, through the optimization of bone cement injection techniques and screw design, not only augments screw stability but also effectively decreases the incidence of complications such as bone cement leakage, especially exhibiting outstanding performance in both primary and revision surgeries. For patients with severe osteoporosis or those requiring revision surgery due to compromised pedicle screw tracts, the bone cement-augmented cortical bone trajectory (CBT) exhibits favorable mechanical properties. By adjusting the screw placement pathway, it may potentially avoid the central venous sinus of the vertebra, thereby reducing the risk of bone cement leakage and embolism. However, further research is needed to confirm these findings. With the rapid development of robot-assisted pedicle screw placement technology, the precision and safety of spinal screws augmented with bone cement have been significantly enhanced, effectively minimizing surgical trauma and reducing the risk of complications. In the future, clinicians will make more scientific and objective selections of appropriate screw types and method of screw placement based on patients' bone quality, further reducing complications and adhering to the principle of personalized treatment. This will continuously enhance patient outcomes and prognosis, ultimately providing safer and more effective treatment options for patients.

Objective To construct a predictive model for clinical pregnancy outcomes in frozen-thawed embryo transfer(FET)cycles in women with advanced maternal age(age≥35 years)and to analyze its influencing factors.Methods A retrospective analysis was conducted on the clinical data of 2717 older patients who underwent FET treatment at the First Affiliated Hospital of Kunming Medical University from January 2018 to December 2023.These Patients were divided into a clinical pregnancy group(n=851)and a non-clinical pregnancy group(n=1866)based on whether the clinical pregnancy had occurred.The general characteristics and transplantation details of the two groups were compared,and a logistic regression analysis model was constructed.Results The clinical pregnancy rate(CPR)was 31.32%.The CPR for women aged 35-40 years(40.06%)was higher than that for women aged≥40 years(19.35%),with a statistically significant difference(χ2=133.371,P<0.05).The model results showed that the higher anti-Mullerian hormone(AMH)levels(OR=1.053,95%CI:1.012-1.095),the more high-quality blastocysts were transferred(OR=1.704,95%CI:1.143-2.542;OR=2.861,95%CI:1.921-4.262);the more high-quality blastocysts were transferred(OR=2.033,95%CI:1.077-3.836;OR=3.886,95%CI:2.035-7.420),the thicker the endometrial lining on the day of transfer(OR=1.150,95%CI:1.092-1.212)and it could increase the probability of clinical pregnancy.However,for women over 40 years of age(OR=0.551,95%CI:0.437-0.694)and secondary infertility(OR=0.704,95%CI:0.552-0.896),the probability of clinical pregnancy would be reduced;ROC curve analysis results showed that the AUC for predicting clinical pregnancy occurrence in the training set and validation set of the predictive model were 0.723(95%CI:0.699-0.748)and 0.726(95%CI:0.689-0.764),respectively,with cutoff values of 0.262 and 0.260 and the model fit was good(P>0.05).Conclusion Female age,AMH level,type of infertility,number of high-quality embryos(cleavage embryos,blastocysts)transferred,and endometrial thickness on the day of transfer are important factors affecting FET cycles in advanced maternal age women.The constructed prediction model based on these factors has a certain predictive ability for clinical pregnancy.

BACKGROUND:Osteoporotic trabecular structures are insufficient to maintain screw holding force,often leading to spinal fixation failure.Currently,the following four aspects are mainly used to solve this problem:(1)screw material;(2)surface coating treatment;(3)screw channel solidification strategy;(4)screw shape.The screw channel of the modified cortical bone trajectory screw placement technique has been proven to have a good fixation effect,but there is an urgent need to develop matching screws.OBJECTIVE:To compare the biomechanical performance differences of various types of spinal cortical bone thread screws in the modified cortical bone trajectory fixation of lumbar vertebrae using the finite element method.METHODS:The L4 vertebral models were constructed based on the CT data of three adult wet lumbar specimens(two males and one female)and subjected to finite element analysis.In the modified cortical bone trajectory fixation technique,fully cortical bone thread screws(single thread screws)with lengths of 45 mm and diameters of 5.5 mm and 4.5 mm were used and considered as groups A and B,which were compared with those of the traditional pedicle screw technique group(group C,6.0 mm diameter,45 mm length,double-threaded screw)and the cortical bone trajectory screw group(group D,4.5 mm diameter,45 mm length,double-threaded screw).Axial pull-out force,screw stability(determined by the displacement ratio of upper,lower,left,and right loads),and anti-spin-out torque were measured to compare fixation strength of each group of screws.RESULTS AND CONCLUSION:(1)Axial pull-out force:Group A＞group B(P=0.003),and both group A and group B were greater than the group C(P＜0.001,P=0.003)and group D(all P＜0.001).(2)Screw stability:When load was applied in the upward and downward directions on the screw,the load displacement ratio of the four screw double threads was greater in group A than in group B(P＞0.05);both group A and group B were greater than the group C(all P＜0.001)and the group D(all P＜0.001).(3)Anti-spin-out torque:Group A＞group B(P=0.008),and both group A and group B were greater than the group C(P=0.008,P=0.131).(4)It is indicated that during modified cortical bone trajectory fixation of lumbar vertebrae,the novel spinal cortical bone thread screw demonstrates superior biomechanical performance compared to double thread screws applied in the clinically classic pedicle screw trajectory and cortical bone trajectory.Additionally,the novel spinal cortical bone thread screw(D=5.5 mm,L=45 mm)becomes the optimal adaptation for the modified cortical bone trajectory screw path.

Objective Exploring the clinical diagnosis and treatment status of epilepsy patients at the epilepsy specialty clinic in a single-center comprehensive hospital in the Lhasa area of the Tibetan Plateau.Methods Epilepsy patients who visited the epilepsy specialty clinic of the Department of Neurology at the Tibet Autonomous Region People's Hospital from September 2021 to June 2023 were continuously enrolled.Data such as clinical characteristics and diagnosis and treatment conditions of the enrolled patients was analyzed.Results A total of 121 patients were enrolled in this study,with 33.9%(41/121 cases)being new patients at our hospital and 6.6%(8/121 cases)being referred to our hospital.Non-adherence to treatment,with patients self-reducing or stopping medication without medical advice,accounted for 8.3%(10/121 cases)of the cases.The majority of epilepsy patients were in the young and middle-aged group,with 51.2%(62/121 cases)being between 18 and 44 years old.There were significant differences in the distribution of epilepsy patients across different age groups(P<0.001),while there was no significant difference in gender distribution(49.6%male vs.50.4%female,P>0.05).Generalized seizures were the predominant type of seizure(75.2%,91/121 cases),and 73.6%(89/121 cases)of the patients had an unknown etiology for their epilepsy,with symptomatic epilepsy accounting for 26.4%(32/121 cases)and structural causes being the most common at 24.8%(30/121 cases).Monotherapy was the main treatment for epilepsy(55.4%,67/121 cases),with sodium valproate being the most frequently prescribed drug for monotherapy at 22.3%(27/121 cases).Conclusion In the epilepsy specialty clinic in the plateau region,newly diagnosed patients account for about one-third,and over one-tenth of revisiting patients have not been receiving standardized treatment.The majority of our epilepsy patients are young to middle-aged adults.Generalized seizures are the predominant type.The etiology is unknown in the majority of cases,with structural causes being a common etiology in symptomatic epilepsy.Sodium valproate is the most frequently used antiseizure medication(ASM)in monotherapy in the plateau area.

Objective:To investigate the effect of DEAD-box helicase (DDX) 21 on myocardial ischemia-reperfusion (I/R) injury and its potential mechanisms.Methods:In vivo, adult male Bama pigs and C57BL/6J mice were used to establish a myocardial I/R injury model by ligating the left anterior descending coronary artery, with sham-operated groups set as controls. The expression of DDX21 in myocardium after I/R injury was assessed by quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence staining. Following the establishment of the myocardial I/R injury model in mice, AAV9 vectors with cardiac-specific expression were injected in situ into the peri-infarct region (The I/R+DDX21 group, I/R+negative control (NC) group, I/R+sh-NC group and I/R+sh-DDX21 group were injected with AAV9:cTnT-DDX21, AAV9:cTnT-NC, AAV9:cTnT-sh-NC and AAV9:cTnT-sh-DDX21, respectively). Additionally, the I/R+A-485 group received intraperitoneal injections of the cAMP response element-binding protein (CREB) binding protein inhibitor A-485, while the I/R+PBS group was injected with an equivalent volume of phosphate-buffered saline (PBS) as the control. Echocardiography was performed on postoperative days 1 and 28 to evaluate cardiac function (left ventricular ejection fraction and fractional shortening). At 28 days post-surgery, mice were euthanized and heart tissues were harvested for histological sectioning. Myocardial fibrosis was evaluated using Masson′s trichrome staining. In vitro, primary cardiomyocytes were isolated from neonatal day 1 C57BL/6J mice using enzymatic digestion method. Cardiomyocytes were transfected with plasmids or small interfering RNA (siRNA). The cardiomyocytes transfected with DDX21-siRNA were assigned to the siDDX21 group, those transfected with the DDX21 plasmid were assigned to the DDX21 group, and those transfected with the corresponding empty plasmid or siRNA were assigned to the NC group. Additionally, cardiomyocytes were treated with A-485 (A-485 group) or PBS (PBS group). An oxygen-glucose deprivation/reoxygenation (OGD/R) model was used to simulate cellular injury. Transcriptome sequencing was performed to identify downstream mechanisms of DDX21. Differential gene expression analysis was conducted using software such as DESeq2, and alternative splicing events in the mRNA transcriptome were analyzed using rMATS software. Mitochondrial superoxide, mitochondrial membrane potential, ATP content, and mitochondrial respiratory chain complex enzyme activity in cardiomyocytes were detected using immunofluorescence staining and commercial assay kits. The oxidative phosphorylation level of the cells was assessed by the Seahorse extracellular flux analyzer. Acetylated DDX21 levels were measured using co-immunoprecipitation and Western blot assays.Results:The expression levels of DDX21 in myocardium from the Bama pigs and mice in the I/R injury model were significantly higher than those in the sham group (all P<0.001). Echocardiographic results showed that at 28 days post-surgery, compared to the I/R+NC group, the I/R+DDX21 group exhibited higher left ventricular ejection fraction and fractional shortening, while the I/R+sh-DDX21 group showed lower values; Masson staining results demonstrated that, compared to the I/R+NC group, the myocardial fibrosis area in the I/R+DDX21 group was significantly reduced, whereas it was significantly increased in the I/R+sh-DDX21 group (all P<0.001). Transcriptomic sequencing results suggested that DDX21 may influence myocardial injury by regulating mitochondrial metabolic activity. In vitro, compared to the OGD/R+NC group, the OGD/R+DDX21 group exhibited lower mitochondrial superoxide levels, higher polymer/monomer ratio, maximal oxygen consumption, reserve capacity, and ATP content. In contrast, the OGD/R+siDDX21 group showed the opposite results, with reduced activity of mitochondrial respiratory chain complex V (all P<0.05). Mechanistically, rMATS software and other analyses indicated that knockdown of DDX21 affected the alternative 3′ splicing sites of ATP5J precursor mRNA, inhibiting the splicing of certain exonic sequences. Overexpression of DDX21 upregulated both mRNA and protein levels of ATP5J. Co-immunoprecipitation experiments showed that, compared to the PBS group, acetylated DDX21 levels were reduced in the A-485 group. Further in vivo experiments showed that, compared to the I/R+PBS group, the I/R+A-485 group exhibited higher left ventricular ejection fraction and fractional shortening, and a lower proportion of left ventricular fibrosis (all P<0.001). Conclusions:DDX21 improves cardiomyocyte energy metabolism and alleviates I/R injury by regulating the alternative splicing of ATP5J. A-485 holds potential as a novel small molecule candidate for the treatment of myocardial injury.