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.

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.

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.

The PI3K/Akt signaling pathway,a critical intracellular regulatory network,plays a piv-otal role in diverse physiological processes,including cell survival,proliferation,metabolism,and immune regulation.Current research has transitioned from elucidating fundamental molecular mechanisms to exploring novel dimensions within the host-pathogen interaction regulatory net-work.This shift emphasizes uncovering molecular strategies employed by pathogens to evade host immune clearance by hijacking or inhibiting this pathway,as well as developing targeted anti-infec-tion therapies specific to this pathway.This article delineates the components and activation mecha-nisms of the PI3K/Akt pathway and reviews its specific roles in mediating immune defense,im-mune evasion,and host tissue damage during bacterial infections.Furthermore,it evaluates the po-tential of targeting this pathway as a therapeutic strategy for infectious diseases.By synthesizing existing research and providing future perspectives,this review aims to advance the understanding of bacterial infection pathogenesis and inform the development of non-antibiotic therapies targeting host signaling pathways.

The PI3K/Akt signaling pathway,a critical intracellular regulatory network,plays a piv-otal role in diverse physiological processes,including cell survival,proliferation,metabolism,and immune regulation.Current research has transitioned from elucidating fundamental molecular mechanisms to exploring novel dimensions within the host-pathogen interaction regulatory net-work.This shift emphasizes uncovering molecular strategies employed by pathogens to evade host immune clearance by hijacking or inhibiting this pathway,as well as developing targeted anti-infec-tion therapies specific to this pathway.This article delineates the components and activation mecha-nisms of the PI3K/Akt pathway and reviews its specific roles in mediating immune defense,im-mune evasion,and host tissue damage during bacterial infections.Furthermore,it evaluates the po-tential of targeting this pathway as a therapeutic strategy for infectious diseases.By synthesizing existing research and providing future perspectives,this review aims to advance the understanding of bacterial infection pathogenesis and inform the development of non-antibiotic therapies targeting host signaling pathways.

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.

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 investigate the biological role and molecular mechanism of checkpoint kinase 1 (CHK1) in delaying cardiac aging in mice.Methods:In vitro, a senescence model of H9C2 cells (a cardiomyocyte line) was induced using H 2O 2. A control group (without H 2O 2 treatment) and three H 2O 2-treated groups (at concentrations of 10, 30, and 50 μmol/L) were set up. The CCK-8 assay was used to evaluate the proliferative activity of cells in each group; Western blot analysis was employed to detect the expression level of CHK1; and quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine the messenger RNA (mRNA) expression levels of P16 and interleukin-1β (IL-1β). In vivo, C57BL/6 wild-type mice aged 2 months ( n=15) and 24 months ( n=40), as well as myocardial-specific CHK1-overexpressing (CHK1-TG) mice aged 2 months ( n=15) and 24 months ( n=40), were selected. The mice were divided into four groups based on age and genotype: 2-month-old wild-type (WT-2M), 24-month-old wild-type (WT-24M), 2-month-old CHK1-TG (CHK1-TG-2M), and 24-month-old CHK1-TG (CHK1-TG-24M). Echocardiography was used to evaluate cardiac function of mice in the WT-24M and CHK1-TG-24M groups. Western blot analysis was conducted to measure the protein expression levels of CHK1, total Ras-related protein 1 (Rap1), NADPH oxidase 4 (Nox4), and Rap1-guanosine triphosphate (Rap1-GTP, the active form of Rap1) in the cardiac tissue of mice in each group. qRT-PCR was used to detect the messenger RNA (mRNA) expression levels of CHK1, collagen type Ⅰ (Coll1), matrix metalloproteinase-2 (Mmp2), alpha-smooth muscle actin (α-SMA), P53, P21, P16, thioredoxin 1 (Trx1), thioredoxin reductase (TrxR), glutathione recluctase (GR), Rap1, and Nox4. Immunofluorescence staining was employed to determine the protein expression levels of P53, P21, and P16, as well as the proportion of histone H2AX phosphorylation-positive cells. Dihydroethidium (DHE) staining was used to detect the relative intensity of DHE. Wheat germ agglutinin staining, HE staining, Masson staining and Sirius red staining were applied to measure the cross-sectional area of cardiomyocytes, cardiac morphology, and myocardial fibrosis area. Mice in the WT-24M and CHK1-TG-24M groups were intraperitoneally injected with the Rap1 activity inhibitor GGTI298 (25 μmol/kg). After injection, the oxidative stress damage in the cardiac tissue of the mice was detected, along with the mRNA expression levels of fibrosis-related indicators (Coll1, Mmp2, and α-SMA) and cell cycle inhibitory proteins (P16, P21, and P53). Results:A concentration of 30 μmol/L was determined as the optimal concentration for establishing an H 2O 2-induced senescence model of myocardial cells in vitro. The expression level of CHK1 in H9C2 cells of the 30 μmol/L H 2O 2 group was lower than that in the control group ( P<0.05). Echocardiographic examination showed that the left ventricular ejection fraction ((61.08±1.13)% vs. (52.55±2.02)%) and fractional shortening ((31.80±1.27)% vs. (25.18±1.59)%) of mice in the CHK1-TG-24M group were higher than those in the WT-24M group (both P<0.05). qRT-PCR and Western blot analysis revealed that, compared with the WT-24M group, mice in CHK1-TG-24M group had higher expression levels of CHK1 and its mRNA, lower expression levels of Nox4 and its mRNA, and higher expression level of Rap1-guanosine triphosphate (Rap1-GTP) (all P<0.05). However, there were no statistically significant differences in the total expression level of Rap1 and its mRNA between the two groups (both P>0.05). In addition, the mRNA expression levels of Coll1, Mmp2, and α-SMA in myocardial tissue of mice in the CHK1-TG-24M group were lower than those in the WT-24M group (all P<0.05). Immunofluorescence staining results showed that the expression levels of P53, P21, and P16 proteins, as well as the proportion of phosphorylated histone H2AX-positive cells in myocardial tissue of mice in the WT-24M group were higher than those in the CHK1-TG-24M group (all P<0.05). qRT-PCR further confirmed that the mRNA expression levels of the above-mentioned proteins in cardiac tissue of mice in the WT-24M group were higher than those in the CHK1-TG-24M group (all P<0.05). DHE staining results indicated that the relative intensity of DHE in cardiac tissue of mice in the CHK1-TG-24M group was lower than that in the WT-24M group ( P<0.05). Meanwhile, the left ventricular internal diameter, cross-sectional area of cardiomyocytes, and myocardial fibrosis area of mice in the CHK1-TG-24M group were all smaller than those in the WT-24M group (all P<0.05). Furthermore, the degree of DNA damage in cardiac tissue as well as the mRNA levels of fibrosis-related indicators (Coll1, Mmp2, and α-SMA) and cell cycle inhibitory proteins (P53, P21, P16) in mice of the WT-24M+GGTI298 group were higher than those in the WT-24M group and the CHK1-TG-24M+GGTI298 group (all P<0.05). Conclusion:CHK1 alleviates oxidative stress-induced damage in mouse cardiomyocytes by activating the Rap1/Nox4 signaling pathway, thereby delaying cardiac aging in mice.

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.