Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

Objective To examine the expression and validate the localization of the neurotrophin neuritin(NRN1)in human tissues using bioinformatics and experimental methods.Methods The tissue-specific expression of NRN1 was analyzed using the Human Pro-tein Atlas(HPA)database.NRN1 mRNA and protein expression were experimentally validated using real-time quantitative PCR and immunohistochemistry,respectively.A pEGFP-C1-NRN1 green fluorescent protein fusion vector was transfected into 293 cells,and NRN1 localization was assessed using immunofluorescence.Endogenous NRN1 localization was also examined in hippocampal HT22 cells.Results According to the HPA database,NRN1 expression was enriched in the cerebral cortex,parathyroid gland,adipose tissue,and placenta.Experimental validation confirmed NRN 1 expression in all the aforementioned tissues,with highest levels observed in the brain and spleen.Immunofluorescence analysis revealed that NRN 1 was predominantly localized to the membrane in HT22 cells and to the cyto-plasm in 293 cells.Conclusion NRN 1 is expressed in various human tissues,with notably high expression in the brain.It is primarily localized to the cell membrane and cytoplasm.

Objective To examine the expression and validate the localization of the neurotrophin neuritin(NRN1)in human tissues using bioinformatics and experimental methods.Methods The tissue-specific expression of NRN1 was analyzed using the Human Pro-tein Atlas(HPA)database.NRN1 mRNA and protein expression were experimentally validated using real-time quantitative PCR and immunohistochemistry,respectively.A pEGFP-C1-NRN1 green fluorescent protein fusion vector was transfected into 293 cells,and NRN1 localization was assessed using immunofluorescence.Endogenous NRN1 localization was also examined in hippocampal HT22 cells.Results According to the HPA database,NRN1 expression was enriched in the cerebral cortex,parathyroid gland,adipose tissue,and placenta.Experimental validation confirmed NRN 1 expression in all the aforementioned tissues,with highest levels observed in the brain and spleen.Immunofluorescence analysis revealed that NRN 1 was predominantly localized to the membrane in HT22 cells and to the cyto-plasm in 293 cells.Conclusion NRN 1 is expressed in various human tissues,with notably high expression in the brain.It is primarily localized to the cell membrane and cytoplasm.

Objective:To explore the clinical efficacy of combined use of artificial bone materials in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCF).Methods:One hundred and eighty-four consecutive patients with OVCF admitted to Beijing Friendship Hospital, Capital Medical University from June 2020 to June 2021 were retrospectively analyzed. All patients had single-level fracture and treated with PVP. According to whether artificial bone materials were used, the patients were divided into experimental group ( n=95) and control group ( n=89). The experimental group was treated with bone cement mixed with artificial bone materials, and the control group was treated with bone cement. The following indices were observed in the two groups before surgery and at 3 days, 3 months, 12 months (final follow-up) after surgery: visual analogue scale (VAS) score, Oswestry disability index (ODI), Cobb angle of kyphosis, and the percentage of anterior vertebral height, the amount of bone cement injected, postoperative complications and adjacent vertebral fractures were recorded. Measurement data were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between groups; Chi- test was used for comparison between groups for count data. Results:All patients successfully completed the operation and were followed up for 12-20 months, with a mean follow-up of (14.24±2.51) months. The VAS score at 3 days, 3 months after operation and final follow-up (experimental group: 2.00±0.71, 1.89±0.71, 1.41±0.49; control group: 2.13±0.73, 1.81±0.60, 1.44±0.50) and ODI index at 3 months after operation and the final follow-up [experimental group: (21.56±4.68)%, (23.22±4.11)%; control group: (22.46±3.74)%, (22.39±4.05)%] were significantly improved compared with those before operation [VAS, experimental group: 7.66±0.86, control group: 7.81±0.89; ODI, experimental group: (70.11±8.24)%, control group: (68.97±8.59)%], and the differences were statistically significant ( P<0.05). There were no significant differences in the amount of bone cement injected between the two groups ( P>0.05). There was no significant difference in the Cobb angle of kyphosis and the percentage of anterior vertebral height at each time point ( P>0.05). The incidence of bone cement leakage in the experimental group was 15.8% (15/95), slightly lower than that in the control group [22.5% (20/89)], but the difference was not statistically significant ( P>0.05). As of the final follow-up, the incidence of adjacent vertebral fracture in the experimental group was 8.4% (8/95), which was lower than that in the control group (19.1%, 17/89), and the difference was statistically significant ( P< 0.05). Conclusion:The application of bone cement mixed with artificial bone materials in PVP for OVCF, can achieve good clinical efficacy, and reduce the incidence of adjacent vertebral fractures.

Objective To investigate the value of thrombomodulin(TM),thrombin-antithrombin complex(TAT),α2 plasmin inhibitor-plasmin complex(PIC)and tissue plasminogen activator-inhibitor complex(t-PAIC)in the diagnosis and prognosis of neonatal disseminated intravascular coagulation(DIC).Methods Eighty-seven DIC neonates(the observation group)were included and divided into the survival group(66 cases)and the death group(21 cases)based on their outcomes at discharge.And 50 healthy newborns born in the same period were selected as the control group.The clinical data of neonates were collected,and risk factors of neonatal DIC were analyzed by Logistic regression.The differences of TM,TAT,PIC and t-PAIC levels in different groups were analyzed.The receiver operating characteristic(ROC)curve was used to analyze values of TM,TAT,PIC and t-PAIC in the diagnosis and prognosis of neonatal DIC.Results The incidence of low Apgar score,birth asphyxia,IVH,sepsis and maternal pregnancy induced hypertension syndrome(PIH)were higher in the observation group than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that low Apgar score,birth asphyxia,sepsis and PIH were independent risk factors for neonatal DIC.TM,TAT,PIC and t-PAIC levels were higher in the observation group than those in the control group(P＜0.05).ROC curve showed that the combined diagnosis value of TM,TAT,PIC and t-PAIC was better than that of single diagnosis of neonatal DIC.TM and TAT levels were higher in the death group than those in the survival group(P＜0.05),and there were no significant differences in PIC and t-PAIC levels between the two groups.Multivariate Logistic regression analysis showed that elevated TAT level was an independent risk factor for neonatal DIC prognosis.ROC curve showed that when TAT was 21.72 μg/L,the area under the curve for predicting neonatal DIC prognosis was 0.772(95%CI:0.666-0.878),and the sensitivity and specificity were 76.2%and 71.2%,respectively.Conclusion The combined application of TM,TAT,PIC and t-PAIC has important clinical value in diagnosis and prognosis evaluation of neonatal DIC.

Objective:To investigate the efficacy and safety of Ropivacaine combined with Lidocaine for incision infiltration anesthesia in lumbar fusion surgery.Methods:The case data of 154 patients with lumbar degenerative diseases who underwent lumbar fusion surgery at the Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University from March 2021 to September 2023 were retrospectively analyzed, and the patients were divided into the experimental group ( n=72) and the control group ( n=82) according to whether or not they underwent Ropivacaine combined with Lidocaine incisional infiltration anesthesia. The experimental group was anesthetized with Ropivacaine combined with Lidocaine incisional infiltration anesthesia, and the control group was not anesthetized with incisional infiltration. The static and dynamic pain visual analog score (VAS) at six postoperative time points (2, 4, 6, 12, 24, 48 h after surgery), the application of postoperative analgesic medications, and related complications were compared between the two groups. The measurement data of normal distribution were expressed as mean±standard deviation( ± s), and t-test was used for comparison between groups, the measurement data of non-normal distribution were expressed as median (interquartile distance) [ M( Q1, Q3)], and non-parametric test was used for comparison between groups; the count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Results:All patients underwent successful surgery, and the static [(4.40±1.67), (3.86±1.22), (3.58±1.15), (3.43±1.11) points] and dynamic [(4.56±1.69), (4.03±1.21), (3.79±1.16), (3.65±1.13) points] VAS scores of the patients in the experimental group were lower than those in the control group [static: (5.38±1.73), (5.06±1.58), (4.68±1.37), (3.82±1.22) points; dynamic: (5.55±1.62), (5.29±1.50), (4.89±1.41), (4.12±1.29) points] at 2, 4, 6, 12 h after surgery, and the differences were statistically significant ( P<0.05); at 24, 48 h after surgery, there was no significant difference in the static and dynamic VAS scores between the two groups ( P>0.05). The dosage of oral Tramadol [100(0, 100) mg] and subcutaneous injection of Morphine [0(0, 0) mg] in the experimental group at 48 h after surgery were significantly lower than those in the control group [100(100, 100), 0(0, 10) mg], and the differences were statistically significant ( P<0.05). There was no significant difference in the incidence of postoperative incision complications and cerebrospinal fluid leakage between the two groups ( P>0.05). Conclusion:Ropivacaine combined with Lidocaine for incision infiltration anesthesia in lumbar fusion surgery can effectively relieve early pain in the surgical area, reduce the use of postoperative analgesic medications, and will not increase related complications.

Objective:To evaluate effect of diammonium glycyrrhizinate(DG)on lipopolysaccharide(LPS)-induced TLR4/NF-κB inflammatory signaling pathway in BV2 microglial cells and to explore its potential regulatory mechanisms on ameliorating neu-roinflammation.Methods:BV2 microglia injury model was induced by LPS and treated with 20 and 60 μmol/L DG.MTS was used to determine vitality of cells.NO level secreted by cells was detected by Griess.Inflammatory factors TNF-α,IL-6,and IL-1β levels in cell supernatant were measured by ELISA.TNF-α,IL-6,IL-1β,TLR4 and MyD88 mRNA levels were detected by RT-qPCR.Western blot was used to determine expressions of TLR4,MyD88,NF-κB,p-NF-κB,IκB-α and p-IκB-α proteins of cells.Results:Compared with control group,LPS-treated BV2 microglia had significantly lower viability(P<0.05),significantly higher NO secretion(P<0.05),significantly up-regulation levels of inflammatory factors TNF-α,IL-6 and IL-1β(P<0.05),and significantly higher mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),TLR4,MyD88,NF-κB,p-NF-κB,IκB-α,and p-IκB-α protein expressions were significantly increased(P<0.05).Compared with LPS group,BV2 microglia intervened with different concentrations of DG had significantly higher viability(P<0.05),significantly lower NO secretion(P<0.05),significantly lower TNF-α,IL-6 and IL-1β inflammatory factors levels(P<0.05),significantly lower mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),and TLR4,MyD88,p-NF-κB and p-IκB-α protein expressions were significantly reduced(P<0.05).Conclusion:DG can inhibit LPS-induced neuroinflammatory responses in microglia,whose underlying mechanism is suppression of TLR4/NF-κB signaling pathway.

Objective:To investigate the effectiveness of preeclampsia risk prediction models based on maternal risk factors during the first trimester in a local population.Methods:This was a diagnostic study. Pregnant women who underwent prenatal examination in People′s Hospital of Rizhao from May 2019 to May 2022 and had risk factors for preeclampsia were enrolled at 11-13 +6 weeks gestation, and were divided into preterm preeclampsia group, term preeclampsia group and non-preeclampsia group according to the occurrence and the gestational week. Baseline clinical data were collected. The effectiveness of different models in predicting preeclampsia risk was evaluated using receiver operating characteristic (ROC) curves. Results:Among the 559 pregnant women enrolled, 78(14.0%) had preeclampsia, including 35(6.3%) with preterm preeclampsia (preterm preeclampsia group), 43 (7.7%) with term preeclampsia (term preeclampsia group), and 481 (86.0%) without preeclampsia (non-preeclampsia group).The most effective model for predicting preterm preeclampsia in the first trimester was maternal risk factor+mean arterial pressure (MAP)+serum placental growth factor (PLGF)+uterine artery pulse index (UTPI). The area under ROC curve was 0.805, and the sensitivity was 56.6% with a false-positive rate of 10%; the most effective model for predicting term preeclampsia and preeclampsia was maternal risk factor+MAP+UTPI. The area under ROC curve was 0.777, and the sensitivity was 52.6% and 53.5% with a false-positive rate of 10%.Conclusion:The combined predicting strategy for preterm preeclampsia based on maternal risk factors in the first trimester maybe effective among our population.

Objective:To observe the clinical efficacy of manual therapy based on the Discovery of Posture Secret (DPS) in treating adolescent idiopathic scoliosis (AIS).Methods:Thirty-six AIS patients were randomly divided into an observation group of 17 and a control group of 16. In addition to 10 minutes of side-shift training each week, the control group was given 20 minutes of sling exercise training (SET), while the observation group underwent weekly 20-minute manual therapy sessions based on DPS on the days without SET. Before and after the 4 weeks of treatment spine curvature (Cobb angle), clavicular angle (CA), angle of trunk rotation (ATR) and vertebral rotation (VR) were measured, and the Scoliosis Research Society′s patient questionnaire 22 (SRS-22) was administered.Results:After the treatment the average Cobb angle, CA, ATR and SRS-22 score of the observation group had improved significantly compared with before the treatment. The average Cobb angle, ATR and SRS-22 score of the control group were also significantly higher, but the improvements were not as great as in the observation group. There was no significant difference in VR improvement between the two groups.Conclusion:Manual therapy based on the DPS can effectively ameliorate the scoliosis and shoulder imbalance of AIS patients.

Objective:To observe any effect of bilateral high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on the swallowing of stroke survivors with dysphagia.Methods:Thirty-eight patients with post-stroke dysphagia were randomly divided into a cerebellar stimulation group of 20 and a sham group of 18. In addition to drug therapy and physical rehabilitation training, the cerebellar stimulation group received 500 pulses of rTMS of the cerebellum daily at 10Hz and 120% of the resting movement threshold lasting 1s at 9s intervals. The sham stimulation group was treated with sham rTMS (with the angle between the stimulation coil and the scalp at 90°). Twenty minutes later, both groups were given 30 minutes of routine swallowing training daily by the same speech therapist. The treatment was administered 5 times a week for 3 weeks. Before the treatment and afterward, both groups′ swallowing was evaluated y videofluoroscopic swallowing study (VFSS), using a functional dysphagia scale (FDS) and using the Rosenbek penetration aspiration scale (PAS). Oral transport time, swallowing response time, pharyngeal transport time, laryngeal vestibular closure time and upper esophageal sphincter opening duration were recorded, and the changes in swallowing function and swallowing time parameters before and after the treatment were compared between the two groups.Results:Before the stimulation there were no significant differences between the two groups. Afterward, the average PAS and FDS scores of both groups had improved significantly, but with significantly greater improvement in the cerebellar stimulation group than in the sham group. Average oral transit time and swallow response time had shortened significantly, but with significantly shorter time, on average, in the cerebellar stimulation group.Conclusion:Bilateral high-frequency rTMS of the cerebellum can improve the swallowing of persons with dysphagia, and shorten their oral transit time and swallow response time.