Objective:To evaluate the acute toxicities and related influencing factors of vertebral-body-sparing proton craniospinal irradiation (VBSpCSI) using pencil beam scanning (PBS) technology in pediatric patients, and to assess spinal growth and survival outcomes.Methods:A retrospective analysis was conducted on 70 pediatric patients treated with PBS-based VBSpCSI at Hebei Yizhou Cancer Hospital between January 2020 and December 2022, and continued to follow up until November 2023. Acute toxicities were assessed, and linear regression analysis combined with receiver operating characteristic curve were employed to investigate the dose-effect relationship between vertebral dose and toxicities. Spinal growth after radiotherapy was evaluated by measuring the Cobb angle on follow-up MRI. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.Results:The median age of patients at the time of irradiation was 6 years (range, 2-16 years). Two patients (3%) developed grade ≥3 gastrointestinal toxicities, while 7 patients (10%) experienced grade 1 radiation-induced esophagitis. The nadirs of white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) during treatment were significantly negatively correlated with vertebral V 5 Gy ( P=0.009, 0.006, 0.001) and vertebral V 20 Gy ( P=0.007, 0.011, <0.001). When vertebral V 5 Gy<86.5% and vertebral V 20 Gy<73.2%, the incidence of grade ≥3 myelosuppression was significantly reduced ( P<0.001, =0.001). Additionally, younger patient age (in months) and concurrent chemotherapy were also significantly associated with increased acute hematologic toxicity. Among 43 patients with MRI follow-up, no scoliosis, kyphosis, or chronic lumbosacral pain was observed. The 3-year OS and PFS rates were 95.7% and 86.4%, respectively. Conclusions:PBS-based VBSpCSI in pediatric patients demonstrates manageable acute toxicities, with a clear dose-effect relationship between vertebral V 5 Gy , V 20 Gy and hematologic toxicities, and the incidence of non-hematological toxicities remains low. No adverse effects on spinal growth or survival outcomes were observed in the short term.

Objective:To investigate the effects and underlying mechanisms of silent information regulator 1(SIRT1)on the dysfunction of umbilical vein endothelial cells(HUVECs)induced by oxidized low-density lipoprotein(ox-LDL).Methods:The impact of ox-LDL on the viability of HUVEC was assessed using the Cell Counting Kit-8(CCK-8)assay, which also facilitated the determination of the optimal ox-LDL concentration.Subsequent to ox-LDL treatment, several parameters were evaluated, including reactive oxygen species(ROS)production, apoptosis, migration, and angiogenesis, utilizing a ROS detection kit, flow cytometry, a Transwell migration assay, and an angiogenesis assay, respectively.The expression levels of apoptosis-related proteins, namely cleaved caspase-3(c-caspase-3), Bcl-2-associated X protein(Bax), B-cell lymphoma-2(Bcl-2), SIRT1, and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α), were quantified using Western blot analysis.Adenoviral vectors were employed to either overexpress or silence SIRT1, while the ROS inhibitor N-acetylcysteine(NAC)was applied to assess its effects on cell function.Additionally, PGC-1α acetylation(Ac-Lys)was investigated through co-immunoprecipitation.Results:In the oxidative model of ox-LDL-stimulated HUVECs, compared to controls, we observed a significant increase in ROS-positive cells(35.9±3.1 vs.5.4±0.9), heightened apoptosis(16.3±0.9 vs.7.6±0.7), diminished endothelial cell migration capacity, and reduced angiogenic capacity.Additionally, there was an elevation in the pro-apoptotic protein c-caspase3 and Bax, alongside a decrease in the anti-apoptotic protein bcl-2.Furthermore, SIRT1 expression was increased, as was the expression of PGC-1α.In comparison to the GFP group(28.5±1.9), the reduction in SIRT1 expression resulted in an increase in apoptosis(37.0±1.9).Conversely, overexpression of SIRT1 mitigated ox-LDL-induced apoptosis(25.2±1.6)(all P<0.05).Notably, the expression levels of PGC-1α and SIRT1 exhibited consistent changes: PGC-1α expression increased with SIRT1 overexpression and decreased when SIRT1 expression was reduced(both P<0.05).The administration of NAC to the ox-LDL-treated group led to a reduction in ROS production( t=11.18, P<0.01)and a significant enhancement in cell function.Immunoprecipitation results indicated that SIRT1 overexpression decreased ox-LDL-induced PGC-1α acetylation( t=18.18, P<0.01), whereas silencing of SIRT1 further increased PGC-1α acetylation levels( t=-19.09, P<0.01). Conclusions:SIRT1 is shown to protect against ox-LDL-induced apoptosis and dysfunction in HUVECs by deacetylating and activating PGC-1α, thereby highlighting its therapeutic potential in the context of endothelial cell injury.

Objective:To evaluate the acute toxicities and related influencing factors of vertebral-body-sparing proton craniospinal irradiation (VBSpCSI) using pencil beam scanning (PBS) technology in pediatric patients, and to assess spinal growth and survival outcomes.Methods:A retrospective analysis was conducted on 70 pediatric patients treated with PBS-based VBSpCSI at Hebei Yizhou Cancer Hospital between January 2020 and December 2022, and continued to follow up until November 2023. Acute toxicities were assessed, and linear regression analysis combined with receiver operating characteristic curve were employed to investigate the dose-effect relationship between vertebral dose and toxicities. Spinal growth after radiotherapy was evaluated by measuring the Cobb angle on follow-up MRI. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.Results:The median age of patients at the time of irradiation was 6 years (range, 2-16 years). Two patients (3%) developed grade ≥3 gastrointestinal toxicities, while 7 patients (10%) experienced grade 1 radiation-induced esophagitis. The nadirs of white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) during treatment were significantly negatively correlated with vertebral V 5 Gy ( P=0.009, 0.006, 0.001) and vertebral V 20 Gy ( P=0.007, 0.011, <0.001). When vertebral V 5 Gy<86.5% and vertebral V 20 Gy<73.2%, the incidence of grade ≥3 myelosuppression was significantly reduced ( P<0.001, =0.001). Additionally, younger patient age (in months) and concurrent chemotherapy were also significantly associated with increased acute hematologic toxicity. Among 43 patients with MRI follow-up, no scoliosis, kyphosis, or chronic lumbosacral pain was observed. The 3-year OS and PFS rates were 95.7% and 86.4%, respectively. Conclusions:PBS-based VBSpCSI in pediatric patients demonstrates manageable acute toxicities, with a clear dose-effect relationship between vertebral V 5 Gy , V 20 Gy and hematologic toxicities, and the incidence of non-hematological toxicities remains low. No adverse effects on spinal growth or survival outcomes were observed in the short term.

Objective:To investigate the effects and underlying mechanisms of silent information regulator 1(SIRT1)on the dysfunction of umbilical vein endothelial cells(HUVECs)induced by oxidized low-density lipoprotein(ox-LDL).Methods:The impact of ox-LDL on the viability of HUVEC was assessed using the Cell Counting Kit-8(CCK-8)assay, which also facilitated the determination of the optimal ox-LDL concentration.Subsequent to ox-LDL treatment, several parameters were evaluated, including reactive oxygen species(ROS)production, apoptosis, migration, and angiogenesis, utilizing a ROS detection kit, flow cytometry, a Transwell migration assay, and an angiogenesis assay, respectively.The expression levels of apoptosis-related proteins, namely cleaved caspase-3(c-caspase-3), Bcl-2-associated X protein(Bax), B-cell lymphoma-2(Bcl-2), SIRT1, and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α), were quantified using Western blot analysis.Adenoviral vectors were employed to either overexpress or silence SIRT1, while the ROS inhibitor N-acetylcysteine(NAC)was applied to assess its effects on cell function.Additionally, PGC-1α acetylation(Ac-Lys)was investigated through co-immunoprecipitation.Results:In the oxidative model of ox-LDL-stimulated HUVECs, compared to controls, we observed a significant increase in ROS-positive cells(35.9±3.1 vs.5.4±0.9), heightened apoptosis(16.3±0.9 vs.7.6±0.7), diminished endothelial cell migration capacity, and reduced angiogenic capacity.Additionally, there was an elevation in the pro-apoptotic protein c-caspase3 and Bax, alongside a decrease in the anti-apoptotic protein bcl-2.Furthermore, SIRT1 expression was increased, as was the expression of PGC-1α.In comparison to the GFP group(28.5±1.9), the reduction in SIRT1 expression resulted in an increase in apoptosis(37.0±1.9).Conversely, overexpression of SIRT1 mitigated ox-LDL-induced apoptosis(25.2±1.6)(all P<0.05).Notably, the expression levels of PGC-1α and SIRT1 exhibited consistent changes: PGC-1α expression increased with SIRT1 overexpression and decreased when SIRT1 expression was reduced(both P<0.05).The administration of NAC to the ox-LDL-treated group led to a reduction in ROS production( t=11.18, P<0.01)and a significant enhancement in cell function.Immunoprecipitation results indicated that SIRT1 overexpression decreased ox-LDL-induced PGC-1α acetylation( t=18.18, P<0.01), whereas silencing of SIRT1 further increased PGC-1α acetylation levels( t=-19.09, P<0.01). Conclusions:SIRT1 is shown to protect against ox-LDL-induced apoptosis and dysfunction in HUVECs by deacetylating and activating PGC-1α, thereby highlighting its therapeutic potential in the context of endothelial cell injury.

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) monoclonal antibody in maintenance therapy for ulcerative colitis (UC) .Methods:A retrospective case control study was conducted, including 84 patients with active UC undergoing VDZ therapy for an average of (22±8) weeks in the Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine from December 2020 to September 2023. These patients achieved a response or remission by (22±8) weeks and continued follow-up until (54±8) weeks. They were divided into effective and ineffective groups based on whether they achieved clinical remission by (54±8) weeks after using VDZ; those who required optimized treatment with shortened injection intervals were included in the ineffective group. Baseline clinical data, medication history and endoscopic imaging data were recorded. The clinically modified Mayo score, Mayo endoscopic score, and other assessments were used to evaluate UC disease activity. Adverse reactions related to treatment were also recorded to assess the efficacy of VDZ treatment up to (54±8) weeks was assessed and key factors affecting clinical remission of the disease were analyzed.Results:Among the 84 UC patients with followed up to (54±8) weeks, 47 cases (55.95%) achieved clinical remission and were classified as the effective group, while 37 cases (44.05%) did not achieve clinical remission and were classified as the ineffective group. The endoscopic remission rate in the effective group was 68.09% (32/47), and the mucosal healing rate was 36.17% (17/47). Joint pain occurred in 2.38% of patients, hepatic dysfunction in 3.57%, and one patient died from leukemia following a COVID-19 infection during the maintenance therapy period.Conclusion:VDZ has a certain efficacy in the continuous treatment of UC patients and in maintaining clinical and endoscopic remission, with generally high overall safety and a low incidence of adverse reactions.

Objective:To evaluate the role of nuclear factor erythroid 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in the improvement in postoperative cognitive function by electroacupuncture preconditioning in aged rats.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 24 months, weighing 550-600 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (C group), POCD group, electroacupuncture+ POCD group (EA group), and Nrf2 inhibitor ML385+ electroacupuncture+ POCD group (I group). A rat POCD model was prepared by performing exploratory laparotomy under 3% sevoflurane anesthesia. Nrf2 inhibitor ML385 15 mg/kg was intraperitoneally injected at 30 min before surgery in group I, while the equal volume of normal saline was given instead in the remaining groups. Electroacupuncture stimulation of the Zusanli, Hegu and Neiguan acupoints (disperse-dense waves, current intensity 1 mA, frequency 2/15 Hz, 30 min) was performed at 8: 00 a.m. every day for 5 days prior to model preparation in EA group and I group. An open field test was conducted at 3 days after operation to measure the autonomous motor function, and Morris water maze test was conducted after the end of the open field test at 3-7 days after operation to evaluate the cognitive function. After the Morris water maze test, the rats were sacrificed under anesthesia and hippocampal tissues were taken for determination of the level of reactive oxygen species (ROS, by flow cytometry) and expression of Nrf2 and HO-1 (by Western blot) and for examination of the mitochondrial ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was decreased, the hippocampal ROS levels were increased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and mitochondria were swollen and mitochondrial cristae were broken in the hippocampal CA1 neurons in group POCD. Compared with group POCD, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the hippocampal ROS levels were decreased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the swelling of mitochondria and rupture of cristae structure were improved in the hippocampal CA1 neurons in group EA. Compared with group EA, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was decreased, the hippocampal ROS levels were increased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the swelling of mitochondria and rupture of cristae structure were aggravated in the hippocampal CA1 neurons in group I. Conclusions:Activation of the hippocampal Nrf2/HO-1 signaling pathway is involved in improvement in postoperative cognitive function by electroacupuncture preconditioning in aged rats.

Objective:To analyze the pathogen distribution and prognostic risk factors of catheter-related bloodstream infection (CRBSI) in patients with maintenance hemodialysis (MHD) during non-hospitalization.Methods:A retrospective comparative study was conducted. Thirty-four patients of MHD with semi-permanent catheter admitted to the department of nephrology of Gansu Provincial Hospital from January 2020 to May 2023 due to CRBSI during non-hospitalization were enrolled. The distribution characteristics of pathogens causing CRBSI in MHD patients during non-hospital period were analyzed. All patients were actively given anti-infection treatment after admission. The general data, laboratory indicators and prognosis during hospitalization were collected through the electronic medical record system. Patients were divided into poor prognosis group (14 cases) and good prognosis group (20 cases) according to the treatment results during hospitalization. Univariate and binary Logistic regression were used to analyze the risk factors affecting the prognosis of patients, and receiver operator characteristic curve (ROC curve) was drawn to evaluate its predictive value for prognosis.Results:A total of 28 pathogenic bacteria were isolated from 34 patients, of which 25 were Gram-positive, Staphylococcus was the most common pathogen, accounting for 82.15% of the total, and 16 strains of Staphylococcus aureus (57.15%), including 6 methicillin-resistant Staphylococcus aureus (MRSA, 21.43%). There were 7 strains of Staphylococcus epidermidis (25.00%), including 3 strains of methicillin-resistant Staphylococcus epidermidis (MRSE, 10.71%). There were 3 strains of Gram-negative bacteria, 1 strain each of Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii. Univariate analysis showed that the fever duration of MHD patients with CRBSI in the poor prognosis group was significantly longer than that in the good prognosis group [days: 8.50 (3.75, 45.00) vs. 2.50 (1.00, 4.75), P < 0.01], serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and random blood glucose (GLU) were significantly higher than those in the good prognosis group [ESR (mm/1 h): 82.36±24.98 vs. 56.95±35.65, CRP (mg/L): 123.45±74.10 vs. 67.35±55.22, GLU (mmol/L): 8.74±3.66 vs. 6.42±1.95, all P < 0.05]. Binary Logistic regression analysis showed that serum CRP was an independent risk factor for poor prognosis in MHD patients with CRBSI [odds ratio ( OR) = 1.020, 95% confidence interval (95% CI) was 1.002-1.038, P = 0.025]. ROC curve analysis showed that the area under the curve (AUC) of serum CRP in predicting poor prognosis of MHD patients with CRBSI was 0.711; when the optimal cut-off value was 104.65 mg/L, the sensitivity was 64.3% and the specificity was 85.0%, indicating that it has good predictive value. Conclusions:Gram-positive bacteria are the main pathogens of CRBSI in MHD patients during non-hospital period. The poor prognosis is mainly related to the high level of serum CRP. Serum CRP level can effectively screen the high-risk group of MHD patients with CRBSI with poor prognosis.

Objective:To document any effect of combining kinesiotaping (KT) with Monitored Rehab Systems biofeedback training (MRS training) on the recovery of knee function after anterior cruciate ligament reconstruction (ACLR).Methods:Twenty-two patients after ACLR were randomly divided into an MRS group and a combined group, each of 11. In addition to conventional rehabilitation training, the MRS group had placebo taping in place during their MRS training, while the combined group had KT applied. Each training session lasted 45 minutes, with three sessions per week. Before the experiment and after 8 weeks of treatment, the affected foot support phase, impulse of each area of the affected foot′s sole, and lower limb reaction time were measured.Results:Significant improvement in the affected foot′s support phase and lower limb reaction time was documented in both groups, as well as in the average impulse percentage of the affected foot′s plantar forefoot area (F area), mid-foot area (MF area), and heel area (H area). All were significantly better in the combined group than in the MRS group, on average.Conclusion:Supplementing MRS biofeedback training with kinesiotaping can more effectively improve the knee joint functioning and postural control of patients after ACLR surgery. The combination is worthy of clinical promotion and application.

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) monoclonal antibody in maintenance therapy for ulcerative colitis (UC) .Methods:A retrospective case control study was conducted, including 84 patients with active UC undergoing VDZ therapy for an average of (22±8) weeks in the Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine from December 2020 to September 2023. These patients achieved a response or remission by (22±8) weeks and continued follow-up until (54±8) weeks. They were divided into effective and ineffective groups based on whether they achieved clinical remission by (54±8) weeks after using VDZ; those who required optimized treatment with shortened injection intervals were included in the ineffective group. Baseline clinical data, medication history and endoscopic imaging data were recorded. The clinically modified Mayo score, Mayo endoscopic score, and other assessments were used to evaluate UC disease activity. Adverse reactions related to treatment were also recorded to assess the efficacy of VDZ treatment up to (54±8) weeks was assessed and key factors affecting clinical remission of the disease were analyzed.Results:Among the 84 UC patients with followed up to (54±8) weeks, 47 cases (55.95%) achieved clinical remission and were classified as the effective group, while 37 cases (44.05%) did not achieve clinical remission and were classified as the ineffective group. The endoscopic remission rate in the effective group was 68.09% (32/47), and the mucosal healing rate was 36.17% (17/47). Joint pain occurred in 2.38% of patients, hepatic dysfunction in 3.57%, and one patient died from leukemia following a COVID-19 infection during the maintenance therapy period.Conclusion:VDZ has a certain efficacy in the continuous treatment of UC patients and in maintaining clinical and endoscopic remission, with generally high overall safety and a low incidence of adverse reactions.

Objective:To evaluate the role of nuclear factor erythroid 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in the improvement in postoperative cognitive function by electroacupuncture preconditioning in aged rats.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 24 months, weighing 550-600 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (C group), POCD group, electroacupuncture+ POCD group (EA group), and Nrf2 inhibitor ML385+ electroacupuncture+ POCD group (I group). A rat POCD model was prepared by performing exploratory laparotomy under 3% sevoflurane anesthesia. Nrf2 inhibitor ML385 15 mg/kg was intraperitoneally injected at 30 min before surgery in group I, while the equal volume of normal saline was given instead in the remaining groups. Electroacupuncture stimulation of the Zusanli, Hegu and Neiguan acupoints (disperse-dense waves, current intensity 1 mA, frequency 2/15 Hz, 30 min) was performed at 8: 00 a.m. every day for 5 days prior to model preparation in EA group and I group. An open field test was conducted at 3 days after operation to measure the autonomous motor function, and Morris water maze test was conducted after the end of the open field test at 3-7 days after operation to evaluate the cognitive function. After the Morris water maze test, the rats were sacrificed under anesthesia and hippocampal tissues were taken for determination of the level of reactive oxygen species (ROS, by flow cytometry) and expression of Nrf2 and HO-1 (by Western blot) and for examination of the mitochondrial ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was decreased, the hippocampal ROS levels were increased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and mitochondria were swollen and mitochondrial cristae were broken in the hippocampal CA1 neurons in group POCD. Compared with group POCD, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the hippocampal ROS levels were decreased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the swelling of mitochondria and rupture of cristae structure were improved in the hippocampal CA1 neurons in group EA. Compared with group EA, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was decreased, the hippocampal ROS levels were increased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the swelling of mitochondria and rupture of cristae structure were aggravated in the hippocampal CA1 neurons in group I. Conclusions:Activation of the hippocampal Nrf2/HO-1 signaling pathway is involved in improvement in postoperative cognitive function by electroacupuncture preconditioning in aged rats.