OBJECTIVE: To compare the effectiveness of different puncture methods of the flexible bone cement delivery device in unilateral percutaneous curved vertebroplasty for osteoporotic vertebral upper 1/3 compression fractures. METHODS: A retrospective analysis was conducted on the clinical data of 67 patients with osteoporotic vertebral upper 1/3 compression fractures who were admitted and met the selection criteria between January 2023 and April 2024. The patients were divided into two groups based on the puncture method of the flexible bone cement delivery device: the oblique puncture group ( n=37) and the parallel puncture group ( n=30). There was no significant difference ( P>0.05) between the two groups in terms of gender, age, bone mineral density (T value), distribution of fractured vertebrae, time from injury to operation, and preoperative visual analogue scale (VAS) score for pain, Oswestry disability index (ODI), anterior vertebral height of the fractured vertebra, and Cobb angle of the fractured vertebra. The following parameters were compared between the two groups: operation time, incidence of secondary puncture, incidence of bone cement leakage, volume of injected bone cement, bone cement distribution score, as well as VAS score, ODI, anterior vertebral height of the fractured vertebra, and Cobb angle of the fractured vertebra at 1 day after operation and at last follow-up. RESULTS: Two cases in the oblique puncture group and 7 cases in the parallel puncture group underwent secondary puncture during operation, and the difference in the incidence of secondary puncture was significant ( P<0.05). No complications such as bone cement hypersensitivity, bone cement embolism, nerve injury, or epidural hematoma occurred in both groups. There was no significant difference in operation time, volume of injected bone cement, incidence of bone cement leakage, distribution score and rating of bone cement between the two groups ( P>0.05). All patients were followed up 6-18 months (mean, 12.0 months), and there was no significant difference in the follow-up time between the two groups ( P>0.05). No further fracture collapse or compression occurred in the fractured vertebra during follow-up. Both groups exhibited significant improvements in VAS score, ODI, anterior vertebral height, and Cobb angle of the fractured vertebra after operation compared to baseline ( P<0.05). There were also significant differences between the two time points after operation ( P<0.05). However, there was no significant difference in the above indicators between the two groups ( P>0.05). CONCLUSION For osteoporotic vertebral upper 1/3 compression fractures treated with unilateral percutaneous curved vertebroplasty, both oblique and parallel puncture methods of the flexible bone cement delivery device can effectively relieve pain, but the former is more conducive to reducing the incidence of secondary puncture.
Humans ; Bone Cements/therapeutic use* ; Fractures, Compression/surgery* ; Retrospective Studies ; Vertebroplasty/instrumentation* ; Osteoporotic Fractures/surgery* ; Spinal Fractures/surgery* ; Female ; Male ; Aged ; Middle Aged ; Treatment Outcome ; Punctures/methods* ; Aged, 80 and over

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

BACKGROUND:Percutaneous curved vertebroplasty has the advantages of minimal trauma and bone cement dispersion,but whether it is safe and effective for the treatment of compression fractures in the upper 1/3 of the vertebral body needs further study.OBJECTIVE:To investigate the clinical efficacy of percutaneous curved vertebroplasty in the treatment of the upper 1/3 compression fractures of the osteoporotic vertebrae.METHODS:Medical records of 66 patients with osteoporotic thoracolumbar upper 1/3 compression fracture admitted to Department of Orthopedics of PLA Rocket Force Characteristic Medical Center from January 2020 to June 2023 were retrospectively analyzed.Among them,32 cases were treated with percutaneous curved vertebroplasty(observation group)and 34 cases were treated with"noncoplanar bipedicular puncture"percutaneous vertebroplasty(control group).Pain visual analog scale score,Oswestry Disability Index,anterior edge height of injured vertebra,and Cobb angle of injured vertebra were compared and analyzed between the two groups before surgery,the first day after surgery,and the last follow-up.The operative time,bone cement leakage rate,bone cement injection volume,and bone cement dispersion score of the two groups were statistically analyzed.RESULTS AND CONCLUSION:(1)The operations were successfully completed in both groups of patients,and no complications such as bone cement allergy,bone cement embolism,nerve damage,or epidural hematoma occurred.(2)Pain visual analog scale score,Oswestry disability index,anterior edge height,and Cobb angle of injured vertebra of the two groups at the first day after surgery and the last follow-up were all better than those before surgery,with statistically significant difference(P＜0.05),but there was no statistical significance between the two groups(P＞0.05).The Oswestry disability index of the two groups at the last follow-up was better than that on the first day after surgery(P＜0.05).(3)The operation time and bone cement leakage rate of the observation group were lower than those of the control group,and the differences were statistically significant(P＜0.05).(4)There were no significant differences in bone cement injection volume and bone cement dispersion score between the two groups(P＞0.05).(5)The results show that percutaneous curved vertebroplasty in the treatment of osteoporotic vertebrae compression fractures in the upper 1/3 of the vertebral body can effectively relieve pain,maintain vertebral height,and reduce operative time and bone cement leakage rate.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

BACKGROUND:Percutaneous curved vertebroplasty has the advantages of minimal trauma and bone cement dispersion,but whether it is safe and effective for the treatment of compression fractures in the upper 1/3 of the vertebral body needs further study.OBJECTIVE:To investigate the clinical efficacy of percutaneous curved vertebroplasty in the treatment of the upper 1/3 compression fractures of the osteoporotic vertebrae.METHODS:Medical records of 66 patients with osteoporotic thoracolumbar upper 1/3 compression fracture admitted to Department of Orthopedics of PLA Rocket Force Characteristic Medical Center from January 2020 to June 2023 were retrospectively analyzed.Among them,32 cases were treated with percutaneous curved vertebroplasty(observation group)and 34 cases were treated with"noncoplanar bipedicular puncture"percutaneous vertebroplasty(control group).Pain visual analog scale score,Oswestry Disability Index,anterior edge height of injured vertebra,and Cobb angle of injured vertebra were compared and analyzed between the two groups before surgery,the first day after surgery,and the last follow-up.The operative time,bone cement leakage rate,bone cement injection volume,and bone cement dispersion score of the two groups were statistically analyzed.RESULTS AND CONCLUSION:(1)The operations were successfully completed in both groups of patients,and no complications such as bone cement allergy,bone cement embolism,nerve damage,or epidural hematoma occurred.(2)Pain visual analog scale score,Oswestry disability index,anterior edge height,and Cobb angle of injured vertebra of the two groups at the first day after surgery and the last follow-up were all better than those before surgery,with statistically significant difference(P＜0.05),but there was no statistical significance between the two groups(P＞0.05).The Oswestry disability index of the two groups at the last follow-up was better than that on the first day after surgery(P＜0.05).(3)The operation time and bone cement leakage rate of the observation group were lower than those of the control group,and the differences were statistically significant(P＜0.05).(4)There were no significant differences in bone cement injection volume and bone cement dispersion score between the two groups(P＞0.05).(5)The results show that percutaneous curved vertebroplasty in the treatment of osteoporotic vertebrae compression fractures in the upper 1/3 of the vertebral body can effectively relieve pain,maintain vertebral height,and reduce operative time and bone cement leakage rate.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.

Objective To investigate the protective effect and mechanism of liraglutide on the paraquat (PQ)⁃ induced Parkinson's disease (PD) mouse model. Methods Totally 24 Kunming mice were randomly divided into control group, PQ group and PQ +liraglutide group, 8 mice in each group. PD model was established by intraperitoneal injection of PQ (10 mg/kg) for 5 consecutive days, and liraglutide (50 nmol/kg) was injected intraperitoneally for 7 consecutive days. The free⁃standing and locomotor activity of mice were measured by behavioral method. Immunofluorescence was used to observe the number of tyrosine hydroxylase (TH) and ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive cells. Western blotting was used to detect the expression of protein TH, glial fibrillary acidic protein (GFAP), mitofusin⁃2 (Mfn2) and dynamin⁃related protein 1 (Drp1). Results The numbers of free⁃standing and locomotor activity numbers decreased significantly (P<0.01, P < 0.05) in PQ group compared with the control group, and the number of TH immunoreactive cells and TH protein expression in substantia nigra decreased significantly (P<0.01, P<0.01) compared with the control group, while the number of Iba1 immunoreactive cells and GFAP protein expression increased significantly (P<0.01, P<0.01) compared with the control group; the expression of Drp1 protein in PQ group was significantly higher than that in control group (P<0.05), while the Mfn2 protein expression decreased significantly (P<0.05) compared with the control group. After treatment with liraglutide, the number of TH positive cells in PQ + liraglutide group was significantly lower than that in control group (P<0.05); the numbers of free⁃standing and locomotor activity increased significantly (P<0.05, P<0.05) in PQ + liraglutide group compared with the PQ group, and the number of TH positive cells and expression of TH protein in PQ + liraglutide group were significantly higher than that in PQ group (P<0.01, P< 0.01); while the number of Iba1 positive cells and GFAP protein expression decreased significantly (P<0.01, P<0.05) compared with the PQ group; the Drp1 protein expression decreased significantly (P<0.01) compared with the PQ group, while the expression of Mfn2 protein in PQ + liraglutide group was significantly higher than that in PQ group (P<0.01). Conclusion Liraglutide has neuroprotective effect by reducing neuroinflammation in substantia nigra, regulating mitochondrial fusion and fission.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.