OBJECTIVETo investigate the inhibitory effects of antisense oligonucleotides to different sequences on VEGF gene expression by human hepatoma cells.

METHODSSMMC7721 cells were cultured under normoxic or hypoxic conditions for 24 h, followed by being transfected with different antisense oligonucleotides (A06513 to cap structure, A06514 to translation initiation, A06515 to Exon-3 and A06516 to translation terminal). The total RNAs from the cells were extracted and the VEGF expression were examined with RT-PCR. The relative concentrations of VEGF transcripts in SMMC772 cells from different groups were determined using GAPDH (glyceraldehyde-3-phosphate dehydrogenase) cDNA as internal standard.

RESULTSIn response to the hypoxic challenge, SMMC7721 cells upregulated VEGF mRNA; Comparative to the control (no oligonucleotides), A06513, A06514, A06515, and A06516 had obvious sequence-specific inhibitory effect on VEGF gene expression, with the ratio of VEGF over GAPDH of 0.49+/-0.08, 0.71+/-0.12, 0.72+/-0.11 and 0.86+/-0.12, respectively (F=12.21, P< 0.05). A06513 showed the strongest inhibitory effect (P<0.01).

CONCLUSIONThe antisense oligonucleotides complementary to VEGF cap structure, may become a potential alternative for antisense gene therapy of HCC.

Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; genetics ; therapy ; Oligonucleotides, Antisense ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors ; genetics

Objective To evaluate the clinical efficacy and safety of CT-guided percutaneous osteoplasty(POP)in the treatment of osteolytic metastases of the pelvis.Methods The clinical data of a total of 40 patients with pelvic osteolytic metastases,who received CT-guided POP at the Affiliated Zhongda Hospital of Southeast University between October 2011 and December 2021,were collected.Visual analogue scale(VAS)score was used to evaluate the clinical pain relief degree at one week,one month,3 months,6 months and 12 months after POP,and the joint function and the used dose of analgesic drugs were recorded.The preoperative and the postoperative 3-month,6-month and 12-month extents of the pelvic tumor destruction were compared.Based on the progression of local lesions within 12 months of follow-up,the patients were divided into controlled group and progression group.The proportion of using systemic anti-tumor therapy,the size of lesion,the amount of bone cement injected,and the cement filling ratio were compared between the two groups.Results Successful surgical procedure was accomplished for 57 lesions in 40 patients.The mean amount of bone cement injected was(4.56±2.25)mUpoint.In the 40 patients,the preoperative and the postoperative one-week,one-month and 3-month VAS score were(8.00±0.85)points,(2.05±0.96)points,(2.08±0.94)points and(2.18±0.84)points respectively,the difference in VAS score between preoperative value and postoperative one-week value was statistically significant(P＜0.01).In 37 patients,the postoperative 6-month VAS score was(2.35±0.54)points;and in 28 patients,the postoperative 12-month VAS score was(2.43±0.79)points.The differences in VAS score between postoperative one-week value and postoperative one-month,3-month,6-month,and 12-month values were not statistically significant(all P＞0.05),while the differences in VAS score between preoperative value and postoperative values were statistically significant(F=316.3,P＜0.01).The postoperative 3-month,6-month,and 12-month local control rates were 96.49％,85.19％,and 78.12％respectively,the differences between each other among the above three values were statistically significant(P=0.026).No statistically significant differences in the proportion of using systemic anti-tumor therapy,the lesion size and the amount of bone cement injected existed between the controlled group and the progression group(all P＞0.05).The cement filling ratio in the controlled group and the progression group was(81.26±9.17)％and(68.40±12.98)％respectively,and the difference between the two groups was statistically significant(P＜0.01).Conclusion For the treatment of pelvic metastases,CT-guided POP is clinically safe and effective.The injected bone cement can control the progression of local lesions for a longer time.(J Intervent Radiol,2023,32:1197-1201)

BACKGROUND AND PURPOSE: The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson's disease (PD) patients who experience fatigue. METHODS: PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins-α-synuclein oligomer, β-amyloid (Aβ)(1-42), and tau-were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients. RESULTS: The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of α-synuclein oligomer was higher and that of Aβ1-42 was lower in the fatigue group than in the non-fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the α-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders. CONCLUSIONS: PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased α-synuclein oligomer level in the CSF.
Anxiety ; Cerebrospinal Fluid ; Depression ; Fatigue* ; Humans ; Linear Models ; Parkinson Disease* ; Weights and Measures

OBJECTIVETo investigate the effect of HBP-A on meniscal injuries and the expressions of genes associated with pathological hypertrophy and calcification of the meniscusinduced by abnormal loading.

METHODSBovine meniscus explants were subjected to 25% strain at 0.3 Hz for 3 h and treated with 0.6 mg/mL of HBP-A. The cell viability in the meniscus explants after 72 hin culture was determined using live/dead staining and the expression levels of genes associated with pathological hypertrophy and calcification of the meniscus (ANKH, ENPP1, ALP, MMP13, and IL-1) were measured using real-time PCR and Western blotting. The conditioned medium was collected for testing sulfated glycosaminoglycan (GAG) release.

RESULTSThe number of dead cells, loss of proteoglycan content, and the expressions of ANKH, ENPP1, ALP and MMP13, and IL-1 at both the mRNA and protein levels were all significantly lower in the meniscus explants treated with 0.6 mg/mL HBP-A than in the explants with only 25% abnormal pressure stimulation (n=3, P<0.05).

CONCLUSIONHBP-A can effectively alleviate meniscal injuries induced by abnormal loading and suppress the expressions of genes related with pathological hypertrophy and calcification of the meniscus, and can serve as a potential drug for treatment of knee osteoarthritis.

Animals ; Calcinosis ; drug therapy ; Cattle ; Glucans ; pharmacology ; Hypertrophy ; Menisci, Tibial ; drug effects ; Osteoarthritis, Knee ; drug therapy ; Real-Time Polymerase Chain Reaction ; Tibial Meniscus Injuries ; drug therapy

Toxoplasmosis is a worldwide zoonosis caused by an intracellular protozoan parasite, Toxoplasma gondii. We report here a diabetic patient who was diagnosed as toxoplasmosis with multiple cranial nerve palsies and cavernous sinusitis. A 37-year-old male presented with an 11-day history of gingival pain, one day history of ptosis and diplopia. He has been having diabetes mellitus for 6 years, and has a history of contact with cats. After admission, his symptoms worsened with right 3rd to 7th cranial nerve palsies. The brain magnetic resonance imaging (MRI) showed cavernous sinusitis in the right sellar region. Serology for toxoplasma was positive for IgM and negative IgG. The patient was treated with oral clindamycin (900 mg/day) and dexamethasone (15 mg/day). The right visual acuity and lid-conjunctival swelling improved after 3 days. At follow-up after a month, the movement of the right eye significantly improved. This case demonstrate the rare occurrence of multiple cranial nerve (3rd to 7th) palsies from toxoplasmosis cavernous sinusitis, which is a potentially treatable condition.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*