The protective effect of niacinamide on interleukin-1beta (IL-1beta)-induced annulus fibrosus (AF) type II collagen degeneration in vitro and the mechanism were investigated. Chiba's intervertebral disc (IVD) culture models in rabbits were established and 48 IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups: normal control group, niacinamide-treated group, type II collagen degneration group (IL-1beta) and treatment group (niacinamide+IL-1beta). After culture for one week, AFs were collected for inducible nitric oxide synthase (iNOS), cysteine containing aspartate specific protease-3 (Caspase-3) and type II collagen immunohistochemical examination, and type II collagen reverse transcription polymerase chain reaction (RT-PCR). The results showed that rate of iNOS positive staining AF cells in the 4 groups was 17.6%, 10.9%, 73.9% and 19.3% respectively. The positive rate in treatment group was significantly lower than in the type II collagen degeneration group (P<0.01). Rate of Caspase-3 positive staining AF cells in the 4 groups was 3.4%, 4.2%, 17.6% and 10.3% respectively. The positive rate in treatment group was lower than in the type II collagen degeneration group (P<0.01). Type II collagen staining demonstrated that lamellar structure and continuity of collagen in treatment group was better reversed than in the degeneration group. RT-PCR revealed that the expression of type II collagen in treatment group was significantly stronger than that in type II collagen degeneration group (P<0.01). It was concluded that niacinamide could effectively inhibit IL-1beta stimulated increase of iNOS and Caspase-3 in AF, and alleviate IL-1beta-caused destruction and synthesis inhibition of type II collagen. Niacinamide is of potential for clinical treatment of IVD degeneration.

Objective: To evaluate the impact of intracoronary administration of eptifibatide oncoronary no-reflow and myocardium perfusion in patients with ST-elevation myocardial infarction (STEMI) at percutaneous coronary intervention (PCI). Methods: A total of 80 STEMI patients with emergent PCI were randomly divided into 2 groups: Eptifibatide group, the patients received intracoronary administration of eptiifbatide and Control group, the patients received the same volume of normal saline.n=40 in each group. The baseline condition, post-operative vascular recanalization, changes of platelet aggression at pre- and post-medication were compared between 2 groups. Echocardiography was examined at immediately and 24 weeks after operation;myocardial infusion imaging was examined at l week after operation. All patients were followed-up for 24 weeks to observe the incidence of major adverse cardiovascular events (MACE). Results: Compared with Control group, Eptifibatide group showed increased ratios of post-operative TIMI grade 3 (72.5%vs 92.5%) and myocardium perfusion (70.0% vs 90.0%), bothP<0.05; decreased post-operative and 2h post-medicinal platelet aggression and they were both lower than Control group at the same period, allP<0.05. Eptiifbatide group had obviously improved LVEDD and LVEF at 24-week than 1-week after PCI and they were both superior to Control group, allP<0.05. There were 7 (17.5%) patients in Eptiifbatide group and 7 (7.5%) in Control group suffering from small bleeding events, P>0.05; no severe bleeding eventand no in-hospital thrombocytopeniaoccurred. MACE occurrence rates during 24-week follow-up period were 12.5% vs 22.5%, P>0.05. Conclusion: Intracoronary administration of eptiifbatide in STEMI patients at emergent PCI could effectively improve coronary blood lfow,increase myocardium perfusion and enhance cardiac function without severe bleeding events.

Objective:To evaluate the relationship between the mechanism of promoting wound healing by modified autologous blood transfusion and metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) in diabetic mice. Methods:Twenty SPF ICR mice, weighing 21-25 g, in which the diabetic model was successfully established, were divided into 2 groups ( n=10 each) using a random number table method: modified preservation group (group I) and ordinary preservation group (group O). Peripheral venous blood samples were collected and stored in the corresponding preservation solution for 7 days.The platelet aggregation rate, blood glucose, serum glycosylated hemoglobin (GHB) and phosphodiesterase (DPG) concentrations and WBC were measured.Autologous blood was transfused back immediately after the wound model was established.The percentage of wound healing area was calculated at 7, 10 and 14 days after autologous blood transfusion.The expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, matrix metalloproteinase-9, β-actin, type Ⅰ collagen (Col Ⅰ), Col Ⅲ protein and mRNA and MALAT1 was determined by Western blot, immunohistochemistry and quantitative real-time polymerase chain reaction respectively, at 14 days after transfusion. Results:Compared with group O, the blood glucose, serum concentrations of GHB and DPG, and WBC were significantly decreased, platelet aggregation rate was increased, the percentage of wound healing area was increased, the positive staining rate of Col Ⅰ and Col Ⅲ was increased, and the expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, matrix metalloproteinase-9, ColⅠ, Col Ⅲ and β-actin protein and mRNA and MALAT1 was up-regulated in group I ( P<0.05). Conclusion:The mechanism by which modified autologous blood transfusion promotes wound healing may be related to up-regulating MALAT1 expression in diabetic mice.

The regulatory effects of niacinamide (Nia) on intervertebral disc (IVD) aggrecan in vitro was investigated. Chiba's 10 ng/mL interleukin-1 (IL-1)-induced rabbit IVD degeneration model in vitro was established. 0.5, 0.25 and 0.05 mg/mL Nia was added to normal and degenerated IVDs for intervention. On the first and second week after intervention, safranin O-fast green staining intensity and glycosaminoglycan (GS) content were measured. The expression of aggrecan core protein was detected by RT-PCR. The results showed: (1) After treatment with 0.5 mg/mL Nia for one week, the GS content in nucleus pulposus (NP) was increased by 44.8 % as compared with control group (P＜0.01); The GS content in IL-1 induction groups was increased with the increase of Nia concentrations: After treatment with 0.5 mg/mL for one week, the GS content in NP was increased by 68.3 % as compared with control group (P＜0.01). After two weeks, GS content in NP and fibrous rings was still higher than in control group at the same period (P＜0.01)and untreated group (P＜0.01). (2) Safranin O-fast green staining revealed that with the increase of Nia concentrations, staining density in NP and fibrous rings was increased and histological structure damage to IVDs by IL-1β was alleviated. (3) RT-PCR showed that the expression of core protein gene in IL-1β-induced degenerated IVDS was increased with the increase of Nia concentrations.It was concluded that under conditions in vitro, Nia could up-regulate the expression of aggrecan in IVDs and protect IVDs from IL-1β-induced degeneration at least partially, which offers a potential choice for IVD degeneration clinical therapy.

The protective effect of niacinamide on interleukin-1β (IL-1β)-induced annulus fibrosus (AF) type Ⅱ collagen degeneration in vitro and the mechanism were investigated. Chiba's intervertebrai disc (IVD) culture models in rabbits were established and 48 IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups: normal control group, niacinamide-treated group, type Ⅱ collagen degneration group (IL-1β) and treatment group (niacinamide+IL-1β). After culture for one week, AFs were collected for inducible nitric oxide synthase (iNOS), cysteine containing aspartate specific protease-3 (Caspase-3) and type Ⅱ collagen immunohistochemical examination, and type Ⅱ collagen reverse transcription polymerase chain reaction (RT-PCR). The results showed that rate of iNOS positive staining AF cells in the 4 groups was 17.6%, 10.9%, 73.9% and 19.3% respectively. The positive rate in treatment group was significantly lower than in the type Ⅱ collagen degeneration group (P＜0.01). Rate of Caspase-3 positive staining AF cells in the 4 groups was 3.4%, 4.2%, 17.6% and 10.3% respectively. The positive rate in treatment group was lower than in the type Ⅱ collagen degeneration group (P＜0.01). Type Ⅱ collagen staining demonstrated that lamellar structure and continuity of collagen in treatment group was better reversed than in the degeneration group. RT-PCR revealed that the expression of type Ⅱ collagen in treatment group was significantly stronger than that in type Ⅱ collagen degeneration group (P＜0.01). It was concluded that niacinamide could effectively inhibit IL-1β stimulated increase of iNOS and Caspase-3 in AF, and alleviate IL-1β-caused destruction and synthesis inhibition of type Ⅱ collagen. Niacinamide is of potential for clinical treatment of IVD degeneration.

OBJECTIVETo summarize the experience of minimally invasive treatment in 520 patients with intracranial aneurysms on a retrospective study.

METHODSThe measures used in the treatment of 520 patients were reviewed in terms of timing of surgery, induced-hypotensive anesthesia, brain protection combined with temporal occlusion of the feeding artery, external drainage of CSF, dynamic monitoring of intracranial pressure, blood flow velocity, serum osmolality and CT scanning, anti-vasospasm therapy as well as selected interventional endovascular embolization of aneurysms.

RESULTSOf the 520 patients, 485 were treated with either direct clipping or endovascular embolization and 35 patients were treated non-surgically. In 449 patients undergoing direct clipping and 36 undergoing endovascular embolization, intraoperative rupture of aneurysm occurred in 27 (6.0%) and 0%, respectively. Death occurred in 13 (2.6%), hemiplegia in 8 (1.6%), and vegetative state in 2 (0.4%). The operative mortality of direct clipping was 3.8% in 210 patients before 1990 and 1.8% in 275 patients after 1990 (36 patients undergoing endovascular embolization, the operative mortality was 0%).

CONCLUSIONThe outcome of patients with intacranial aneurysms can be markedly improved and the operative mortality can be lowered by minimally invasive treatment.

Adult ; Aneurysm, Ruptured ; mortality ; therapy ; Embolization, Therapeutic ; Female ; Follow-Up Studies ; Humans ; Intracranial Aneurysm ; mortality ; surgery ; Intraoperative Complications ; mortality ; Male ; Microsurgery ; Middle Aged ; Minimally Invasive Surgical Procedures ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Objective:To identify gene mutations in a family with incontinentia pigmenti, in order to confirm pathogenic mutations.Methods:Clinical data were collected from all patients in a family with incontinentia pigmenti. DNA was extracted from peripheral blood samples obtained from the patients, healthy members in the family, and 100 unrelated healthy controls, and Sanger sequencing was performed for all exons and their flanking sequences of the NEMO gene.Results:Totally, there were 4 patients in the 4-generation family, who all presented with typical skin lesions and different symptoms. Genetic testing indicated that the proband and the other 3 patients all carried a heterozygous nonsense mutation c.1153C>T (p.Gln385X) at position 1153 in exon 8 of the NEMO gene, which led to the substitution of the glutamine codon (CAG) by the termination codon (TAG) at amino acid position 385. The mutation was not identified in the 14 healthy relatives or 100 unrelated healthy controls. The mutation cosegregated with incontinentia pigmenti in the family. Database searching confirmed the mutation to be a novel nonsense mutation, and it was considered as a very strong pathogenic locus according to the American College of Medical Genetic and Genomics guidelines.Conclusion:The mutation c.1153C>T in the NEMO gene is associated with the occurrence of incontinentia pigmenti in this family.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

BACKGROUND:Bone defects can directly affect the success rate and long-term stability of dental implants.Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts,but less is reported on its pathways related to osteogenic differentiation. OBJECTIVE:To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments. METHODS:Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside(0.5,1,5,10,and 50 μmol/L)in promoting the proliferation and differentiation of MC3T3-E1 cells.There were four groups in the experiment:control group,salidroside group,salidroside+LY294002 group,and LY294002 group,which were cultured with osteogenic induction solution,osteogenic induction solution containing 10 μmol/L salidroside,osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002,and osteogenic induction solution containing 10 μmol/L LY294002,respectively.The effects of salidroside and LY294002,an inhibitor of the PI3K/Akt signaling pathway,on the expressions of genes and proteins related to osteogenesis were observed. RESULTS AND CONCLUSION:Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L.Compared with the control group,salidroside could promote mineralization,promote cell adhesion,reduce cell death,increase mRNA expression of Runx-2,osteocalcin and osteopontin(P<0.01),and increase protein expression of Runx-2 and p-Akt(P<0.01).However,the addition of LY294002 reversed the above results.These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins,which may be related to the activation of PI3K/Akt signaling pathway.

Objective To translate the Eating Behaviors Assessment for Obesity(EBA-O)and test its reliability and validity for providing an effective tool for brief and rapid clinical assessment of dietary behavior in obese patients.Methods The Chinese version of EBA-O was developed by Brislin's translation model for translation,back translation,cultural adaptation,and pilot investigation.Using convenience sampling method,200 obese patients who were admitted to the inpatient ward of the Weight Loss Center of a tertiary hospital in Beijing from April to June 2023 and planned to undergo weight loss metabolic surgery were selected as the research participants to test the reliability and validity of the Chinese version of EBA-O.Results The Chinese version of EBA-O includes 4 dimensions,with a total of 17 items.The Cronbach's α coefficient of the scale is 0.886;the Cronbach's αcoefficients of the dimensions are 0.770～0.866;the test-retest reliability of the scale is 0.881.The content validity index of the scale level is 0.980,and the content validity indexes of item level were 0.889～1.000.Totally 4 common factors were extracted through exploratory factor analysis,with a cumulative variance of 66.363％.Conclusion The Chinese version of EBA-O has good reliability and validity,and it can be used as a tool to evaluate the dietary behavior of obese patients undergoing weight loss metabolic surgery.