BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:To investigate the current status and risk factors of central venous catheter-related thrombus（CRT）in critically ill children，and to provide evidence for proposing preventive measures.Methods:This study was a single-center cross-sectional survey.The hospitalized children with central venous catheters implanted in the intensive care unit of Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine from January to March 2024 were included.Based on the ultrasound diagnosis indicating CRT or the presence of visually detectable thrombi after central venous catheter removal,the children included in the study were categorized into the CRT group and the non-CRT group.The data of demographic，clinical data，laboratory tests，medication treatment，and catheter related information of the affected children were collected.Univariate and multivariate analyses were performed to identify risk factors associated with CRT.Results:A total of 328 children were included，of which 158 cases（48.2%）were female，with the median age of 35.00（9.00，88.75）months.There were 51 cases（15.6%）in CRT group and 277 cases（84.4%）in non-CRT group.After adjusted by pediatric critical illness score，multivariate binary Logistic analysis revealed that the use of normal saline for catheter flushing and sealing (adjust OR=26.52,95% CI 8.32-84.60, P<0.001),longer duration of vasoactive drug use (adjust OR=5.06,95% CI 1.93-13.26, P=0.001),higher Caprini scale score (adjust OR=3.09,95% CI 1.38-6.91, P=0.006),presence of high-risk comorbidities or complications (adjust OR=2.87,95% CI 1.11-7.45, P=0.030),longer immobilization time (adjust OR=1.13,95% CI 1.07-1.19, P<0.001),and lower international normalized ratio after catheter placement (adjust OR=0.10,95% CI 0.02-0.53, P=0.007) were independent risk factors affecting the occurrence of CRT. Conclusion:The incidence of CRT is relatively high among critically ill children,and medical staff can develop targeted intervention measures by taking relevant risk factors into consideration.

Objective To observe the correlation between cortical thickness and pathological deposition of β-amyloid(Aβ)in patients with Alzheimer disease(AD)induced mild cognitive impairment(MCI)or dementia.Methods Totally 22 AD patients were prospectively enrolled and divided into dementia group(n=12)and MCI group(n=10)based on the degree of cognitive impairment,while 17 healthy individuals without cognitive impairment were recruited as control group.MR examination and 18F-florbutaben(18F-FBB)PET imaging were performed,the cortical thickness and Aβ deposition value(Centiloid[CL]value)were calculated and compared among 3 groups and between each 2 groups,then the correlation between the above two indexes was analyzed.Results The cortical thickness in dementia group,MCI group and control group was(2.18±0.14),(2.35±0.08)and(2.36±0.09)mm,respectively,with significant difference among 3 groups(P＜0.05).The cortical thickness in dementia group was significantly thinner than that in MCI group and control group(both P＜0.05).CL value in dementia group,MCI group and control group was 77.97(63.07,95.55),65.51(54.54,90.50)and-1.17(-9.66,4.88),respectively,with significant difference among 3 groups(P＜0.05).CL value in dementia group and MCI group were significantly higher than in control group(both P＜0.05).The cortical thickness was moderately negatively correlated with CL value in MCI group(r=-0.580,P=0.048)but not in the other 2 groups(both P＞0.05).Conclusion The cortical thickness was moderately negatively correlated with abnormal deposition of Aβ in patients with AD induced MCI,but was not during dementia.

Objective To observe the correlation between cortical thickness and pathological deposition of β-amyloid(Aβ)in patients with Alzheimer disease(AD)induced mild cognitive impairment(MCI)or dementia.Methods Totally 22 AD patients were prospectively enrolled and divided into dementia group(n=12)and MCI group(n=10)based on the degree of cognitive impairment,while 17 healthy individuals without cognitive impairment were recruited as control group.MR examination and 18F-florbutaben(18F-FBB)PET imaging were performed,the cortical thickness and Aβ deposition value(Centiloid[CL]value)were calculated and compared among 3 groups and between each 2 groups,then the correlation between the above two indexes was analyzed.Results The cortical thickness in dementia group,MCI group and control group was(2.18±0.14),(2.35±0.08)and(2.36±0.09)mm,respectively,with significant difference among 3 groups(P＜0.05).The cortical thickness in dementia group was significantly thinner than that in MCI group and control group(both P＜0.05).CL value in dementia group,MCI group and control group was 77.97(63.07,95.55),65.51(54.54,90.50)and-1.17(-9.66,4.88),respectively,with significant difference among 3 groups(P＜0.05).CL value in dementia group and MCI group were significantly higher than in control group(both P＜0.05).The cortical thickness was moderately negatively correlated with CL value in MCI group(r=-0.580,P=0.048)but not in the other 2 groups(both P＞0.05).Conclusion The cortical thickness was moderately negatively correlated with abnormal deposition of Aβ in patients with AD induced MCI,but was not during dementia.

Objective:To investigate the current status and risk factors of central venous catheter-related thrombus（CRT）in critically ill children，and to provide evidence for proposing preventive measures.Methods:This study was a single-center cross-sectional survey.The hospitalized children with central venous catheters implanted in the intensive care unit of Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine from January to March 2024 were included.Based on the ultrasound diagnosis indicating CRT or the presence of visually detectable thrombi after central venous catheter removal,the children included in the study were categorized into the CRT group and the non-CRT group.The data of demographic，clinical data，laboratory tests，medication treatment，and catheter related information of the affected children were collected.Univariate and multivariate analyses were performed to identify risk factors associated with CRT.Results:A total of 328 children were included，of which 158 cases（48.2%）were female，with the median age of 35.00（9.00，88.75）months.There were 51 cases（15.6%）in CRT group and 277 cases（84.4%）in non-CRT group.After adjusted by pediatric critical illness score，multivariate binary Logistic analysis revealed that the use of normal saline for catheter flushing and sealing (adjust OR=26.52,95% CI 8.32-84.60, P<0.001),longer duration of vasoactive drug use (adjust OR=5.06,95% CI 1.93-13.26, P=0.001),higher Caprini scale score (adjust OR=3.09,95% CI 1.38-6.91, P=0.006),presence of high-risk comorbidities or complications (adjust OR=2.87,95% CI 1.11-7.45, P=0.030),longer immobilization time (adjust OR=1.13,95% CI 1.07-1.19, P<0.001),and lower international normalized ratio after catheter placement (adjust OR=0.10,95% CI 0.02-0.53, P=0.007) were independent risk factors affecting the occurrence of CRT. Conclusion:The incidence of CRT is relatively high among critically ill children,and medical staff can develop targeted intervention measures by taking relevant risk factors into consideration.

Objective To observe the effect of vacuum sealing drainage on the healing quality of cosmetic suture incision for large body surface masses.Methods From January 2020 to June 2023,60 patients with large surface mass hospitalized in the Department of Burns and Plastic Surgery of Northern Jiangsu People's Hospital were recruited as participants,and they were divided into study group and control group by block random method.Patients in the control group were treated with cosmetic suture technique to suture the surgical incision,while patients in the study group were treated with vacuum sealing drainage technique on the basis of cosmetic suture to further improve the quality of incision healing.The postoperative numerical rating scale(NRS)score,visual analogue scale(VAS)score,Vancouver Scar Scale(VSS)score,Patient Scar Assessment Scale(PSAS)score and other indicators were compared between the two groups.Results One week after surgery,the NRS score in the study group was(2.15±0.46)points,significantly lower than that in the control group(3.79±0.68)points,and the pain in the study group was less than that in the control group(P＜0.05).Two week after surgery,the VAS score in the study group(1.57±0.63)points was also lower than that in the control group(3.62±0.96)points(P＜0.05).The incision in the study group was smoother,and patients reported higher satisfaction with the incision compared to the control group.Six months post-operation,the VSS score in the study group(2.31±1.13)points was lower than that in the control group(3.49±1.46)points,while the PSAS score in the study group(7.68±1.65)points was significantly lower than that in the control group(11.33±1.92)points(P＜0.05).In the study group,the incision scar was lighter and the scar condition was better.Conclusion The application of vacuum sealing drainage technology in the cosmetic suture incision for large body surface masses can further improve the quality of incision healing,reduce incision scar,and improve patient satisfaction.

Objective To explore the effects of Buzhong Yiqi Decoction on PKCβ/Erk1/2/NF-κB signaling pathway in mice with autoimmune thyroiditis(AIT);To explore the mechanism of Buzhong Yiqi Decoction in the treatment of AIT.Methods Totally 808-week-old NOD.H-2h4 mice were randomly divided into control group,model group,TCM group and selenium yeast tablet group,with 20 mice in each group.The control group was fed with distilled water,and the other groups were given 0.05%sodium iodide for 8 weeks to establish AIT mice model.The medication groups were administered by gavage with corresponding drugs for 8 weeks.The morphology of thyroid tissue was detected by HE staining,ELISA was used to detected the contents of serum TGAb and TPOAb,RT-qPCR was used to detect the expression of PKCβ,Erk1/2,NF-κBp65,RORγt and IL-17 mRNA in thyroid tissue,the protein expressions of PKCβ,Erk1/2,NF-κBp65,RORγt and IL-17 in thyroid tissue were detected by Western blot.Results Compared with the control group,there were a large number of lymphocyte infiltration in thyroid tissue,and serum TGAb and TPOAb contents significantly increased(P<0.001),the expression of PKCβ,Erk1/2,NF-κBp65,RORγt and IL-17 mRNA and protein in thyroid tissue were significantly increased(P<0.001).Compared with the model group,the infiltration of lymphocytes in thyroid tissue of mice in TCM group and selenium yeast tablet group were alleviated,the contents of serum TGAb and TPOAb were significantly decreased(P<0.001),the mRNA and protein expressions of PKCβ,Erk1/2,NF-κBp65,RORγt and IL-17 in thyroid tissue were significantly decreased(P<0.001).There was no statistical significance in the indexes of TCM group and selenium yeast tablet group(P>0.05).Conclusion Buzhong Yiqi Decoction can regulate PKCβ/Erk1/2/NF-κB pathway,reduce inflammation in AIT mice and improve thyroid lymphocyte infiltration.

Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People＇s Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.