Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

support the diagnosis.The treatment of PHCC is mainly based on surgery.Due to the characteristics of intact capsule,surgical resection is relatively easy and the cure rate is higher than that of ordinary hepatocellular carcinoma,and the postoperative survival rate is relatively ideal.For unresectable PHCC,palliative treatment based on transcatheter arterial chemoembolization can be used.This article reviews the progress on diagnosis and treatment of PHCC in order to provide reference for clinical practice.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Lung cancer is the leading cause of cancer-related deaths worldwide. Radiation pneumonitis is a major complication in lung cancer radiotherapy. Four-dimensional computed tomography (4DCT) imaging provides dynamic ventilation information, which is valuable for lung function assessment and radiation pneumonitis prevention. Many methods have been developed to calculate lung ventilation from 4DCT, but a systematic comparison is lacking. Prediction of radiation pneumonitis using 4DCT-based ventilation is still in an early stage, and no comprehensive review exists. This paper presented the first systematic comparison of functional lung ventilation algorithms based on 4DCT over the past 15 years, highlighting their clinical value and limitations. It then reviewed multimodal approaches combining 4DCT ventilation imaging, dose metrics, and clinical data for radiation pneumonitis prediction. Finally, it summarized current research and future directions of 4DCT in lung cancer radiotherapy, offering insights for clinical practice and further studies.
Humans ; Lung Neoplasms/diagnostic imaging* ; Four-Dimensional Computed Tomography/methods* ; Radiation Pneumonitis/etiology* ; Algorithms ; Lung/radiation effects* ; Pulmonary Ventilation

AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.

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