Objective:To investigate the impact of coronary angiography-derived index of microcirculatory resistance (caIMR) on the long-term prognosis of patients with coronary heart disease (CHD) undergoing elective percutaneous coronary intervention (PCI).Methods:The study was a retrospective cohort study conducted at a single centre. Patients who successfully underwent elective PCI with pre-and post-PCI caIMR measurements in Peking University First Hospital between August 2013 and December 2020 were included. Then patients were categorised into three groups based on pre-and post-PCI caIMR: post-PCI caIMR<25 U group, pre-PCI caIMR<25 U and post-PCI caIMR≥25 U group, and both pre-and post-PCI caIMR≥25 U group. Collected clinical data of patients, including comorbid diabetes mellitus.The primary endpoint was a composite endpoint, defined as a composite of all-cause death, non-fatal myocardial infarction, and any revascularisation. The association between caIMR-based groupings and clinical outcomes was analysed using Cox proportional hazards regression models.Results:A total of 625 patients who underwent successful elective PCI were included in the study, among whom 294 (47.0%) had stable angina. The age was (64.5±10.1) years, and 440 (70.4%) patients were male. Over a median follow-up of 3.69 (1.80, 5.80) years, 122 patients (19.5%) experienced composite endpoint events. Post-PCI caIMR≥25 U in combination with diabetes mellitus was associated with an increased risk of the composite endpoint compared to those with post-PCI caIMR<25 U and without diabetes mellitus (adjusted HR=2.13, 95% CI 1.17-3.88, P=0.014). In the combined analysis, compared with post-PCI caIMR<25 U group, those with both pre-and post-PCI caIMR≥25 U had higher risks of composite endpoint (adjusted HR=2.01, 95% CI 1.18-3.43, P=0.010) and any revascularisation (adjusted HR=2.12, 95% CI 1.17-3.84, P=0.013). The pre-PCI caIMR<25 U and post-PCI caIMR≥25 U group showed no statistically significant differences in any of the endpoints compared to post-PCI caIMR<25 U group. Conclusions:Integrated pre-and post-procedural assessment of caIMR may enhance risk stratification in patients with coronary heart disease. Persistent coronary microvascular dysfunction present both before and after PCI, as measured by caIMR, serves as an independent risk factor for adverse events in patients with coronary heart disease undergoing elective PCI.

Objective:To investigate the impact of coronary angiography-derived index of microcirculatory resistance (caIMR) on the long-term prognosis of patients with coronary heart disease (CHD) undergoing elective percutaneous coronary intervention (PCI).Methods:The study was a retrospective cohort study conducted at a single centre. Patients who successfully underwent elective PCI with pre-and post-PCI caIMR measurements in Peking University First Hospital between August 2013 and December 2020 were included. Then patients were categorised into three groups based on pre-and post-PCI caIMR: post-PCI caIMR<25 U group, pre-PCI caIMR<25 U and post-PCI caIMR≥25 U group, and both pre-and post-PCI caIMR≥25 U group. Collected clinical data of patients, including comorbid diabetes mellitus.The primary endpoint was a composite endpoint, defined as a composite of all-cause death, non-fatal myocardial infarction, and any revascularisation. The association between caIMR-based groupings and clinical outcomes was analysed using Cox proportional hazards regression models.Results:A total of 625 patients who underwent successful elective PCI were included in the study, among whom 294 (47.0%) had stable angina. The age was (64.5±10.1) years, and 440 (70.4%) patients were male. Over a median follow-up of 3.69 (1.80, 5.80) years, 122 patients (19.5%) experienced composite endpoint events. Post-PCI caIMR≥25 U in combination with diabetes mellitus was associated with an increased risk of the composite endpoint compared to those with post-PCI caIMR<25 U and without diabetes mellitus (adjusted HR=2.13, 95% CI 1.17-3.88, P=0.014). In the combined analysis, compared with post-PCI caIMR<25 U group, those with both pre-and post-PCI caIMR≥25 U had higher risks of composite endpoint (adjusted HR=2.01, 95% CI 1.18-3.43, P=0.010) and any revascularisation (adjusted HR=2.12, 95% CI 1.17-3.84, P=0.013). The pre-PCI caIMR<25 U and post-PCI caIMR≥25 U group showed no statistically significant differences in any of the endpoints compared to post-PCI caIMR<25 U group. Conclusions:Integrated pre-and post-procedural assessment of caIMR may enhance risk stratification in patients with coronary heart disease. Persistent coronary microvascular dysfunction present both before and after PCI, as measured by caIMR, serves as an independent risk factor for adverse events in patients with coronary heart disease undergoing elective PCI.

Objective To explore the role of TLR4/NF-kB signal pathway in rat nerve injury after traumatic brain injury coupled with seawater drowning.Methods A total of 96 male Sprague-Dawley rats were randomly divided into 3 groups:the sham surgery group(n =12),the traumatic brain injury (TBI) group(n =42) and the traumatic brain injury coupled with seawater drowning group (or the TBI + SWD group) (n =42).At the timepoints of 3,6,12,24,72 and 168 hours after the establishment of the TBI model,immunohistochemistry was used to detect the expression of TLR4 and NF-kB cells in the rat brain tissue.Real time PCR (rt-PCR) was applied to detect the expression levels of TLR4 and NF-kB mRNA in the hippocampus of the brain tissue,and enzyme-linked immunosorbent assay (ELISA) was employed to detect the content of TNF-α in the rat brain tissue.Results The number of TLR4 and NF-kB positive cells in the brain tissue of the TBI group and the TBI + searwater drowning group increased.The expressions of TLR4 and NF-kB mRNA in the hippocampus of the brain tissue of the TBI group and the TBI + SWD group significantly increased 3 hours after establishment of the TBI model.For the TBI group,the expressions of TLR4 and NF-kB were respectively (1.63 ±0.52) and (1.52 ±0.41),while in the the TBI + SWD group,the expressions of the above 2 substantce were respectively (4 1.87 ± 0.93) and (1.87 ± 0.93).At hour 24,the expression reached peak.For the TBI group,the expressions of TLR4 and NF-kB were respectively (49.61 ± 0.34) and (4.60 ± 0.51),while for the the TBI + SWD group,the expressions of the above 2 substantces were respectively (16.11 ±0.49) and (5.80 ± 0.52),then they decreased gradually.The expression levels of TNF-α in the TBI group and the TBI + SWD group were found to elevate 3 hours after establishment of the model.TNF-α expression level for the TBI group was (53.68 ± 1.48) ng/L),while the expression level of the same substance for the TBI + SWD group was (60.14 ± 2.06) ng/L.Wave peak appeared at hour 12,and the wave peak for the TBI group was (79.28 ± 2.46) ng/L,while for the TBI + SWD group,it displayed at (103.51 ± 5.53) ng/L.Conclusion Seawater drowning could aggravate nerve inflammatory response mediated by TLR4/NF-kB signal pathway,which might play an important role in the rat brain injury induced by trauma.

Objective To explore the role of TLR4/NF-kB signal pathway in rat nerve injury after traumatic brain injury coupled with seawater drowning.Methods A total of 96 male Sprague-Dawley rats were randomly divided into 3 groups:the sham surgery group(n =12),the traumatic brain injury (TBI) group(n =42) and the traumatic brain injury coupled with seawater drowning group (or the TBI + SWD group) (n =42).At the timepoints of 3,6,12,24,72 and 168 hours after the establishment of the TBI model,immunohistochemistry was used to detect the expression of TLR4 and NF-kB cells in the rat brain tissue.Real time PCR (rt-PCR) was applied to detect the expression levels of TLR4 and NF-kB mRNA in the hippocampus of the brain tissue,and enzyme-linked immunosorbent assay (ELISA) was employed to detect the content of TNF-α in the rat brain tissue.Results The number of TLR4 and NF-kB positive cells in the brain tissue of the TBI group and the TBI + searwater drowning group increased.The expressions of TLR4 and NF-kB mRNA in the hippocampus of the brain tissue of the TBI group and the TBI + SWD group significantly increased 3 hours after establishment of the TBI model.For the TBI group,the expressions of TLR4 and NF-kB were respectively (1.63 ±0.52) and (1.52 ±0.41),while in the the TBI + SWD group,the expressions of the above 2 substantce were respectively (4 1.87 ± 0.93) and (1.87 ± 0.93).At hour 24,the expression reached peak.For the TBI group,the expressions of TLR4 and NF-kB were respectively (49.61 ± 0.34) and (4.60 ± 0.51),while for the the TBI + SWD group,the expressions of the above 2 substantces were respectively (16.11 ±0.49) and (5.80 ± 0.52),then they decreased gradually.The expression levels of TNF-α in the TBI group and the TBI + SWD group were found to elevate 3 hours after establishment of the model.TNF-α expression level for the TBI group was (53.68 ± 1.48) ng/L),while the expression level of the same substance for the TBI + SWD group was (60.14 ± 2.06) ng/L.Wave peak appeared at hour 12,and the wave peak for the TBI group was (79.28 ± 2.46) ng/L,while for the TBI + SWD group,it displayed at (103.51 ± 5.53) ng/L.Conclusion Seawater drowning could aggravate nerve inflammatory response mediated by TLR4/NF-kB signal pathway,which might play an important role in the rat brain injury induced by trauma.

CAR-T cell therapy that targets surface antigens to kill tumor cells specifically has recently become another cornerstone in tumor immunotherapy. In this study, a lentiviral expression plasmid of CAR targeting human epidermal growth factor receptor 2 (HER2) was constructed by genetic engineering. The recombinant plasmid was co-transfected with other packaging plasmids into HEK293T cells by calcium phosphate precipitation to generate lenti-car, which are CAR lentiviral particles. HER2-specific CAR-T cells were obtained by transducing human peripheral blood mononuclear cells with lenti-car. Their specific inhibitory effects on HER2-positive and HER2-negative tumor cells were analyzed in vitro. The constructed CAR-T cells were specifically activated by HER2-expressing tumor cells as indicated by secretion of IFN-γ and IL-2. The inhibitory rate on HER2-positive SK-OV-3 cell line was (58.47±1.72)%, significantly higher than that on the mock-treated control group (P<0.05). The inhibitory rate on HER2-negative K562 cell lines was (11.74±2.37)%, which was not significantly different from that on the control group (P>0.05). Furthermore, when we transfected a HER2-expressing vector into K562, the inhibitory rate increased to (30.41±7.59)%, which was higher than that on HER2-negative K562 (P<0.05). Thus, the constructed second-generation HER2-specific CAR-T cells specifically suppressed growth of tumor cells overexpressing HER2 protein, suggesting that HER2-specific CAR-T cells might prove useful for immunotherapy of HER2-positive cancer.

Various genetic switches have been developed to let engineered cells perform designed functions. However, a sustained input is often needed to maintain the on/off state, which is energy-consuming and sensitive to perturbation. Therefore, we developed a set of transcriptional switches for cell states control that were constructed by the inversion effect of site-specific recombinases on terminators. Such a switch could respond to a pulse signal and maintain the new state by itself until the next input. With a bottom-up design principle, we first characterized the terminators and recombinases. Then the mutual interference was studied to select compatible pairs, which were used to achieve one-time and two-time state transitions. Finally, we constructed a biological seven-segment display as a demonstration to prove such switch's immense potential for application.
Recombinases ; metabolism

OBJECTIVETo study the signaling pathways associated with lipopolysaccharide (LPS)-induced inflammation in islet micro-endothelial cells (IMECs) and the mechanism of pravastatin intervention.

METHODSIMECs exposed to LPS, SB203580, pravastatin, or SB203580+pravastatin were examined for cell apoptosis with Hoechst staining and flow cytometry and for expression levels of total-p38, photophosphorylation-p38 (p-p38) and iNOS with Western blotting.

RESULTSThe apoptosis rate and expression levels of total-p38, p-p38, iNOS in IMECs all increased after LPS exposure. Pravastatin, SB203580, and their combination significantly attenuated LPS-induced enhancement of cell apoptosis and total-p38, p-p38, and iNOS expressions in IMECs.

CONCLUSIONLPS-induced inflammatory toxicity in IMECs is associated with the activation of P38MAPK and iNOS/NO signaling pathways. Pravastatin can inhibit these pathways and suppress the apoptosis and necrosis of IMECs to relieve the cell inflammatory injuries.

Animals ; Apoptosis ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; cytology ; Inflammation ; Islets of Langerhans ; blood supply ; MAP Kinase Signaling System ; drug effects ; Mice ; Nitric Oxide Synthase Type II ; metabolism ; Phosphorylation ; Pravastatin ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To investigate the features,prevention and treatment of complications of ultrasound-guided hepatic puncture biopsy.Methods One hundred and seventy-five cases underwent ultrasound-guided hepatic puncture biopsy were retrospectively analyzed.Results The incidence of complications was 16 cases (9.1%),including 5 cases with vasovagal episodes(2.9%),4 cases with ache which needed medicine treatment (2.2%),3 cases with hemorrhage in liver capsule(1.7%),3 cases with hypoglycemia(1.7%),1 case with serve hemorrhage in abdominal cavity(0.6%).Hemorrhage limited in liver capsule,vasovagal episodes,hypoglycemia and ache were relieved with corresponding treatments.One case with hemorrhage in abdominal cavity was handled with percutaneous microwave ablation therapy guided by contrast-enhanced ultrasound.Conclusions Ultrasound-guided hepatic puncture biopsy has good value and low complication.The most severe complication is hemorrhage,which can be handled with percutaneous microwave ablation therapy guided by contrast-enhanced ultrasound.

Objective To analyze and compare the ultrasound characteristics in different pathologic classifications of thyroid carcinoma.The ultrasound characteristics of thyroid carcinoma were investigated in order to determine the clinical diagnosis and clinical stasing of thyroid carcinoma.Methods In this study,407 cases of thyroid carcinoma were enlisted for ultrasonic typing of thyroid carcinoma according to the ultrasound features.The resuh was used for clinical staging of thyroid carcinoma. Results Combined ultrasound mediated clinical stage has a higher accuracy rate and specificity,its accuracy rate of T stage is 93.9%,for No stage is 86.1%,for N1a stage is 80%,for Nlb stage is 74.9%.Preoporative US detected 51.5% occult metastatic LN.Conclusion Ultrasound has a very important effectiveness for the evaluation.staging,location of thyroid carcinoma and cervical lymph node metastasis.