BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVE: Recent studies have overturned the traditional concept of the lung as a "sterile organ" revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis. METHODS: Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure. RESULTS: Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation. CONCLUSION Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
Animals ; Silicosis/prevention & control* ; Lung/metabolism* ; Mice ; Anti-Bacterial Agents/pharmacology* ; Microbiota/drug effects* ; Silicon Dioxide/toxicity* ; Mice, Inbred C57BL ; Male ; Pulmonary Surfactant-Associated Proteins/genetics*

Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong, has significant antithrombotic activity, but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear. In this paper, the main active components, potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro, network pharmacology analysis, molecular docking technology and molecular biology experiments. The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner. Using network pharmacology analysis, it was revealed that salvianolic acid B, tanshinone IIA, caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF), interleukin 6 (IL6) and AKT serine/threonine kinase 1 (AKT1). HMGB1 signaling pathway is one of its key common mechanisms. Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets. In summary, this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae. The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2023187g1549).

Objective A finite element simulation analysis of a bracketless orthodontic appliance was carried out to determine the correction amount under different working conditions.A design scheme for the bracketless orthodontic appliance was also formulated to create an orthodontic appliance formed by the fused deposition process with a personalized orthodontic effect.Methods Combined with the computed tomography data of the patient,a tooth model was reversely reconstructed.The correction amount of the tooth under tilting,twisting,and translation working conditions was established using the finite element method.Materials with different elastic moduli were chosen to make three-dimensional(3D)shaped bracketless orthodonitc appliance,and the orthodontic force was measured.Results Different correction amounts could be designed according to different working conditions so that the orthodontic appliance had a personalized treatment effect.The orthodontic force of the bracketless orthodontic appliance increased with elastic modulus and thickness.Under the given working conditions,the orthodontic force was minimal(90 mN)when the orthodontic material was at the minimum(90 mN).The orthodontic force reached its maximum value when the orthodontic material was at the maximum(61.66 N).Conclusions According to the patient's tooth condition and the size of the orthodontic force required for each step of correction in the whole correction process,the design should consider bracketless orthodontics with different elastic moduli and thicknesses to treat deformed teeth to realize the effect of staged orthodontic correction.

Objective To investigate the effect of continuous intraoperative insulin infusion on my-ocardial blood perfusion after cardiac surgery under cardiopulmonary bypass(CPB).Methods Forty-eight patients,21 males and 27 females,aged 55-80 years,BMI 18-28 kg/m2,ASA physical status Ⅱ-Ⅳ,who underwent elective cardiac surgery with CPB were selected and randomly divided into two groups:the insulin group(group I,n = 25)and the control group(group C,n = 23).The same anesthesia protocol was implemented in both groups.After induction of anesthesia,group Ⅰ received intravenously infusion of in-sulin 30 mU·kg-1·h-1,glucose 0.12 g·kg-1·h-1,and potassium chloride 0.06 mmol·kg-1·h-1,and group C received saline 10 ml/h,all of which were infused until the end of surgery.The targeted blood glucose range for both groups was set at 6.1-11.1 mmol/L.Transesophageal echocardiography(TEE)was performed 10 minutes after induction of general anesthesia(T2)and before the end of surgery(T6)to ex-amine the coronary sinus(CS)flow spectrum and diameter,pulmonary venous flow spectrum,and calculate CS net antegrade flow velocity time integral(VTI).Femoral mean arterial pressure(MAP),central venous pressure(CVP),stroke volume(SV),cardiac index(CI)and peripheral vascular resistance index(SVRI)were recorded at T2,2 minutes before CPB(T3),the end of CPB(T5),and T6.The concentra-tions of blood glucose and lactate 5 minutes before anesthesia induction(T1),T3,30 minutes after CPB(T4),T5,T6,6 hours after surgery(T7),12 hours after surgery(T8),and 24 hours after surgery(T9)were recorded.The levels of high-sensitivity C-reactive protein(hs-CRP),high-sensitivity troponin I(hs-TnI),and creatine kinase isoenzyme(CK-MB)were recorded 1 day preoperatively,1 and 2 days post-operatively.Results Compared with group C,in group I,CS net antegrade flow VTI and blood flow per minute were significantly increased(P<0.05),and pulmonary venous peak atrial reversal wave velocity(ARp)was significantly reduced at T6(P<0.05),SV and CI were significantly increased and SVRI was significantly decreased at T5 and T6(P<0.05),lactate concentration was significantly decreased at T7 and T8(P<0.05),hs-CRP and CKMB were significantly decreased 1 and 2 days postoperatively(P<0.05),hs-TnI was significantly reduced 2 days postoperatively(P<0.05).Conclusion Continuous insulin admin-istration during cardiac surgery with CPB while maintaining blood glucose at 6.1-11.1 mmol/L can enhance myocardial blood perfusion,mitigate postoperative inflammatory response,and reduce myocardial injury.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Animals ; Rats ; Explosions ; Proteomics ; Autophagy

Humans ; Infant ; Infant, Newborn ; Infant, Extremely Low Birth Weight ; Mesenchymal Stem Cell Transplantation ; Umbilical Cord/cytology* ; Skin/injuries*

Objective To evaluate the quality of postoperative recovery of patients undergoing cardiac great vessels surgery by 15-item Recovery Quality Score Scale(QoR-15),to retrospectively analyze the influence of perioperative multi-factors on postoperative recovery quality,and to establish the predictive model.Methods Clinical data of patients who underwent cardiac great vascularsur-gery from March 2020 to September 2022 were collected through electronic medical record system and the postoperative QoR-15 score were evaluated.The data including gender,age,postoperative follow-up time,American Society of Anesthesiologists(ASA)classification,preoperative lactate level,co-morbidities,emergency or not,extracorporeal circulation or not,etc.were collected.The modified frailty index(mFI)was also calculated.Surgical patterns,operation time,extracorporeal circulation time,aortic block time,type of heart recurrence,perioperative fluid therapy,extracorporeal circulation temperature,and other postoperative data as well as postoperative data including ICU retention time after surgery,total length of stay and QoR-15 score were recorded.The univariate and multivariate Logistic regression analysis were then applied to construct a prediction model,and its accuracy was validated.Results A total of 213 patients were included,in which 15 patients were excluded,and 198 postoperative QoR-15 score sheets were received.Gender,ASA classification,preoperative lac-tate level,postoperative follow-up time,and mFI were significant influencing factors on the quality of rehabilitation of patients undergoing cardiac or great vascular surgery.The prediction model of ln(p/1-p)=-5.571+0.862 × gender+3.844 × ASA classification+3.143 × preoperative lactate level+2.001 × postoperative follow-up time+3.712 × mFI,which had good predictive and classifi-cation effects.Conclusion Gender,ASA classification,preoperative lactate level,postoperative follow-up time and mFI are influencing factors on the recovery quality of patients after cardiac great vascular surgery.