Individualized right ventricular outflow tract reconstruction using autologous pulmonary tissue in situ for the treatment of pulmonary atresia with ventricular septum defect.

OBJECTIVE: The study aims to evaluate the feasibility and effectiveness of an individualized procedure for right ventricular outflow tract (RVOT) reconstruction in pulmonary atresia with ventricular septal defect (PA-VSD). METHODS: RVOT was reconstructed using autologous pulmonary artery tissue preserved in situ as the posterior wall and a bovine jugular vein patch (BJVP) as the anterior wall in patients with PA-VSD (observation group). The size of the BJVP made from a bovine jugular vein conduit (BJVC) was individually calculated using a formula based on the child's weight and the size of the autologous pulmonary artery (the diameter of BJVC DB⁢J⁢V⁢C = Dt⁢h⁢e⁢o⁢r⁢e⁢t⁢i⁢c⁢a⁢l-W⁢z^-4π). Its effect was then compared with the conventional modified Rastelli procedure based on the BJVC (control group). RESULTS: A total of 22 patients that underwent the new procedure were simultaneously compared with the 25 patients in the control group. No deaths occurred in both groups. Notably, there were no significant differences in mechanical ventilation, ICU and postoperative residence, cardiopulmonary bypass, and aortic cross-clamp time. In the follow-up, which spanned for 8-12 years (mean 9.2 years), only four cases with moderate regurgitation were noted in the observation group without obstruction. In the control group, two patients had a conduit replacement. Three patients suffered from anastomotic stenosis, which was corrected by balloon dilatation. CONCLUSION: Individualized RVOT reconstruction with autologous pulmonary tissue preserved in situ as the posterior wall is adequate for treating PA-VSD.

Seismic evidence of negligible water carried below 400-km depth in subducting lithosphere.

Strong evidence exists that water is carried from the surface into the upper mantle by hydrous minerals in the uppermost 10-12 km of subducting lithosphere, and more water may be added as the lithosphere bends and goes downwards. Significant amounts of that water are released as the lithosphere heats up, triggering earthquakes and fluxing arc volcanism. In addition, there is experimental evidence for high solubility of water in olivine, the most abundant mineral in the upper mantle, for even higher solubility in olivine's high-pressure polymorphs, wadsleyite and ringwoodite, and for the existence of dense hydrous magnesium silicates that potentially could carry water well into the lower mantle (deeper than 1,000 km). Here we compare experimental and seismic evidence to test whether patterns of seismicity and the stabilities of these potentially relevant hydrous phases are consistent with a wet lithosphere. We show that there is nearly a one-to-one correlation between dehydration of minerals and seismicity at depths less than about 250 km, and conclude that the dehydration of minerals is the trigger of instability that leads to seismicity. At greater depths, however, we find no correlation between occurrences of earthquakes and depths where breakdown of hydrous phases is expected. Lastly, we note that there is compelling evidence for the existence of metastable olivine (which, if present, can explain the distribution of deep-focus earthquakes) west of and within the subducting Tonga slab and also in three other subduction zones, despite metastable olivine being incompatible with even extremely small amounts of water (of the order of 100 p.p.m. by weight). We conclude that subducting slabs are essentially dry at depths below 400 km and thus do not provide a pathway for significant amounts of water to enter the mantle transition zone or the lower mantle.

Individualized Analysis and Treatment of Difficult Weaning From Ventilation Following Open Cardiac Surgery in Young Children With Congenital Heart Disease.

Aims: The study explores the leading causes of postoperative extubation difficulties in pediatric patients (neonates and toddlers) with congenital heart diseases and establishes individualized treatment for different reasons. Method: We retrospectively analyzed medical records of 4,971 pediatric patients with congenital heart defects treated in three tertiary Congenital Heart Disease Centres in China from January 2005 to December 2020, from whom we selected those with difficulty extubation but successful weaning during the postoperative period. Next, we performed an analysis of risk factors and reported the combined experience of individualized treatment for successful extubation. Results: Seventy-five pediatric patients were identified in our database, among whom 23 had airway stenosis, 17 had diaphragmatic dysfunction, and 35 had pulmonary infection. The patients were all successfully weaned from the ventilator after an individualized treatment plan. In addition, the intubation time in the airway stenosis group was 17.7 ± 9.0, 33.6 ± 13.9 days in the diaphragmatic dysfunction group, and 11.9 ± 3.8 days in the pulmonary infection group. Conclusion: Given the primary reasons for difficult weaning following open-heart surgery in pediatric patients with congenital heart diseases, an individualized treatment scheme can achieve the ideal therapeutic effect where patients can be weaned faster with a shorter intubation period.

Cardiac Fibroblasts and Myocardial Regeneration.

The billions of cardiomyocytes lost to acute myocardial infarction (MI) cannot be replaced by the limited regenerative capacity of adult mammalian hearts, and despite decades of research, there are still no clinically effective therapies for remuscularizing and restoring damaged myocardial tissue. Although the majority of the cardiac mass is composed of cardiomyocytes, cardiac fibroblasts (CFs) are one type of most numerous cells in the heart and the primary drivers of fibrosis, which prevents ventricular rupture immediately after MI but the fibrotic scar expansion and LV dilatation can eventually lead to heart failure. However, embryonic CFs produce cytokines that can activate proliferation in cultured cardiomyocytes, and the structural proteins produced by CFs may regulate cardiomyocyte cell-cycle activity by modulating the stiffness of the extracellular matrix (ECM). CFs can also be used to generate induced-pluripotent stem cells and induced cardiac progenitor cells, both of which can differentiate into cardiomyocytes and vascular cells, but cardiomyocytes appear to be more readily differentiated from iPSCs that have been reprogrammed from CFs than from other cell types. Furthermore, the results from recent studies suggest that cultured CFs, as well as the CFs present in infarcted hearts, can be reprogrammed directly into cardiomyocytes. This finding is very exciting as should we be able to successfully increase the efficiency of this reprogramming, we could remuscularize the injured ventricle and restore the LV function without need the transplantation of cells or cell products. This review summarizes the role of CFs in the innate response to MI and how their phenotypic plasticity and involvement in ECM production might be manipulated to improve cardiac performance in injured hearts.

miR-199a Overexpression Enhances the Potency of Human Induced-Pluripotent Stem-Cell-Derived Cardiomyocytes for Myocardial Repair.

Mammalian cardiomyocytes exit the cell cycle during the perinatal period, and although cardiomyocytes differentiated from human induced-pluripotent stem cells (hiPSC-CMs) are phenotypically immature, their intrinsic cell-cycle activity remains limited. Thus, neither endogenous cardiomyocytes nor the small number of transplanted hiPSC-CMs that are engrafted by infarcted hearts can remuscularize the myocardial scar. microRNAs are key regulators of cardiomyocyte proliferation, and when adeno-associated viruses coding for microRNA-199a (miR-199a) expression were injected directly into infarcted pig hearts, measures of cardiac function and fibrosis significantly improved, but the treatment was also associated with lethal arrhythmia. For the studies reported here, the same vector (AAV6-miR-199a) was transduced into hiPSC-CMs, and the cells were subsequently evaluated in a mouse model of myocardial infarction. AAV6-mediated miR-199a overexpression increased proliferation in both cultured and transplanted hiPSC-CMs, and measures of left ventricular ejection fraction, fractional shortening, and scar size were significantly better in mice treated with miR-199a-overexpressing hiPSC-CMs than with hiPSC-CMs that had been transduced with a control vector. Furthermore, although this investigation was not designed to characterize the safety of transplanted AAV6-miR-199a-transduced hiPSC-CMs, there was no evidence of sudden death. Collectively, these results support future investigations of miR-199a-overexpressing hiPSC-CMs in large animals.

TT-10-loaded nanoparticles promote cardiomyocyte proliferation and cardiac repair in a mouse model of myocardial infarction.

The meager regenerative capacity of adult mammalian hearts appears to be driven by the proliferation of endogenous cardiomyocytes; thus, strategies targeting mechanisms of cardiomyocyte cell cycle regulation, such as the Hippo/Yes-associated protein (Hippo/Yap) pathway, could lead to the development of promising therapies for heart disease. The pharmacological product TT-10 increases cardiomyocyte proliferation by upregulating nuclear Yap levels. When intraperitoneal injections of TT-10 were administered to infarcted mouse hearts, the treatment promoted cardiomyocyte proliferation and was associated with declines in infarct size 1 week after administration, but cardiac function worsened at later time points. Here, we investigated whether encapsulating TT-10 into poly-lactic-co-glycolic acid nanoparticles (NPs) before administration could extend the duration of TT-10 delivery and improve the potency of TT-10 for myocardial repair. TT-10 was released from the TT-10-loaded NPs for up to 4 weeks in vitro, and intramyocardial injections of TT-10-delivered NPs stably improved cardiac function from week 1 to week 4 after administration to infarcted mouse hearts. TT-10-delivered NP treatment was also associated with significantly smaller infarcts at week 4, with increases in cardiomyocyte proliferation and nuclear Yap abundance and with declines in cardiomyocyte apoptosis. Thus, NP-mediated delivery appears to enhance both the potency and durability of TT-10 treatment for myocardial repair.

Individualized Surgical Reconstruction of the Right Ventricle Outflow Tract in Double Outlet Right Ventricle With Mirror Image-Dextrocardia.

Introduction: The purpose of this study was to report our experience in the surgical reconstruction of the right ventricular outflow tract in double outlet right ventricle with a major coronary artery crossing the right ventricular outflow tract in the presence of mirror image-dextrocardia. Methods: From January 2005 to December 2019, 19 double outlet right ventricle patients (median age 4 years) with mirror image-dextrocardia and a major coronary artery crossing the right ventricular outflow tract received surgical repair. An autologous pericardial patch was used to enlarge the right ventricular outflow tract in four patients without pulmonary stenosis and three patients with mild pulmonary stenosis. A valved bovine jugular venous conduit was added to a hypoplastic native pathway in nine patients, among which six patients with moderate pulmonary stenosis received small-sized bovine jugular venous conduit implantation (diameter ≤ 16 mm). In comparison, a large-sized bovine jugular venous conduit (diameter >16 mm) was adopted in a total of three patients with severe pulmonary stenosis. Finally, three patients with preoperative pulmonary hypertension (mean pulmonary artery pressure ≥40 mmHg) did not undergo further intervention of right ventricular outflow tract due to the adequate outflow tract blood flow. Results: There was no hospital mortality. One patient with sub-pulmonary ventricular septal defect and concomitant severe pulmonary hypertension died from respiratory failure 11 months after the operation. Kaplan-Meier survival was 94% at 5, 10 years. Within a mean echocardiographic follow-up of 6.9 ± 3.6 years, a total of two patients received reintervention due to valvular stenosis of the bovine jugular venous conduit (pressure gradient > 50 mmHg at 4 and 9 years) after surgical operation. Actuarial freedom from reoperation was 90 and 72% at 5 and 10 years, respectively. During the last echocardiographic follow-up phase, all the survivors were in NYHA class I. Conclusions: Double outlet right ventricle with mirror image-dextrocardia is a rare and complicated congenital cardiac malformation. Surgical reconstruction of the right ventricular outflow tract should be individualized based on the degree of pulmonary stenosis and the specific anatomical features of each patient. Reconstructing the pulmonary artery using the various sizes of valved bovine jugular venous conduit is a safe and effective surgical method.

TMSB4 Overexpression Enhances the Potency of Marrow Mesenchymal Stromal Cells for Myocardial Repair.

OBJECTIVE: The actin-sequestering proteins, thymosin beta-4 (Tß4) and hypoxia-inducible factor (HIF)-1α, are known to be associated with angiogenesis after myocardial infarction (MI). Herein, we aimed to identify the mechanism of HIF-1α induction by Tß4 and investigate the effects of bone marrow mesenchymal stromal cells (BMMSCs) transfected with the Tß4 gene (TMSB4) in a rat model of MI. METHODS: Rat BMMSCs were isolated, cultured, and transfected with the TMSB4 gene by using the lentivirus-mediated method. Rats with surgically induced MI were randomly divided into three groups (n = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 O E ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 W T ), or medium (MI). The fourth group of animals (n = 9) underwent all surgical procedures necessary for MI induction except for the ligation step (Sham). Four weeks after the injection, heart function was measured using transthoracic echocardiography. Infarct size was calculated by TTC staining, and collagen volume was measured by Masson staining. Angiogenesis in the infarcted heart area was evaluated by CD31 immunofluorescence histochemistry. In vitro experiments were carried out to observe the effect of exogenous Tß4 on HIF-1α and explore the various possible mechanism(s). RESULTS: In vivo experiments showed that vascular density 4 weeks after treatment was about twofold higher in BMMSC-TMSB4 O E -treated animals than in BMMSC-TMSB4 W T -treated animals (p < 0.05). The cardiac function and infarct size significantly improved in both cell-treatment groups compared to controls. Notably, the cardiac function and infarct size were most prominent in BMMSC-TMSB4 O E -treated animals (both p < 0.05). HIF-1α and phosphorylated HIF-1α (p-HIF-1α) in vitro were significantly enhanced by exogenous Tß4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1). The expression of prolyl hydroxylase domain proteins (PHD) was decreased upon treatment with Tß4 and further decreased with the combined treatment of Tß4 and FG-4497 (a specific PHD inhibitor). CONCLUSION: TMSB4-transfected BMMSCs might significantly improve recovery from myocardial ischemia and promote the generation of HIF-1α and p-HIF-1α via the AKT pathway, and inhibit the degradation of HIF-1α via the PHD and FIH pathways.

Clinical Application of Individualized Pulmonary Bi-Orifice for the Reconstruction of Right Ventricular Outflow Tract in Tetralogy of Fallot.

Objective: The study aims to establish a new method in the Tetralogy of Fallot (ToF) called the pulmonary valve bi-orifice method (pulmonary annular sparing with an individualized autologous pericardial patch; thus, two orifices are formed at the level of the pulmonary valve annulus) to reconstruct the right ventricular outflow tract (RVOT). Methods: A retrospective analysis of 128 TOF patients from October 2009 to June 2018 with severe pulmonary valve dysplasia who underwent transvalvular annular patch (TAP) procedure (control group) or an individualized pulmonary valve bi-orifice procedure (observation group) were studied. The RVOT for each patient in the observation group was individually reconstructed per the patient's weight and the size of the autologous pulmonary valve using the bi-orifice method; however, increasing the cross-sectional area of the pulmonary valve annulus without destroying its integrity. The result was then compared to the control group, where TAP procedures were applied to evaluate the short to mid-term outcome(s). An in vitro simulation test was used to verify the anti-regurgitation mechanism of the new method. Results: The in vitro simulation test indicated that the anti-regurgitation mechanism was completed by the pericardial patch and the autologous pulmonary valve movement toward each other. Thus, for clinical applications, patients in both groups were compared. The results showed no significant differences in cardiopulmonary bypass and aortic cross-clamp time, mechanical ventilation, and ICU and post-operative residence between the two groups. During the follow-up period (3- to 12-years), 14 patients in the observation group had mild regurgitation after surgery (22.2%), while 10 patients had moderate pulmonary regurgitation (15.8%) with no right ventricular (RV) dilation. On the other hand, 22 patients (39.6%) had moderate to severe regurgitation in the control group, while left pulmonary artery stenosis occurred in one patient. In the control group, six patients (9.2%) with severe RV dilation were reoperated. Conclusion: Individualized pulmonary valve bi-orifice procedure is a safe and excellent method for reconstructing RVOT in ToF.

Visualization and Identification of Bioorthogonally Labeled Exosome Proteins Following Systemic Administration in Mice.

Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an in vivo model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the non-canonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS∗) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes and resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS∗-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.

Endomyocardial fibrosis.

BACKGROUND: Endomyocardial fibrosis (EMF) is a neglected cardiovascular disease of poverty which carries a poor prognosis with no specific treatment affecting mainly children and young adults. Here, we report our 10-year experience in the therapeutic management and surgical treatment for EMF. METHODS: From February 2009 to 2019 March, 55 patients diagnosed with EMF from our cardiology unit underwent surgical repair at our department's pediatric surgical division. There were 35 male, and 20 female patients whose ages varied from 1 year 2 months to 12 years mean age 5.7 (±3.2). We designed the study aimed at assessing the cardio-structural abnormalities and coronary vascular changes faced with EMF patients using echocardiography, and coronary angiography with a detailed and thorough surgical examination of each case. RESULTS: Of the 55 operated patients, 1 had mild lesions, 26 had moderate lesions, and 28 had severe heart disease. All but one patient was in NYHA functional class III or IV at the time of surgery. All but one female patient with mild ventricular lesions and no valvular involvement had severe atrioventricular valve regurgitation with valves considered suitable for both replacements; 45 patients mean age 6.0 (±3.1) and repair nine patients mean age 3.8 (±2.9). The mean endocardial thickness was 3,000 (±1519) µm. CONCLUSIONS: The echocardiographic changes corresponded well to the findings on surgery and histopathology. The coronary changes seen included a spectrum of fibrin deposition, medial sclerosis and degeneration, and the formation of plexiform lesions. Surgically evaluating the resected cardiac tissue might help improve disease management.

Evaluating the cost-effectiveness of catheter ablation of atrial fibrillation.

BACKGROUND: The pursuit of a clearer understanding of the pathogenesis of atrial fibrillation (AFib) and the development of new technology has resulted in a surge of interest in the surgical ablation for AFib. Here, we report our 8-year experience in the surgical treatment and management of AFib alongside, evaluating the cost-effectiveness in southern Mainland China over a 1-year follow-up. METHODS: Data of 3,068 patients from March 2011 through June 2019 was retrospectively extracted from The Provincial National Cardiac Database of Xiangya Second Hospital. The activities considered (and costs calculated) were outpatient consultations, hospital admissions, and drug treatment. Quality of life (QoL) questionnaires were also carried out to assess whether concomitant AFib correction procedures increase risk in patients, or improve patient's QoL. RESULTS: A total of 3,068 patients completed the questionnaires at a minimum of one time-point during the follow-up. The total cost was combined to obtain incremental costs per quality-adjusted life-years (QALYs). The total costs of the AFib catheter ablation group were remarkably higher compared to surgery as usual group. The incremental cost-effectiveness ratio was $76,513,227 (¥542,287,667) per QALY, with an acceptability line graph for cost at 43%. CONCLUSIONS: AFib is an extraordinarily costly and worrisome public health problem. Precision medicine is vital as it provides a platform for the clinical translation of targeted interventions that are designed to help treat and prevent AFib. Thus, to improve the QoL expectancy outcome(s), both therapeutic and surgical interventions should be aimed at addressing the underlying heart disease rather than restoring sinus rhythm.

Application of Modified Sliding Anastomosis in the Repair of Aortic Coarctation.

OBJECTIVES: To evaluate the early and midterm results of a modified sliding anastomosis technique in patients with aortic coarctation. MATERIALS AND METHODS: In this study, we reported a new repair method and compared the early and midterm outcome(s) with a conventional surgical approach for the management of patients with aortic coarctation. Forty-eight aortic coarctation patients with a narrowed segment length longer than 2 cm were operated at our department's pediatric surgical division. Excision of the coarctation and end-to-end anastomosis was carried out in twenty-five patients (control group). In contrast, a modified sliding technique was used for twenty-three cases in the observation group. Other accompanying cardiac anomalies simultaneously repaired included ventricular septal defect and patent ductus arteriosus. All patients received 1.5-10 years of postoperative echocardiographic follow-up. RESULTS: This is a retrospective study carried out between January 2005 and June 2018. The study population consisted of forty-eight patients, which included twenty-six male and twenty-two female patients, with an average age of 5.2 ± 1.9 months (range, 28 days to 1 year). There was no mortality. The operative time, the number of intercostal artery disconnection, the drainage volume, and arm-leg systolic pressure gradient postoperation were less in the observation group as compared to the control group (p < 0.05). Also, cases with an anastomotic pressure gradient exceeding 10 mmHg during follow-up were less in the observation group as compared to the control group (p < 0.05). The postoperative complications encountered were chylothorax (control group 2 cases vs. observation group 0) and pulmonary atelectasis (control group 4 cases vs. observation group 1). They all, however, recovered after conservative treatment. Three patients in the control group underwent balloon angioplasty (reintervention) postoperative 2-4 years due to an increase in the anastomotic pressure gradient (>20 mmHg). After reintervention, the anastomotic pressure gradient reduced to 14 mmHg, 15 mmHg, and 17 mmHg, respectively. CONCLUSIONS: For long segment aortic coarctation patients (longer than 2 cm), the use of the modified sliding anastomotic technique effectively helps to retain more autologous tissues, enlarge the diameter of the anastomosis, and decrease anastomotic tension and vascular injury. Therefore, this technique provides a new idea for the surgical treatment of aortic coarctations.

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity.

Platelets are derived from megakaryocytes and play an important role in blood coagulation. By using high throughput sequencing, we have found that the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) is abundant in platelets (GEO ID: 200097348). However, little is known about its role in regulating megakaryocyte differentiation and platelet activity. This study aims to clarify the effect of NEAT1 on MEG-01 differentiation and platelet-like particle (PLP) activity. NEAT1 in MEG-01 cells was knocked down by siRNA transfection. The adhesion of MEG-01 and PLP to collagen-coated coverslips was observed under a fluorescence microscope. Flow cytometry was used to investigate cell apoptosis, cell cycle, the levels of D41/CD42b on MEG-01 cells and CD62P on PLPs. Quantitative real-time polymerase chain reaction was used to detect NEAT1 and IL-8 expression levels. Western blot was used to measure the protein levels of Bcl-2, Bax, cleaved caspase-3, and IL-8. RNA-binding protein immunoprecipitation was used to detect the interaction of NEAT1 and splicing factor proline/glutamine-rich (SFPQ). Results showed that NEAT1 knockdown decreased the adhesion ability of thrombin-stimulated MEG-01 and PLP. The expression of CD62P on PLPs and CD41/CD42b on MEG-01 cells was inhibited by NEAT1 knockdown. In addition, NEAT1 knockdown inhibited cell apoptosis with increased Bcl2/Bax ratio and decreased cleaved caspase-3, and reduced the percentage of cells in the G0/G1 phase. Meanwhile, NEAT1 knockdown inhibited the expression of IL-8. A strong interaction of NEAT1 and SFPQ, a transcriptional repressor of IL-8, was identified. NEAT1 knockdown reduced the interaction between SFPQ and NEAT1.The results suggest that lncRNA NEAT1 knockdown decreases MEG-01 differentiation, PLP activity, and IL-8 level. The results also indicate that the regulation of NEAT1 on IL-8 may be realized via a direct interaction between NEAT1 and SFPQ.

Earthquakes beneath the Himalayas and Tibet: evidence for strong lithospheric mantle.

Eleven intracontinental earthquakes, with magnitudes ranging from 4.9 to 6, occurred in the mantle beneath the western Himalayan syntaxis, the western Kunlun Mountains, and southern Tibet (near Xigaze) between 1963 and 1999. High-resolution seismic waveforms show that some focal depths exceeded 100 kilometers, indicating that these earthquakes occurred in the mantle portion of the lithosphere, even though the crust has been thickened there. The occurrence of earthquakes in the mantle beneath continental regions where the subduction of oceanic lithosphere ceased tens of millions years ago indicates that the mantle lithosphere is sufficiently strong to accumulate elastic strain.