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The indications for percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) are painful vertebral compression fractures. Our study is to assess the risk–benefit ratio of PKP/PVP surgery in the patients with newly diagnosed multiple myeloma (NDMM) without receiving antimyeloma therapy. The clinical data of 426 consecutive patients with NDMM admitted to our center from February 2012 to April 2022 were retrospectively analyzed. The baseline data, postoperative pain relief, the proportion of recurrent vertebral fractures, and survival time were compared between the PKP/PVP surgical group and the nonsurgical group in the NDMM patients. Of the 426 patients with NDMM, 206 patients had vertebral fractures (206/426, 48.4%). Of these, 32 (32/206, 15.5%) underwent PKP/PVP surgery for misdiagnosis of simple osteoporosis prior to diagnosis of MM (surgical group), and the other 174 (174/206, 84.5%) did not undergo surgical treatment prior to definitive diagnosis of MM (non-surgical group). The median age of patients in the surgical and nonsurgical groups was 66 and 62 years, respectively (p = 0.01). The proportion of patients with advanced ISS and RISS stages was higher in the surgical group (ISS stage II + III 96.9% vs. 71.8%, p = 0.03; RISS stage III 96.9% vs. 71%, p = 0.01). Postoperatively, 10 patients (31.3%) never experienced pain relief and 20 patients (62.5%) experienced short-term pain relief with a median duration of relief of 2.6 months (0.2–24.1 months). Postoperative fractures of vertebrae other than the surgical site occurred in 24 patients (75%) in the surgical group, with a median time of 4.4 months postoperatively (0.4–86.8 months). Vertebral fractures other than the fracture site at the first visit occurred in 5 patients (2.9%) in the nonoperative group at the time of diagnosis of MM, with a median time of 11.9 months after the first visit (3.5–12.6 months). The incidence of secondary fractures was significantly higher in the surgical group than in the nonsurgical group (75% vs. 2.9%, p = 0.001). The time interval between the first visit and definitive diagnosis of MM was longer in the surgical group than in the nonsurgical group (6.1 months vs. 1.6 months, p = 0.01). At a median follow-up of 32 months (0.3–123 months), median overall survival (OS) was significantly shorter in the surgical group than in the nonsurgical group (48.2 months vs. 66 months, p = 0.04). Application of PKP/PVP surgery for pain relief in NDMM patients without antimyeloma therapy has a limited effect and a high risk of new vertebral fractures after surgery. Therefore, patients with NDMM may need to have their disease controlled with antimyeloma therapy prior to any consideration for PKP/PVP surgery.

The structural characteristics and immunoregulatory activities of neutral heteropolysaccharide (AVRP-N) separated from the roots of Apocynum venetum L. were extensively investigated. The results showed that the weight average molecular mass (Mw) of AVRP-N was 6.430 × 10

The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high-dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world.We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real-world setting. Patients were divided into three groups according to induction regimens.The median age of the cohort was 70 (65-86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow-up of the cohort was 30 (interquartile range [IQR] 18-36) months. For the entire cohort median progression-free survival (PFS) was 26 (IQR 12.00-42.89) months and overall survival (OS) was 60 (IQR 40.00-67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age70 year, frailty status (Geriatric vulnerability score), induction efficacy partial remission, and no maintenance treatment were independent poor prognostic factors for OS.Front-line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real-world setting.

Obesity, dyslipidemia and gut dysbiosis are all linked to cardiovascular diseases. A Ganoderma meroterpene derivative (GMD) has been shown to alleviate obesity and hyperlipidemia through modulating the gut microbiota in obese mice. Here we show that GMD protects against obesity-associated atherosclerosis by increasing the abundance of Parabacteroides merdae in the gut and enhancing branched-chain amino acid (BCAA) catabolism. Administration of live P. merdae to high-fat-diet-fed ApoE-null male mice reduces atherosclerotic lesions and enhances intestinal BCAA degradation. The degradation of BCAAs is mediated by the porA gene expressed in P. merdae. Deletion of porA from P. merdae blunts its capacity to degrade BCAAs and leads to inefficacy in fighting against atherosclerosis. We further show that P. merdae inhibits the mTORC1 pathway in atherosclerotic plaques. In support of our preclinical findings, an in silico analysis of human gut metagenomic studies indicates that P. merdae and porA genes are depleted in the gut microbiomes of individuals with atherosclerosis. Our results provide mechanistic insights into the therapeutic potential of GMD through P. merdae in treating obesity-associated cardiovascular diseases.

The incidence of multidrug-resistant Gram-negative bacteria (MDR-GNB) pneumonia has increased in the last decade. If antibiotics are given only through intravenous, the antibiotic concentrations in lung tissue will be insufficient. Recently, nebulized antibiotics have shown effectiveness as an adjunctive therapy with intravenous antibiotics for resistant strains. Therefore, the goal of this study was to assess the efficacy and safety of adjunctive nebulized colistin sulfate in combination with intravenous antibiotics in patients with MDR-GNB pneumonia.A total of 203 patients who were infected with MDR-GNB pneumonia were selected. Based on whether patients received nebulized colistin sulfate, patients were divided into 2 groups: the NCIA group (nebulized colistin sulfate in combination with intravenous antibiotics) and the IA group (intravenous antibiotics without nebulized colistin sulfate). After propensity score matching (PSM) analysis, we compared the efficacy in terms of favorable clinical outcomes, the bacteria detection rate, days of hospital stay, days of intensive care unit (ICU) stay, days of mechanical ventilation (MV), antipyretic time, days of antibiotic therapy, and 28-day all-cause mortality. Safety was also compared between groups.A total of 116 patients met the criteria for evaluation, with 46 patients in the NCIA group and 70 patients in the IA group. After PSM, 31 patients were selected from each group. There were significant differences in favorable clinical outcomes on days 7 (67.7% vs. 32.3%, P=0.005) and 14 (71% vs. 41.9%, P=0.045) and the bacteria detection rate on days 7, 14, and the last day. There were also significant differences in days of hospital stay (17 vs. 23 days, P=0.01), antipyretic time (0.5 vs. 7.5 days, P=0.037), and days of antibiotic therapy (14 vs. 23 days, P=0.002). However, there were no significant differences in days of ICU stay, days of MV, and 28-day all-cause mortality. For nephrotoxicity, the NCIA group did not increase the risk of acute kidney injury (16.1% vs. 9.7%, P=0.707), only one patient (3.2%) in the NCIA group developed airway hyperresponsiveness (P=1.000).For MDR-GNB pneumonia, nebulized colistin sulfate as an adjuvant supportive treatment for intravenous antibiotics maybe can improve clinical efficacy and has high safety.

Retinitis pigmentosa (RP) is a group of genetic disorders resulting in inherited blindness due to the degeneration of rod and cone photoreceptors. The various mechanisms underlying rod degeneration primarily rely on genetic mutations, leading to night blindness initially. Cones gradually degenerate after rods are almost eliminated, resulting in varying degrees of visual disability and blindness. The mechanism of cone degeneration remains unclear. An understanding of the mechanisms underlying cone degeneration in RP, a highly heterogeneous disease, is essential to develop novel treatments of RP. Herein, we review recent advancements in the five hypotheses of cone degeneration, including oxidative stress, trophic factors, metabolic stress, light damage, and inflammation activation. We also discuss the connection among these theories to provide a better understanding of secondary cone degeneration in RP. Five current mechanisms of cone degenerations in RP Interactions among different pathways are involved in RP.

Cell Competition is a process by which neighboring cells compare their fitness. As a result, viable but suboptimal cells are selectively eliminated in the presence of fitter cells. In the early mammalian embryo, epiblast pluripotent cells undergo extensive Cell Competition, which prevents suboptimal cells from contributing to the newly forming organism. While competitive ability is regulated by MYC in the epiblast, the mechanisms that contribute to competitive fitness in this context are largely unknown. Here, we report that P53 and its pro-apoptotic targets PUMA and NOXA regulate apoptosis susceptibility and competitive fitness in pluripotent cells. PUMA is widely expressed specifically in pluripotent cellsin vitroandin vivo. We show that the p53-PUMA/NOXA pathway regulates mitochondrial membrane potential and oxidative status. We found that P53 regulates MYC levels in pluripotent cells, which connects these two Cell competition pathways, however, MYC and PUMA/NOXA levels are independently regulated by P53. We propose a model that integrates a bifurcated P53 pathway regulating both MYC and PUMA/NOXA levels and determines competitive fitness through regulation of mitochondrial activity.

Thermal errors are one key impact factor on the processing accuracy of numerical control machine. This study targeted at a certain vertical processing center presents a new algorithm for predictive modeling of thermal errors in numerical control machine. This algorithm is founded on back-propagation neural networks (BPNNs) and adopts beetle antennae search (BAS) to find the best weights and thresholds of BPNNs. It avoids the local minimization due to local extremums faced by traditional BPNNs. The intermingling rate and arithmetic computation efficiency of neural network algorithms are further improved. Then, a BAS-BP thermal error prediction model is built with the machine temperature changes and thermal errors as the input data. Compared with conventional BPNNs, the BPNN after particle swarm optimization suggests the convergence rate of BAS-BP is improved by 85%, the leftover mistakes between the genuine information and the anticipated information are under 1 um, and the overall prediction precision is above 90%. Thus, the new model has high precision, high anti-disturbance ability and strong robustness.

Background Metschnikowia bicuspidata is a pathogenic yesst that can cause disease in many different economic aquatic animal species. In recent years, there was a new disease outbreak in ridgetail white prawn (Exopalaemon carinicauda) in coastal areas of Jiangsu Province China that was referred to as zombie disease by local farmers. The pathogen was first isolated and identified as M. bicuspidata. Although the pathogenicity and pathogenesis of this pathogen in other animals have been reported in some previous studies, research on its molecular mechanisms is still very limited. Therefore, a genome-wide study is necessary to better understand the physiological and pathogenic mechanisms of M. bicuspidata. Result In this study, we obtained a pathogenic strain, MQ2101, of M. bicuspidata from diseased E. carinicauda and sequenced its whole genome. The size of the whole genome was 15.98 Mb, and it was assembled into 5 scaffolds. The genome contained 3934 coding genes, among which 3899 genes with biological functions were annotated in multiple underlying databases. In KOG database, 2627 genes were annotated, which were categorized into 25 classes including general function prediction only, posttranslational modification, protein turnover, chaperones, and signal transduction mechanisms. In KEGG database, 2493 genes were annotated, which were categorized into five classes, including cellular processes, environmental information processing, genetic information processing, metabolism and organismal systems. In GO database, 2893 genes were annotated, which were mainly classified in cell, cell part, cellular processes and metabolic processes. There were 1055 genes annotated in the PHI database, accounting for 26.81% of the total genome, among which 5 genes were directly related to pathogenicity (identity ≥ 50%), including hsp90, PacC, and PHO84. There were also some genes related to the activity of the yeast itself that could be targeted by antiyeast drugs. Analysis based on the DFVF database showed that strain MQ2101 contained 235 potential virulence genes. BLAST searches in the CAZy database showed that strain MQ2101 may have a more complex carbohydrate metabolism system than other yeasts of the same family. In addition, two gene clusters and 168 putative secretory proteins were predicted in strain MQ2101, and functional analysis showed that some of the secretory proteins may be directly involved in the pathogenesis of the strain. Gene family analysis with five other yeasts revealed that strain MQ2101 has 245 unique gene families, including 274 genes involved in pathogenicity that could serve as potential targets. Conclusion Genome-wide analysis elucidated the pathogenicity-associated genes of M. bicuspidate while also revealing a complex metabolic mechanism and providing putative targets of action for the development of antiyeast drugs for this pathogen. The obtained whole-genome sequencing data provide an important theoretical basis for transcriptomic, proteomic and metabolic studies of M. bicuspidata and lay a foundation for defining its specific mechanism of host infestation.

Background Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2 nd generation oral proteasome inhibitor (PI), has been approved for MT because of the convenience and tolerability. Aims We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimens in NDMM patients. Methods This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry since September 2019. After 4 cycles of front-line induction therapy, patients who reached partial response (PR) would receive autologous stem cell transplantation (ASCT) if eligible, or keep up to 5 cycles of front regimens if ineligible, then start maintenance therapy. Patients did not reach PR would switch to a 2nd-line induction for 2-5 cycles and start MT once PR was achieved. For MT, 4mg of Ixazomib was given on day 1,8,15, and 25mg of Lenalidomide every other day on days 1-21 of a 28-day cycle. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was PFS from MT. Results A total of 149 patients were enrolled, including 54 in I-MT, 65 in L-MT and 30 in IL-MT. The demographic and clinical characteristics were comparable among three groups at baseline (Table 1), including gender ratio, age, paraprotein isotype, ISS, R-ISS, response status before MT, and ASCT rate. The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were comparable. The median follow-up duration since MT was 6.1, 11.1, and 5.9 months in I-MT, L-MT and IL-MT group, respectively. Disease progression developed in 9.3%, 12.3% and 10% (N=5, 8, 3, respectively) patients. The median PFS was not reached (NR) in all groups. Only one death occurred in I-MT group. There were 84%, 72.3% and 83.3% of the patients reached very good partial response (VGPR) or better before MT, while the best response rates rose to 93%, 82.3% and 90% during maintenance. The prevalence of peripheral neuropathy was 18.5% on I-MT, 10.8% on L-MT and 30% on IL-MT. Grade 2 PN occurred in 3, 1, and 0 patients, respectively. The incidence of gastrointestinal events was 11.1%, 1.5% and 20%, respectively. Grade 3-4 hematologic toxicities was 3.7%, 4.6%, and 3.3%. Infection rates were 7.4%, 6.2% and 3.3%. Skin rashes were more common in lenalidomide containing regimens (3.7%, 7.3% and 6.7%). No drug withdrawal was related to adverse events. Conclusions Due to inadequate access to melphalan and low rate of ASCT in China, there is still a gap of PFS in NDMM patients with those in western countries. We herein design this multi-centered prospective study to evaluate if dual drug MT will further strengthen response and make up the gap. Though the primary endpoint--PFS has not been reached in all treatment groups, dual MT improves response most and is quite tolerable. Figure 1. Baseline Characteristics in three groups. Abbreviations: ISS: international staging system; R-ISS: revised-ISS; HRCAs: high risk cytogenetic abnormalities. sCR: stringent complete remission. CR: complete remission. VGPR: very good partial remission. PR: partial remission. * p ＜ 0.05. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

BACKGROUND Mutations in the beta1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2) gene can lead to impaired glycosylation of α-dystroglycan, which, in turn, causes congenital muscular dystrophy (CMD). The clinical phenotypes of CMD are broad, and there are only a few reports of CMD worldwide. CASE SUMMARY This report describes the cases of two children with CMD caused by B3GALNT2 gene mutation. The main manifestations of the two cases were abnormal walking posture, language development delay, and abnormal development of the white matter. Case 2 also had unreported symptoms of meningocele and giant arachnoid cyst. Both cases had compound heterozygous mutations of the B3GALNT2 gene, each containing a truncated mutation and a missense mutation, and three of the four loci had not been reported. Nineteen patients with CMD caused by B3GALNT2 gene mutation were found in the literature. Summary and analysis of the characteristics of CMD caused by B3GALNT2 gene mutation showed that 100% of the cases had nervous system involvement. Head magnetic resonance imaging often showed abnormal manifestations, and more than half of the children had eye and muscle involvement; some of the gene-related symptoms were self-healing. CONCLUSION B3GALNT2 gene can be used as one of the candidate genes for screening CMD, cognitive development retardation, epilepsy, and multiple brain developmental malformations in infants.

Type 2 diabetes (T2D) constitutes a worldwide health threat, and the underlying mechanism for the development and progression of T2D is complex and multifactorial. During the last decade, gut commensal bacteria have been found to play a crucial role in the regulation of T2D and related metabolic disorders. However, as a considerable component in gut microbiome, the relationship between mycobiota and T2D and related metabolic disorders remains unclear. As a proof-of-concept, we observed that the ablation of the commensal fungi in mice can protect HFD (High fat diet) induced insulin resistance and related metabolic disorders. Both ITS2 (internal transcribed spacer 2) sequencing and culture-dependent analysis show the enrichment of Candida albicans in samples from individuals with T2D (Chinese Clinical Trial Registry, ChiCTR2100042049). Repopulation with C. albicans in HFD mice accelerated insulin resistance and related disorders. Mechanically, we found the β-glucan from C. albicans mirrored the deteriorating effect of C. albicans through the dectin-1 dependent pathway. Our current findings support that gut mycobiota play an important role in the progress of T2D and indicated the preventing of gut mycobiota is a promising strategy to alleviate insulin resistance and related metabolic dysfunctions.

BackgroundOsteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed.MethodsThe study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses.ResultsAfter screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80–34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58–21.87%) and 38.05% (95% CI, 37.22–38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people.ConclusionsThis study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Rationale and Objectives: We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 minutes (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. Materials and Methods: In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n=207) and a validation cohort (n=89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child-Pugh and MELD scoring model. Results: Age (OR=1.036, 95% CI:1.002-1.070, p=0.037), Creatinine (OR=1.011, 95% CI:1.003-1.019, p=0.009), Blood ammonia (OR=1.025, 95% CI:1.006-1.044, p=0.011), ICG-R15 (OR=1.030, 95% CI:1.009-1.052, p=0.004) and Percentage decline in PPG (OR=1.068, 95% CI:1.029-1.109, p=0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child-Pugh and MELD score, this new nomogram has a better predictive value (C-index=0.828, 95% CI:0.761-0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. Conclusion: A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

BACKGROUND Tumor dormancy is an emerging field. In recent years, the field has attracted a lot of interest. OBJECTIVE This scientometric study's objectives are to review the findings in the area of tumor dormancy research and to pinpoint potential future research hotspots. METHODS Web of Science was used to retrieve English literature on tumor dormancy published in this century. After removing irrelevant material, a complete record of each publication was saved, including the title, year of publication, author's name, nationality, affiliation, journal name, keywords, and abstract. The author, country, institution, journal, year of publication, and highly cited publications were all examined using VOSviewer. RESULTS We observed that research on tumor dormancy has increased over the past 22 years, particularly from 2015 to the present, by looking at 3167 papers that were linked to the topic. As such, the United States is a world leader in this field of study. Aguirre-Ghiso, Julio A. is the author with the most publications and citations, while Harvard University is the organization with the most publications overall. The mechanisms behind tumor dormancy, methods for treating tumor dormancy, and the relationship between tumor dormancy and bone marrow have all been the subject of research. CONCLUSIONS We think that the microenvironment of tumor dormancy and immunotherapy of tumor dormancy may be the most important study fields, but research on the mechanism and treatment of tumor dormancy has continued to gain attention.

Additional file 1: Table S1. All centers participating in the study

The occurrence of singularities where spacetime curvature becomes infinite and geodesic evolution breaks down are inevitable events in classical general relativity (GR) unless one chooses an exotic matter violating weak energy condition. These singularities show up in various physical processes, such as the gravitational collapse, the birth of the universe in the standard cosmology as well as the classical solutions of the black hole spacetimes. In the last two decades, a rigorous understanding of the dynamics of quantum spacetime and the way it resolves singularities has been achieved in loop quantum cosmology (LQC) which applies the concepts and techniques of loop quantum gravity to the symmetry reduced cosmological spacetimes. Due to the fundamental discreteness of quantum geometry derived from the quantum theory, the big bang singularity has been robustly shown to be replaced by a big bounce. Strong curvature singularities intrinsic in the classical cosmology are generically resolved for a variety of cosmological spacetimes including anisotropic models and polarized Gowdy models. Using effective spacetime description the LQC universe also provides an ultra-violet complete description of the classical inflationary scenario as well as its alternatives such as the ekpyrotic and matter bounce scenarios. In this chapter we provide a summary of singularity resolution and its physical implications for various isotropic and anisotropic cosmological spacetimes in LQC and analyze robustness of results through variant models originating from different quantization prescriptions., Comment: 48 pages, 3 figures. Invited chapter to appear in the "Handbook of Quantum Gravity", edited by Cosimo Bambi, Leonardo Modesto and Ilya Shapiro, Springer (2023)

Additional file 9: Table S7. Subgroup analysis of the relation between clinical factors and overall survival (OS)

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231179542 for Cerebral multi-autoregulation model based enhanced external counterpulsation treatment planning for cerebral ischemic stroke by Bao Li, Youjun Liu, Jincheng Liu, Hao Sun, Yili Feng, Zhe Zhang and Liyuan Zhang in Journal of Cerebral Blood Flow & Metabolism

Additional file 11: Table S9. Multivariate analysis of the correlation between biomarkers and progression-free survival (PFS)

Additional file 12: Table S10. Multivariate analysis of the correlation between biomarkers and overall survival (OS)

Additional file 10: Table S8. Subgroup analysis of the correlation between clinical factors and overall response rate (ORR)

Additional file 7: Table S5. Patients who achieved complete response (n = 4)

Additional file 8: Table S6. Subgroup analysis of the relation between clinical factors and progression-free survival (PFS)

Additional file 3: Table S3. Detailed dose titration and delayed dose criteria of anlotinib

Additional file 4: Table S4. The information of primary antibodies

Additional file 2: Table S2. Detailed exclusion criteria