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Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD.We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇oThe median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇oExercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

Background: Acute type A aortic dissection complicated by limb malperfusion presents a risk of mortality to the patients. Debates exist regarding management, whether focused on reperfusion first or immediate repair. Here, we aimed to describe our experience with the management of acute type A aortic dissection (ATAAD) complicated by limb malperfusion. Methods: From January 1, 2020 to December 31, 2021, 22 consecutive patients were admitted to Xiamen Cardiovascular Hospital, due to acute type A aortic dissection complicated by limb malperfusion. All perioperative variables were recorded and analyzed. Limb malperfusion was diagnosed, according to the clinical symptoms, computed tomography angiography, and laboratory test. We adopted the clinical categories of acute limb ischemia to stratify severity of limb ischemia. Surgery strategies are as follows: Reperfusion first followed by central repair, immediate central repair, and immediate central repair followed by stenting. Results: There were 21 males and one female with an average of 53.3±11.7 years. Management strategies were as follows: immediate central repair using total arch replacement with frozen elephant trunk in 15 patients, endovascular stenting followed by central repair in four patients, and endovascular stenting after central repair in two patients. The average extracorporeal circulation time was 258.8 ± 70.5 min; the average aortic cross-clamp time was 177.9 ± 54.2 min; and the average circulatory arrest time was 45.5 ± 13.1 min. The early mortality rate was 13.6% (3/22). Two patients left the hospital voluntarily, due to cerebral infarction and bleeding. One patient underwent fasciotomy for osteofascial compartment syndrome and uneventfully was discharged. Six patients underwent continuous renal replacement therapy and hemoperfusion. Conclusion: Central repair is safe and feasible for ATAAD complicated with limb malperfusion. For serious limb malperfusion, endovascular stenting followed by central repair is a good choice with continuous renal replacement therapy (CRRT) and hemoperfusion. Hospital mortality rate is high in cases with multiple organ malperfusion.

Off-label drug use embodies a thorough clinical diagnosis and evaluation of treatment needs and should not be confused with unreasonable drug use, but it also faces potential risks with drug safety and legal issues.We first established a guideline working group. Following the guideline development process recommended by the World Health Organization Handbook and the Chinese Medical Association, the key questions were determined through literature searches of PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases. Both the evidence and the clinicians' diagnosis and treatment workload were considered to formulate the initial recommendations. Finally, two rounds of Delphi surveys and one expert seminar were organized to determine the final recommendations of this guideline. Meanwhile, we graded the recommendations based on the body of evidence.We determined nine questions and proposed a total of 23 recommendations regarding the definition of off-label use of drugs, applicable circumstances, classification of evidence, informed consent, legal basis, adverse drug reaction monitoring and evaluation, management procedure, responsibilities and obligations of different stakeholders, medical insurance reimbursement, and the national approval system.This guideline standardized clinical off-label drug use and provided suggestions and references for the management of off-label drug use.

Objective. To observe the protective effect of gynostemma glycosides on retinal ganglion cells in rats with chronically high intraocular pressure. Materials and Methods. A total of 60 rats were randomly divided into group A (the blank group, 10 rats) and chronic high IOP model group (50 rats). The IOP model group (IOP above 22 mmHg) was then randomly divided into an additional 5 groups (10 rats per group): group B (negative control group) treated with normal saline; group C treated with gynostemma glycosides 25 mg/(kg-d); group D treated with gynostemma glycosides 50 mg/(kg-d); group E treated with gynostemma glycosides 100 mg/(kg-d); and group F (positive control group) treated with VitB1 and VitB12. The eyes of each rat were monitored from day 1 to 14 (D1–D14). On day 14, rats were euthanized, after which retinal tissue and optic nerve were examined using real-time PCR, western blot, HE staining, LFB staining, and TUNEL assay. Results. Groups A, C, D, E, and F had significantly lower expression of CD11b, GFAP, Brn3α, and more TUNEL cells than in group B (all P < 0.05 ). Moreover, the relative expression of STAT3 mRNA and JAK2 (mRNA and protein) in groups A, C, D, E, and F was significantly lower than in group B ( P < 0.05 ), while in group E, the expression was lower than in group D ( P < 0.05 ). Conclusion. Gynostemma glycosides protect retinal ganglion cells in rats with chronically high intraocular pressure possibly associated with the STAT3/JAK2 signaling pathway.

The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM).We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China.A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035).This study demonstrated that species identification helps to guide therapy and predict outcomes.

There are remarkable genetic differences between animal major histocompatibility complex (MHC) systems and the human leukocyte antigen (HLA) system. HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-A-restricted responses against infection in human.A recombinant gene encoding the chimeric HLA-A30 monochain was constructed. This HHD molecule contains the following: α1-α2 domains of HLA-A30, α3 and cytoplasmic domains of H-2DWe describe a novel human β2m-HLA-A30 (α1α2)-H-2DWe established a promising preclinical research animal model of HLA-A30 Tg humanized mouse, which could accelerate the identification of novel HLA-A30-restricted epitopes and vaccine development, and support the study of HLA-A-restricted responses against infection in humans.

We present a complete representation theorem for nullnorms on bounded lattices. Explicitly, any nullnorm on a bounded lattice can be represented in terms of two order-preserving maps, a triangular conorm, a triangular norm and a conditionally associative function. As a particular case, we retrieve the known representation of nullnorms only taking values that are comparable with the annihilator (in terms of two order-preserving maps, a triangular conorm and a triangular norm). As an illustration of the representation theorem, we generate construction methods for nullnorms, especially those taking at least one value that is incomparable with the annihilator.

First, we present construction methods for interior operators on a meet semilattice. Second, under the assumption that the underlying meet semilattices constitute the range of an interior operator, we prove an ordinal sum theorem for countably many (finite or countably infinite) triangular norms on bounded meet semilattices, which unifies and generalizes two recent results: one by Dvořak and Holcapek and the other by some of the present authors. We also characterize triangular norms that are representable as the ordinal sum of countably many triangular norms on given bounded meet semilattices.

The functional roles and mechanism of the XIST in osteoarthritis and the chondrogenic differentiation of BMSCs were clarified.The expression levels of XIST, TAF15, FUT1 and YY1 were detected through quantitative RT-PCR. The protein expression of Sox9, ACAN, COL2A1 and FUT1 were detected by western blot and immunohistochemistry. The damage of cartilage tissue was detected by HE staining, and Safranin O-fast green. Alcian-Blue and Alizarin red S staining were performed to evaluate BMSCs chondrogenic differentiation. The relationship between XIST and TAF15, XIST and TAF15 were analyzed by RNA immunoprecipitation assay. Luciferase reporter assays and chromatin immunoprecipitation were performed to detect the interaction relationship between XIST and YY1. In addition, osteoarthritis mice were built to assess the function of XISTThe levels of XIST, TAF15 and FUT1 were upregulated in cartilage tissues from osteoarthritis patient. The level of XIST was decreased in BMSCs during chondrogenic differentiation. XIST overexpression inhibited the chondrogenic differentiation of BMSCs. Moreover, silencing of FUT1 reversed the effects of XIST overexpression on BMSCs chondrogenic differentiation. Mechanistically, in BMSCs, YY1 induced the expression of XIST in BMSCs, and XIST regulated FUT1 mRNA stability through targeting TAF15. Furthermore, silencing of XIST alleviated the symptoms of cartilage injury in OA mice.Taken together, these results suggested that YY1 induced XIST was closely related to the chondrogenic differentiation of BMSCs and the progression of osteoarthritis by TAF15/FUT1 axis, and may be a new OA therapeutic target.

The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved.The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH.In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia.A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients.Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

Photoreceptors are integral and crucial for the retina, as they convert light into electrical signals. Epigenetics plays a vital role in determining the precise expression of genetic information in space and time during the development and maturation of photoreceptors, cell differentiation, degeneration, death, and various pathological processes. Epigenetic regulation has three main manifestations: histone modification, DNA methylation, and RNA-based mechanisms, where methylation is involved in two regulatory mechanisms-histone methylation and DNA methylation. DNA methylation is the most studied form of epigenetic modification, while histone methylation is a relatively stable regulatory mechanism. Evidence suggests that normal methylation regulation is essential for the growth and development of photoreceptors and the maintenance of their functions, while abnormal methylation can lead to many pathological forms of photoreceptors. However, the role of methylation/demethylation in regulating retinal photoreceptors remains unclear. Therefore, this study aims to review the role of methylation/demethylation in regulating photoreceptors in various physiological and pathological situations and discuss the underlying mechanisms involved. Given the critical role of epigenetic regulation in gene expression and cellular differentiation, investigating the specific molecular mechanisms underlying these processes in photoreceptors may provide valuable insights into the pathogenesis of retinal diseases. Moreover, understanding these mechanisms could lead to the development of novel therapies that target the epigenetic machinery, thereby promoting the maintenance of retinal function throughout an individual’s lifespan.

Objective Preterm infants with bronchopulmonary dysplasia (BPD) are at increased risk for dysfunctional immune responses in the postnatal period. This study aimed to verify the hypothesis that thymic function is altered in infants with BPD and changes in the expression of thymic function-related genes affect thymic development. Study Design Included in the study were infants who had a gestational age ≤32 weeks and survived to a postmenstrual age of ≥36 weeks. The clinical features and thymic size were comparatively studied between infants with and without BPD. Thymic function and the expression of thymic function-related genes were determined in BPD infants at birth, week 2, and 4 of life. The thymic size was ultrasonographically assessed in terms of the thymic index (TI) and thymic weight index (TWI). T-cell receptor excision circles (TRECs) and gene expression were quantitatively determined by real-time quantitative reverse transcription polymerase chain reaction. Results Compared to non-BPD infants, their BPD counterparts had a shorter GA, lower birth weight, lower Apgar scores at birth, and were more likely to be of the male gender. BPD infants had an elevated incidence of respiratory distress syndrome and sepsis. TI was 1.73 ± 0.68 versus 2.87 ± 0.70 cm3 and TWI was 1.38 ± 0.45 versus 1.72 ± 0.28 cm3/kg in the BPD group versus the non-BPD group (p 0.05), but they all exhibited a significant increase at week 4 (p 0.05). Conclusion For preterm infants with BPD, reduced thymic size at birth might be associated with impaired thymic function. Thymic function was developmentally regulated in the BPD process. Key Points

Camellia crassicolumna (Theaceae) was described as an endemic species to southeastern Yunnan, China. In the most recent monograph of Camellia, seven names, including C. crispula, C. atrothea, C. makuanica, C. haaniensis, C. purpurea, C. rotundata, and C. crassicolumna var. shangbaensis, were listed as heterotypic synonyms of C. crassicolumna. Our examination of related specimens reveals that the statement ‘ovariis pilosis’ in the protologue of C. crassicolumna is incongruent with its type specimens whose ovaries are glabrous. The morphological traits of C. crassicolumna resemble C. kwangsiensis var. kwangnanica. Therefore, C. crassicolumna is reduced into C. kwangsiensis var. kwangnanica. The species status of C. crispula is reinstated with C. atrothea, C. makuanica, C. haaniensis, C. purpurea, C. rotundata, and C. crassicolumna var. shangbaensis treated as its heterotypic synonyms. A new combination, C. crispula var. multiplex, is proposed, and the lectotype of C. atrothea is designated here.

IntroductionMalonyl coenzyme A decarboxylase deficiency is caused by an abnormality in the MLYCD gene. The clinical manifestations of the disease involve multisystem and multiorgan.MethodsWe collected and analyzed a patient's clinical characteristics, genetic chain of evidence and RNA-seq. We use the search term “Malonyl-CoA Decarboxylase Deficiency” on Pubmed to collect cases reported.ResultsWe report a 3-year-old girl who is presented with developmental retardation, myocardial damage and elevated C3DC. High-throughput sequencing identified heterozygous mutation (c.798G>A, p.Q266?) in the patient inherited from her father. The other heterozygous mutation (c.641+5G>C) was found in the patient inherited from her mother. RNA-seq showed that there were 254 differential genes in this child, among which 153 genes were up-regulated and 101 genes were down-regulated. Exon jumping events occurred in exons encoding PRMT2 on the positive chain of chromosome 21, which led to abnormal splicing of PRMT2. (PDiscussionIt is the first report about the locus, adding a new item to the MLYCD mutation library. Developmental retardation and cardiomyopathy are the most common clinical manifestations, with commonly elevated malonate and malonyl carnitine levels in children.

Background Lifestyle changes are important for the prevention and management of metabolic syndrome (MetS), but studies that focus on gender differences in the lifestyle risk factors of MetS are limited in China. This research aimed to generate a healthy lifestyle index (HLI) to assess the behavioral risk factors of MetS and its components, and to explore the gender differences in HLI score and other influencing factors of MetS. Methods A convenience sample of 532 outpatients were recruited from a general hospital in Changsha, China. The general information and HLI scores [including physical activity (PA), diet, smoking, alcohol use, and body mass index (BMI)] of the subjects were collected through questionnaires, and each patient’s height, weight, waist circumference, and other physical signs were measured. Logistic regression analysis was used to analyze the risk factors of MetS and its components. Results The prevalence of MetS was 33.3% for the whole sample (46.3% in males and 23.3% in females). The risk of MetS increased with age, smoking, unhealthy diet, and BMI in males and with age and BMI in females. Our logistic regression analysis showed that lower HLI (male: OR = 0.838,95%CI = 0.757–0.929; female: OR = 0.752, 95%CI = 0.645–0.876) and older age (male: OR = 2.899, 95%CI = 1.446–5.812; female: OR = 4.430, 95%CI = 1.640–11.969) were independent risk factors of MetS, for both sexes. Conclusion Low levels of HLI and older ages were independent risk factors of MetS in both males and females. The association between aging and MetS risk was stronger in females, while the association between unhealthy lifestyles and MetS risk was stronger in males. Our findings reinforced the expected gender differences in MetS prevalence and its risk factors, which has implications for the future development of gender-specific MetS prevention and intervention programs.

Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, play a critical role in metabolic regulation and intracellular communication. Stem cell-derived EVs are considered to have the potential for regeneration, like stem cells, while simultaneously avoiding the risk of immune rejection or tumour formation. The therapeutic effect of stem cell-derived EVs has been proven in many diseases. However, the molecular mechanism of stem cell-derived EVs in retinal repair and regeneration has not been fully clarified. In this review, we described the biological characteristics of stem cell-derived EVs, summarized the current research on stem cell-derived EV treatment in retinal repair and regeneration, and discussed the potential and challenges of stem cell-derived EVs in translational medicine.

BackgroundThe significance of implicit self-schema and other-schema in major depressive disorder (MDD) is highlighted by both cognitive theory and attachment theory. The purpose of the current study was to investigate the behavioral and event-related potential (ERP) characteristics of implicit schemas in MDD patients.MethodsThe current study recruited 40 patients with MDD and 33 healthy controls (HCs). The participants were screened for mental disorders using the Mini-International Neuropsychiatric Interview. Hamilton Depression Rating Scale-17 and Hamilton Anxiety Rating Scale-14 were employed to assess the clinical symptoms. Extrinsic Affective Simon Task (EAST) was conducted to measure the characteristics of implicit schemas. Meanwhile, reaction time and electroencephalogram data were recorded.ResultsBehavioral indexes showed that HCs responded faster to positive self and positive others than negative self (t = −3.304, p = 0.002, Cohen’s d = 0.575) and negative others (t = −3.155, p = 0.003, Cohen’s d = 0.549), respectively. However, MDD did not show this pattern (p > 0.05). The difference in other-EAST effect between HCs and MDD was significant (t = 2.937, p = 0.004, Cohen’s d = 0.691). The ERP indicators of self-schema showed that under the condition of positive self, the mean amplitude of LPP in MDD was significantly smaller than that in HCs (t = −2.180, p = 0.034, Cohen’s d = 0.902). The ERP indexes of other-schema showed that HCs had a larger absolute value of N200 peak amplitude for negative others (t = 2.950, p = 0.005, Cohen’s d = 0.584) and a larger P300 peak amplitude for positive others (t = 2.185, p = 0.033, Cohen’s d = 0.433). The above patterns were not shown in MDD (p > 0.05). The comparison between groups found that under the condition of negative others, the absolute value of N200 peak amplitude in HCs was larger than that in MDD (t = 2.833, p = 0.006, Cohen’s d = 1.404); under the condition of positive others, the P300 peak amplitude (t = −2.906, p = 0.005, Cohen’s d = 1.602) and LPP amplitude (t = −2.367, p = 0.022, Cohen’s d = 1.100) in MDD were smaller than that in HCs.ConclusionPatients with MDD lack positive self-schema and positive other-schema. Implicit other-schema might be related to abnormalities in both the early automatic processing stage and the late elaborate processing stage, while the implicit self-schema might be related only to the abnormality in the late elaborate processing stage.

Objective: To explore the application of magnetic resonance imaging (MRI) in the evaluation of radiation-induced sinusitis (RIS), MRI-based scoring system was used to evaluate the development regularity, characteristics and influencing factors of RIS in nasopharyngeal carcinoma (NPC) patients. Patients and methods:A retrospective analysis was performed by collecting the clinical and MRI data of 346 NPC patients to analyze the characteristics and prognosis of RIS. The predictive model was constructed according to the influencing factors of RIS. Results: (1) In the 2-year follow-up after radiotherapy (RT), there was significant change in L-M score in both groups of NPC patients (sinusitis before RT group: F=6.542, p=0.009 vs. non-sinusitis before RT group: F=11.702, p=0.000). After 6 months of RT, the L-M scores of the two groups tended to plateau (sinusitis before RT group: F=0.458, p=0.766 vs. non-sinusitis before RT group: F=0.500, p=0.736). (2) The prevalence of sinusitis in two groups of NPC patients (without or with sinusitis before RT) was 83% vs. 93%, 91% vs. 99%, 94% vs. 98% at 1, 6 and 24 months after RT, respectively. (3) In the patients without sinusitis before RT, the incidence of sinusitis in maxillary and anterior/posterior ethmoid, sphenoid and frontal sinuses was 87.1%, 90.0%/87.1%, 49.5%, 11.8% respectively, 1 month after RT. (4) A regression model was established according to the univariate and multivariate analysis of the factors related to RIS (smoking history: p=0.000, time after RT: p=0.008 and TNM staging: p=0.040). Conclusion: (1) RIS is a common complication in NPC patients after RT. This disorder progressed within 6 months after RT, stabilized and persisted within 6 months to 2 years. There is a high incidence of maxillary sinus and ethmoid sinus inflammation in NPC patients after RT. (2) Smoking history, time after RT and TNM staging were significant independent risk factors for RIS. (3) The intervention of the risk factors in the model may prevent or reduce the occurrence of RIS in NPC patients.

The local tea plant population resources are rich in genetic variation, which is the natural treasure house of tea genes and the main source of breeding excellent tea cultivars. However, the genetic information of most local tea plant populations is still unknown. In this study, the genetic diversity and population structure of four main local tea plant populations in Jiangxi Province of China were explored by combining phenotypic characters identification and simple sequence repeats (SSR), and the loci associated with phenotypic characters were screened. The results of genetic diversity analysis of phenotype and SSR were consistent. It was found that the genetic diversity of population species was higher than that of wild species. The order of genetic diversity index of the four tea plant populations was Wuyuan > Fuliang > Suichuan > Ningdu. The single-plants of each population were heterozygotes, and Wuyuan had the highest heterozygosity. The clustering results of phenotypes and SSR on tea plant populations were not completely consistent. SSR could more effectively distinguish tea plant populations. Four tea populations could be clustered into three groups. Further analysis found that the geographical location of tea population distribution would affect its gene exchange. In addition, 9 SSR loci were screened and were significantly associated with 9 phenotypic characters (P

Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)-associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti–CD20-IFNα) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti–CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti–CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti–PD-L1 treatment. Cancer Immunol Res; 5(7); 560–70. ©2017 AACR.

Supplementary Figure 1. The depletion efficiency of normal B cell population by anti-CD20; Supplementary Figure 2. Anti-CD20-IFNα fusion protein demonstrated normal biological activities; Supplementary Figure 3. Intratumoral administration of type I IFN can effectively control B cell lymphoma; Supplementary Figure 4. BL3750 cells are sensitive and A20 cells are resistant to IFNα treatment; Supplementary Figure 5. CD8+ T cells are essential for i.v administrated anti-CD20-IFNα mediated tumor control; Supplementary Figure 6. CD4+ T cells are not essential for anti-CD20-IFNα mediated tumor control; Supplementary Figure 7. FTY720 induces a remarkable decrease of peripheral T cells; PGS-1. Anti-CD20 Gene Sequence; PGS-2. IFNα-hIgG1 Gene Sequence; PGS-3. Anti-CD20-IFNα Gene Sequence.

Supplementary Figure 5. FTY720 could efficiently prohibit lymphocytes from exiting the lymphoid organ.

Supplementary Figure 4. The therapeutic function of anti-CD20 is NK cell-independent.

Supplementary Figure 1. The therapeutic effect of anti-CD20 is not CD4+ T cell-dependent.

Supplementary Figure S1 shows the procedure to generate radioresistant HCT1166GyR cells; Supplementary Figure S2 shows reporter constructs of NHEJ and HR pathway; Supplementary Figure S3 shows representative images of IHC assays; Supplementary Figure S4 show the detailed data of screening candidate radioresistant genes; Supplementary Figure S5 shows RFC4 expression in CRC cells and tissues after radiation; Supplementary Figure S6 shows the representative clonogenic pictures for Figure 1C; Supplementary Figure S7 shows representative charts of Annexin V/PI double staining assays for Figure 1F; Supplementary Figure S8 shows the effects of RFC4 on γ-H2AX and pATM levels after radiation; Supplementary Figure S9 shows the additional evidences of RFC4 to promote NHEJ- but not HR-mediate DNA repair; Supplementary Figure S10 shows the effects of RFC4 on the chemotherapeutic drug resistance in HCT116 cells.

Supplementary Figure 7. Model for generation of anti-tumor T-cell response induced by anti-CD20 treatment.

Supplementary Figure 6. The percentage of CTLA4+ CD8+ T cells is much lower than that of CTLA-4+ Treg cells in the large established B-cell lymphoma.

Supplementary Table S4 shows the correlation of clinicopathological parameters and RFC4 expression.

Supplementary Tables S5 & S6 show the candidate genes picked out in HCT116 and HT29 cells; Supplementary Tables S7 & S8 show the proteins might bind with RFC4, detected by IP-MS in HCT116 and HT29 cells.

Supplementary Figure 3. Clophosome could deplete macrophage efficiently, without depleting DCs.

Supplementary Table S1 shows the sequences of siRNAs; Supplementary Table S2 shows the informations of shRNAs; Supplementary Table S3 shows the sequences of quantitative PCR Primers.

Supplementary Figure 2. DT could deplete DCs efficiently in CD11c-DTR mice, without affecting macrophages so much.