Cell membrane-modified nanoparticles (NPs) have attracted widespread attention as a new approach for malignant brain tumors in recent years. This method can enhance the targeting, biocompatibility, and circulation time of NPs by preserving the characteristics of source cell membrane, thereby ensuring efficient drug delivery to intracranial lesions. This paper focuses on the research progress in this field, especially advantages of NPs penetrating the blood-brain barrier, immune evasion and drug delivery, as well as modified effect of different cell membrane on NPs, in order to provide help for treatment of malignant brain tumors.

Ferroptosis is a novel form of cell death discovered in recent years, characterized by iron-dependent cell death featuring the peroxidation of polyunsaturated fatty acid phospholipids. Recent studies have found that radiotherapy can induce ferroptosis in tumor cells through ionizing radiation, and the combination of radiotherapy with small molecule or nano-scale ferroptosis inducers can inhibit tumor growth and enhance radiosensitization. This review summarizes the mechanisms of ferroptosis and the pathways through which radiotherapy induces ferroptosis, and also explores the potential application prospects of small molecule drugs and nanomaterials in mediating ferroptosis for the radiosensitization of tumor treatment.

Lipophosphatidic acid(LTA)was used to stimulate Mac-T cells,and the expression lev-els and phosphorylation levels of key proteins of nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathway and the expression levels of upstream key action factors TLR4 and MyD88 proteins were detected by Western blot,and EDU assay was used to detect cell proliferation levels and flow cytometry was used to detect apoptosis.The results showed that acti-vation of GPR120 significantly decreased the phosphorylation levels of LTA-induced NF-κB(P65 and IκBα)(P＜0.01)and MAPK(JNK,ERK,p38)(P＜0.01)in Mac-T cells;inhibition of GPR120 was able to upregulate LTA-induced NF-κB(p65 and IκBα)in Mac-T cells(P＜0.01)and MAPK(JNK,ERK,p38)phosphorylation levels(P＜0.01);and activation of GPR120 significantly allevia-ted LTA-induced upregulation of TLR4 and MyD88(P＜0.01);inhibition of GPR120 significantly exacerbated LTA-induced upregulation of TLR4 and MyD88(P＜0.05);LTA stimulation led to a trend of diminished Mac-T cell proliferation and significantly increased apoptosis,whereas activa-tion of the GPR120 gene significantly increased cell activity(P＜0.01),promoted cell proliferation and significantly reduced apoptosis(P＜0.05)thereby alleviating the damage to Mac-T cells by LTA;LTA stimulation led to a highly significant increase in apoptosis(P＜0.01).In contrast,acti-vation of the GPR120 gene significantly reversed the increase in the apoptosis rate of Mac-T cells induced by LTA(P＜0.01),while inhibition of the GPR120 gene enhanced the apoptosis-promo-ting effect of LTA(P＜0.05),indicating that activation of the GPR120 gene attenuated the in-crease of apoptosis rate caused by LTA-induced inflammatory Mac-T cells.The results suggest that GPR120 can regulate inflammation by mediating TLR4 and MyD88 expression to inhibit NF-κB/MAPK inflammatory pathway activation and can promote cell proliferation.

Objective:To investigate the influence of the depth of invasion on the prognosis of pT1 stage mid-thoracic esophageal cancer patients undergoing left thoracotomy.Methods:Retrospectively analyze the clinicopathological data of 139 patients with pT1N0M0 stage of mid-thoracic esophageal cancer who meet the enrollment criteria. Firstly, the prognosis and influencing factors of the whole group were analyzed. The differences in prognosis, local recurrence and distant metastasis between PT1A and PT1B patients were compared, and the influence of different infiltration depth on prognosis and treatment failure of patients was analyzed. SPSS 19.0 statistical software was used for statistical analysis.Results:The 1-year, 3-year and 5-year overall survival(OS) and disease-free survival(DFS) were 95.0%, 87.8%, 82.0% and 91.4%, 84.2%, 77.0%, respectively. There were significant differences in OS( χ2=7.500, P=0.006) and DFS( χ2=7.354, P=0.007) at 1, 3 and 5 years between pT1a and pT1b patients. Cox multivariate analysis showed that pT stage and pathological type were independent prognostic factors for OS and DFS( P<0.05). There were no significant differences in OS( χ2=0.734, P=0.693) and DFS( χ2=0.7690, P=0.681) of pT1a tumors with different invasion depths. There were significant differences in OS( χ2=15.368, P<0.001) and DFS( χ2=27.470, P<0.001) at 1, 3 and 5 years of pT1b tumors with different invasion depths. The recurrence rate of pT1b(23.8%) was significantly higher than that of pT1a(5.3%)( χ2=5.274, P=0.022). The distant metastasis rate of the former(10.9%) was also significantly higher than that of the latter(0)( χ2=4.494, P=0.034). There were significant differences in local recurrence rate( χ2=17.051, P<0.001) and distant metastasis rate( χ2=15.460, P<0.001) among pT1b patients with different infiltration depths. Logistic multivariate analysis showed that the depth of infiltration was an independent factor affecting the occurrence of local recurrence in stage pT1b patients after treatment( P<0.001). Pathological type( P=0.003) and infiltration depth( P=0.027) were independent factors affecting the occurrence of distant metastasis. Conclusion:pT1a period and pT1b period after the prognosis and treatment of patients with different failure modes, and pT1b period in patients with different infiltration depth and the prognosis of patients and its failure mode after treatment significantly related, infiltration depth of pT1b period after treatment in patients with the independence of the influencing factors of failure, suggest that clinical doctors should pay attention to pT1b period in patients with postoperative adjuvant therapy. This conclusion needs to be confirmed by large prospective studies of cases.

Objective:To explore the detection and segmentation of ischemic core infarct volume of the acute stroke in diffusion weighted imaging (DWI) images using cascaded VB-Net.Methods:MRI data of 1 500 patients (2 456 lesions) with acute ischemic stroke in Henan Provincial People′s Hospital from December 2016 to December 2018 were retrospectively analyzed. Firstly, manual segmentation of ischemic core was performed on DWI images (b=1 000 s/mm 2), and then all data were divided into training set, validation set and independent test set by 8∶1∶1. Then, the cascaded VB-Net was constructed, and the core infarct was automatically detected and segmented in the test set. Interclass correlation coefficient (ICC) was used to evaluate the consistency of volume size measured by manual segmentation and cascaded VB-Net. The patients were divided into large ischemic core lesion group (ischemic core volume ≥10 ml) and small ischemic core lesion group (ischemic core volume<10 ml), and the Dice coefficient difference between the two groups was compared using Mann-Whitney U test. Results:In independent test set, cascaded model had the detection rate of 94.6% (243/257) with Dice coefficient of 0.76 (0.68, 0.84). The agreement of cacade VB-Net segmented [4.19(1.21,14.13)ml] and manual segmented ischemic core infarct volume [4.08(1.19,17.92)ml] was high (ICC=0.97, P<0.001). There was no significant difference in Dice coefficient between large and small lesion groups [0.76 (0.69, 0.85), 0.76 (0.67, 0.84), Z=-0.44, P=0.657]. Conclusions:The cascaded VB-Net model provided a tool to realize automatic detection, segmentation, and calculation of ischemic core infarct volume. It has good segmentation accuracy and high consistency with manual segmentation, which can provide an auxiliary decision-making tool for the selection of treatment plans.

Objective: To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors. Methods: Data of 101 patients who were diagnosed with stage II-III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II-III rectal cancer by high-resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+ and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm; (4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0-1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow-up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch-and-wait strategy was selected according to the therapeutic effect and patients' wishes. Short-term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed. Results: The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0±1.3. Seventy-five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0±0.9 and 2.8±1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch-and-wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3. Conclusion TNT is safe and has good short-term efficacy for locally advanced rectal cancer patients with high risk factors.

Objective To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors. Methods Data of 101 patients who were diagnosed with stage II?III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II?III rectal cancer by high?resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm;(4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0?1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow?up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch?and?wait strategy was selected according to the therapeutic effect and patients' wishes. Short?term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed. Results The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0 ± 1.3. Seventy?five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0 ± 0.9 and 2.8 ± 1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch?and?wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3. Conclusion TNT is safe and has good short?term efficacy for locally advanced rectal cancer patients with high risk factors.

Objective To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors. Methods Data of 101 patients who were diagnosed with stage II?III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II?III rectal cancer by high?resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm;(4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0?1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow?up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch?and?wait strategy was selected according to the therapeutic effect and patients' wishes. Short?term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed. Results The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0 ± 1.3. Seventy?five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0 ± 0.9 and 2.8 ± 1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch?and?wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3. Conclusion TNT is safe and has good short?term efficacy for locally advanced rectal cancer patients with high risk factors.

Avian leukosis virus subgroup J (ALV-J) is an avian retrovirus that can induce myelocytomas. A high-frequency mutation in gene envelope endows ALV-J with the potential for cross-species transmission. We wished to ascertain if the ALV-J can spread across species under selection pressure in susceptible and resistant hosts. First, we inoculated (in turn) two susceptible host birds (specific pathogen-free (SPF) chickens and turkeys). Then, we inoculated three resistant hosts (pheasants, quails and ducks) to detect the viral shedding, pathologic changes, and genetic evolution of different isolates. We found that pheasants and quails were infected under the selective pressure that accumulates stepwise in different hosts, and that ducks were not infected. Infection rates for SPF chickens and turkeys were 100% (16/16), whereas those for pheasants and quails were 37.5% (6/16) and 11.1% (3/27). Infected hosts showed immune tolerance, and inflammation and tissue damage could be seen in the liver, spleen, kidneys and cardiovascular system. Non-synonymous mutation and synonymous ratio (NS/S) analyses revealed the NS/S in hypervariable region (hr) 2 of pheasants and quails was 2.5. That finding suggested that mutation of isolates in pheasants and quails was induced by selective pressure from the resistant host, and that the hr2 region is a critical domain in cross-species transmission of ALV-J. Sequencing showed that ALV-J isolates from turkeys, pheasants and quails had moved away from the original virus, and were closer to the ALV-J prototype strain HPRS-103. However, the HPRS-103 strain cannot infect pheasants and quails, so further studies are needed.
Amino Acid Sequence ; Animals ; Avian Leukosis ; transmission ; virology ; Avian Leukosis Virus ; classification ; genetics ; physiology ; Chickens ; Ducks ; virology ; Galliformes ; virology ; Host Specificity ; Molecular Sequence Data ; Poultry Diseases ; transmission ; virology ; Quail ; virology ; Sequence Alignment ; Turkeys ; virology ; Viral Envelope Proteins ; chemistry ; genetics ; metabolism

OBJECTIVETo study the efficacy and safety of rituximab (RTX) in the treatment of idiopathic thrombotic thrombocytopenic purpura (ITTP).

METHODSAmong 17 ITTP patients, nine cases of the RTX group were administrated with RTX plus plasma exchange (PEX) and steroids. Eight cases of the control group received PEX plus steroids±other immune inhibitors. Patients received RTX 375 mg/m², 1 per week for 4 weeks. The laboratory parameters, including hemogram, LDH, ADAMTS13 activities and its inhibitors, and the ratio of B lymphocytes in peripheral blood were monitored. The number of PEX, total plasma volumes, remission time, relapse ratio and adverse effects in both groups were compared.

RESULTSThe median number of PEX/median total plasma volumes in the RTX and control group were 5(2-8)/9.6(4.0-15.4) L and 6(4-9)/11.2(7.5-14.6) L, respectively. Patients in the RTX and control group achieved hematologic remission at the median time of 15(5-20) days and 22(7-36) days, respectively. And the median time of immunological remission in the two groups was 2(2-8) and 2(2-4) weeks, respectively. ADAMTS13 activities increased significantly after 2 weeks in both two groups. There was no relapse in the RTX group, while 4 patients relapsed in the control group. The percentage of B lymphocytes in peripheral blood obviously deduced one week after first dose of RTX infusion compared with the level before treatment [(2.19±5.11)% vs (18.39±7.15)%, P<0.001], and began to gradually increase 9 months later. Severe adverse events were not observed in RTX group during the therapeutic procedure and follow-up, but one patient, who had sustained immunologic remission, died of severe pneumonia 7 months later.

CONCLUSIONIn the treatment of ITTP, RTX in conjunction with PEX and steroids appeared to be a safe and effective therapy, with fast and sustained remission in hematology and even in immunology, with lower relapse rate and less adverse effects. But patients needed to be paid attention to prevent and treat infectious events in time.