[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.

Objective:To investigate the application of the preauricular fascial pedicled mandibular flap for wound healing after upper-middle face skin tumor resection.Methods:The patients with upper-middle face skin tumor were selected, who were treated in the Department of Oncology, First Affiliated Hospital of Bengbu Medical College from December 2018 to October 2020. According to the location and size of the defects, large defects of facial skin and soft tissues were primarily repaired by using the preauricular fascial pedicled mandibular flap.Results:This study included 10 cases of skin tumour, 5 males and 5 females, aged from 55 to 86 years. The mandibular flaps were all developed well and the appearance and function were satisfactory. After 3-22 months of follow-up, no local recurrence and complications occurred, such as difficulty of eyelid closure and deviation of commissure.Conclusions:Preauricular fascial pedicled mandibular flap technique has such advantages as simple operation, safety and reliability. The flap can be obtained with a long pedicle and a large area and it also can achieve a maximum of 180° rotation to repair postoperative tissue defects in upper-middle face of skin cancer resection, leading to good outcome of appearance and functionality.

Objective:To investigate the application of preauricular fascial pedicle mandibular flap for wound healing in upper-middle face of skin tumour.Methods:Select upper-middle face of skin tumour patients who were treated in department of oncology, first affiliated hospital of Bengbu medical college from December 2018 to October 2020..According to the defect site and scope, primary repair of a large range of skin and soft tissues of face by using preauricular fascial pedicle mandibular flap.Results:The group inclouded 10 cases of skin tumour, 5 males and 5 females, aged from 55 to 86 years, mandibular flap were all developed well and the configuration and function were satisfactory. After 3- 22 months of follow-up, no local recurrence and complications, such as difficulty of eyelid closure and deviation of mouth angle.Conclusions:Preauricular fascial pedicle mandibular flap technique with simple operation, safety and reliability.The flap with long pedicle and large area can be cut and it also can achieve 180° rotation to repair postoperative tissue defect wound in upper-middle face of skin cancer, lead to good effects of appearance and functionality.

Objective:To investigate the application of the preauricular fascial pedicled mandibular flap for wound healing after upper-middle face skin tumor resection.Methods:The patients with upper-middle face skin tumor were selected, who were treated in the Department of Oncology, First Affiliated Hospital of Bengbu Medical College from December 2018 to October 2020. According to the location and size of the defects, large defects of facial skin and soft tissues were primarily repaired by using the preauricular fascial pedicled mandibular flap.Results:This study included 10 cases of skin tumour, 5 males and 5 females, aged from 55 to 86 years. The mandibular flaps were all developed well and the appearance and function were satisfactory. After 3-22 months of follow-up, no local recurrence and complications occurred, such as difficulty of eyelid closure and deviation of commissure.Conclusions:Preauricular fascial pedicled mandibular flap technique has such advantages as simple operation, safety and reliability. The flap can be obtained with a long pedicle and a large area and it also can achieve a maximum of 180° rotation to repair postoperative tissue defects in upper-middle face of skin cancer resection, leading to good outcome of appearance and functionality.

Objective:To investigate the application of preauricular fascial pedicle mandibular flap for wound healing in upper-middle face of skin tumour.Methods:Select upper-middle face of skin tumour patients who were treated in department of oncology, first affiliated hospital of Bengbu medical college from December 2018 to October 2020..According to the defect site and scope, primary repair of a large range of skin and soft tissues of face by using preauricular fascial pedicle mandibular flap.Results:The group inclouded 10 cases of skin tumour, 5 males and 5 females, aged from 55 to 86 years, mandibular flap were all developed well and the configuration and function were satisfactory. After 3- 22 months of follow-up, no local recurrence and complications, such as difficulty of eyelid closure and deviation of mouth angle.Conclusions:Preauricular fascial pedicle mandibular flap technique with simple operation, safety and reliability.The flap with long pedicle and large area can be cut and it also can achieve 180° rotation to repair postoperative tissue defect wound in upper-middle face of skin cancer, lead to good effects of appearance and functionality.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

Objective:To assess the treatment and prognosis of vulvar melanoma.Methods:A total of 59 cases of primary vulvar melanoma admitted to Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1st, 1981 to November 30th, 2019 were collected. The clinical characteristics, treatment, survival and prognostic factors of vulvar melanoma were analyzed retrospectively. The end date of follow-up was January 15th, 2020.The median follow-up time was 26.0 months (range:2-198 months).Results:(1) Clinical characteristics: the median age of 59 patients with vulvar melanoma was 56 years old (range:18-83 years old). According to the American Joint Committee on Cancer stage manual, there were 18, 7, 26 and 8 cases of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively. The lesion of 38 cases was single and the other 21 cases were multiple. The largest diameter of the tumor ranged from 0.3 to 17.0 cm.The surface of the lesion was ulcerated in 17 cases. (2) Treatment: a total of 59 cases with vulvar melanoma, 56 patients received surgery, 36 cases of them received radical resection of vulva and 20 received local extended resection of vulvar tumor due to unilateral vulva lesion. Three patients did not receive surgery,one received chemotherapy combined with interferon, one received interferon, and one received radiotherapy. Lymph node management: among the 56 patients treated by surgery, 37 patients received inguinal lymphadenectomy, 24 (65%, 24/37) of whom were confirmed with inguinal lymph node metastasis by postoperative pathological examination. Inguinal lymph nodes enlargement were not found in 19 cases by preoperative imaging and clinical examination. In these 19 patients, three patients received inguinal lymph node biopsy, among them, one (1/3) patient was confirmed with inguinal lymph node metastasis by postoperative pathological examination, and the remaining 16 patients did not receive inguinal lymph node surgery. Postoperative adjuvant treatment: among the 56 patients who received surgery, 31 received adjuvant chemotherapy，one received adjuvant radiotherapy, four received interferon therapy, 17 received combination therapy including chemotherapy, and three did not receive postoperative adjuvant therapy. (3) Survival:during the follow-up period, the median survival time of 59 patients with vulvar melanoma was 30.0 months (range:2.0-198.0 months). The 3-year survival rate was 42.5%, and the 5-year survival rate was 23.8%. The median survival time of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 72.0, 45.0, 24.0 and 23.0 months, respectively. The difference among stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ were statistically significant （ P<0.01）. The median survival time of patients undergoing radical resection of the vulva (35.0 months) and local enlarged tumor resection (29.0 months) were significantly longer than that of patients without surgery (9.0 months, P<0.01). The median survival time of the patients who underwent inguinal lymphadenectomy, lymph node biopsy and those who did not undergo surgery were 35.0, 32.0 and 30.0 months, respectively. There were no significant differences among the 3 groups ( P>0.05). The median survival time of postoperative adjuvant chemotherapy patients (49.0 months) were significantly longer than that of postoperative adjuvant radiotherapy, interferon,and combination therapy including chemotherapy (9.0, 14.0 and 26.0 months, respectively, all P<0.01). (4) Prognostic factors: the univariate analysis showed that stage, vulvar operation and postoperative adjuvant treatment were the risk factors affecting the prognosis of patients with vulvar melanoma ( P<0.01). Multivariate analysis revealed that stage alone was an independent risk factor affecting the prognosis of patients with vulvar melanoma ( P<0.01). Conclusions:The prognosis of patients with vulvar melanoma is poor, and stage is an independent prognostic factor.Surgery combined with postoperative adjuvant chemotherapy may achieve relatively good results.

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)?Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.