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Cancer immunotherapy is a strategy that is moving to the frontier of cancer treatment in the current decade. In this study, we show evidence that 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs), act as immunogenic cell death (ICD) inducers, stimulating an antitumor response which results in synergistic antitumor activity by combining anti-PD-L1 antibody (aPD-L1) in vivo. To investigate the antitumor immunity induced by NPPA-PTX NPs, the expression of both ICD marker calreticulin (CRT) and high mobility group box 1 (HMGB1) were analyzed. In addition, the antitumor activity of NPPA-PTX NPs combined with aPD-L1 in vivo was also investigated. The immune response was also measured through quantitation of the infiltration of T cells and the secretion of pro-inflammatory cytokines. The results demonstrate that NPPA-PTX NPs induce ICD of MDA-MB-231 and 4T1 cells through upregulation of CRT and HMGB1, reactivating the antitumor immunity via recruitment of infiltrating CD3+, CD4+, CD8+ T cells, secreting IFN-γ, TNF-α, and the enhanced antitumor activity by combining with aPD-L1. These data suggest that the combined therapy has a synergistic antitumor activity and has the potential to be developed into a novel therapeutic regimen for cancer patients.

Objective:. This study was performed to explore the conversion of adipose-derived stem cells (ADSCs) into sweat gland-like cells for the purpose of sweat gland regeneration. Methods:. ADSCs and human sweat gland (hSG) cells were isolated, cultured, and identified. The ADSCs were then cultured in combination with epidermal growth factor and/or cocultured with hSG cells in a Transwell coculturing system to transform the ADSCs into hSG-like cells. Phenotypic changes of the ADSCs were examined by morphological observation and immunocytochemical analysis of specific markers. Results:. The ADSCs showed sweat gland-like morphologic changes and expressed sweat gland markers (cytokeratins 7, 14, and 18). Conclusion:. These findings revealed that ADSCs can differentiate into hSG-like cells after coculture in a Transwell system and that epidermal growth factor can enhance the efficiency of differentiation. ADSCs may serve as a potential source of cells for sweat gland regeneration.

The antitumor immune response involves a cascade of cancer-immunity cycles. Developing a combination therapy aimed at the cancer-immunity cycle is of great importance. In this research, we designed and tested a combined therapeutic-Au nanorod (AuNR)/doxorubicin (DOX) gel (AuNR/DOX gel)-in which the sustained release of DOX was controlled by Pluronic gel. DOX served as an immunogenic tumor cell death (ICD) inducer, triggering the production of damage-associated molecular patterns (DAMPs). Mild photothermal therapy (Mild PTT) produced by 880 nm laser-irradiated AuNRs also generated tumor-associated antigens. Maleimide-modified liposomes (L-Mals), as antigen capturing agents, promoted tumor antigen uptake by DCs. Ultimately, more CD8+ T cells and fewer regulatory T cells (Tregs) infiltrated the tumor, eliciting antitumor responses from the PD-L1 antibody. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system. STATEMENT OF SIGNIFICANCE: Developing a combination therapy for cancer-immunity cycle is of great importance due to antitumor immune response involving a cascade of cancer-immunity cycles. Cancer-immunity cycle usually includes tumor antigen release, antigen presentation, immune activation, trafficking, infiltration, specific recognition of tumor cells by T cells, and finally cancer cell killing. In this research, we designed a combination strategy based on Au nanorod/doxorubicin gel via mild photothermal therapy combined with antigen-capturing liposomes and anti-PD-L1 agent promoting a positive shift in the cancer-immunity cycle. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system.

Zhuo-Yue Li,1,2 Yi-Fan Yin,1,2 Yang Guo,1,2 Hui Li,1,2 Mei-Qi Xu,1,2 Man Liu,1,2 Jing-Ru Wang,1,2 Zhen-Han Feng,1,2 Xiao-Chuan Duan,1,2 Shuang Zhang,1,2 Shuai-Qiang Zhang,1,2 Guang-Xue Wang,2 Ai Liao,2 Shu-Min Wang,3 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 3Department of Ultrasound, Peking University Third Hospital, Peking University, Beijing 100191, People’s Republic of ChinaCorrespondence: Xuan ZhangDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaTel/Fax +86-10-82805765Email xuanzhang@bjmu.edu.cnShu-Min WangDepartment of Ultrasound, Peking University Third Hospital, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaEmail shuminwang2014@163.comIntroduction: Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti–inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN.Methods: Metastatic breast tumor 4T1/luc cells and hepatocellular carcinoma HepG2 cells were selected as cell models. The effects of FFA in vitro on cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in 4T1/luc and HepG2 cells were investigated. The in vivo anti-tumor activity of MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) was evaluated in a 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model, respectively.Results: The results indicated that FFA could markedly decrease cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in both 4T1/luc and HepG2 cells. The enhanced anti-tumor activity of MSNM@SFN+FFA compared with that of MSNM@SFN was confirmed in the 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model in vivo, respectively.Discussion: MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) developed in this study is an alternative strategy for improving the therapeutic efficacy of MSNM@SFN via co-administration with NSAIDs.Keywords: sorafenib mesoporous silica nanomatrix, MSNM@SFN, flufenamic acid, FFA, PGE2, AKR1C1, AKR1C3, 4T1/luc, HepG2

Labia minora hypertrophy, in combination with clitoral hood protrusion, is a common deformity encountered in clinic practice and should be treated as a compound entity. Most targeted surgical procedures are too complex to understand and master. Herein, we introduce a relatively simple method to correct this deformity. In this study, we retrospectively review our experience treating patients with deformity of labia minora hypertrophy combined with clitoral hood protrusion between January 2017 and November 2019. All patients received correction surgery to repair the complex deformity. During the procedures, we divided the complex operation into two parts: clitoral hood reduction using L-shaped incision and then labiaplasty using L-shaped edge resection. We describe the details of the method step-by-step and evaluate the treatment outcomes. A total of 38 sides (14 bilateral procedures and 10 unilateral procedures) of clitoral hood reduction and labiaplasty were performed. There were no wound healing complications in any cases. One patient had a secondary corrective operation for obvious asymmetry of bilateral labia minora. Ultimately, all the patients were satisfied with the cosmetic appearance and did not have complaints. The surgical procedure we describe proved to be an effective, simple method for dealing with the complex situation of hypertrophy of labia minora combined with clitoral hood protrusion. Subsequent L-shaped edge resection of labiaplasty is appropriate for individuals with darker skin, in particular.Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Genital Surgery.

Objective The miroRNA-21 (MiR-21) plays a vital role in the process of proliferation and apoptosis in different types of cells. EGF could increase the miR-21 primary transcript during adipose derived stem cells (ADSCs) differentiation, however, the underlying molecular mechanism is unclear. We hypothesized that EGF affects the proliferation and apoptosis of ADSCs by regulating miRNA-21. Methods Gain or loss of function strategy was used through transfecting ADSCs with chemically synthesized oligonucleotides complementary to miR-21. Profiles of post-transfection miR-21 caused by EGF were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Apoptosis of ADSCs was evaluated with flow cytometry. The expression levels of miR-21's targeted genes PTEN and FASLwere determined by Western blot assay. Results In response to miR-21 mimics or inhibitor, the apoptosis and cytoactivity of ADSCs changed correspondingly. Change of miR-21 expression level was checked and an inverse correlation of EGF was observed with PTEN and FASL expression in ADSCs. Conclusion Our results indicated that miR-21 could influence EGF expression and furtherly inhibits the apoptosis of ADSCs by downregulating PTEN and FASL. These findings may provide clues toward regulating biological activity of ADSCs with miR-21.

RationaleChondrosarcoma is a malignant mesenchymal tumor originating from cartilage. The pelvis, ribs, femur, and humerus are the most frequently affected sites, and scapula involvement is relatively rare. The aim of the present study was to report a case of chondrosarcoma in the scapula.Pat

Rationale Absence of the penis, known as aphallia, is a very rare congenital anomaly. It is believed to be a result of either the absence of the genital tubercle or its failure to fully develop and is associated with the level of hormones and chromosomal rearrangements. The failure of the genital tubercle influences the development of the penis and partly depends upon testosterone secreted by Leydig cells of the testis. Chromosomal polymorphisms may affect the functions of protection and regulation, potentially leading to susceptibility to congenital diseases. Herein, an extremely rare case of a congenital absence of the penis is described. Patient concerns A 3-month-old was brought to the OPD by his parents with complaints of absence of penis since birth and urine being passed rectally. When he was born, he was registered as a boy because his chromosomes were 46XY but with 9qh+. Local examination revealed the total absence of the penis. The scrotum was well developed. The testes were palpable bilaterally. The anal opening was located normally. No urethral orifice could be identified. However, his parents had not yet decided whether to accept treatment. The child has been lost to follow up. Diagnosis Congenital absence of the penis (aphallia) (46 XY normal male karyotype). Interventions We explained the nature of the abnormality and management options to the parents. However, it was much regretted that the patient was too young to make a decision and that his parents had not made a decision yet. They left without any further contact. Outcome Because the parents left our hospital without any contact, it has not been possible to develop a follow-up plan. Lessons In consideration of the rarity and devastating psychosocial consequences of this case, we accordingly call for active cooperation with doctors to minimize the negative impact of this malformation. Early assignment of gender avoids confusion and contradiction. Parental confidence solidifies the child's own confidence in his or her gender.

RATIONALE Abdominal aortic aneurysm is one of the most common aneurisms. Patients presenting with secondary back pain should be given prompt medical attention. Herein, a rare case of a giant abdominal aortic aneurysm that was successfully treated with surgery is described. PATIENT CONCERNS A 33-year-old Chinese male suffered from Marfan syndrome combined with giant abdominal aortic aneurysm, and presented with back pain, fever, nausea, vomiting, abdominal distention, and constipation. After undergoing numerous tests, the patient underwent an abdominal aortic aneurysm resection coupled with artificial graft bypass. The patient's recovery was smooth, and he was discharged 14 days after the operation in stable condition. DIAGNOSIS Abdominal aortic aneurysm. INTERVENTIONS The patient underwent a surgery involving mass resection and artificial graft bypass. OUTCOME The patient was discharged 14 days after surgery in stable condition. LESSONS Giant abdominal aortic aneurysms are rarely seen, and aneurysmectomy associated with prosthetic vascular graft repair is an effective and standard treatment for such aneurysms.

Rationale Desmoplastic fibroma (DF) is a rare, locally invasive but benign bone tumor. It represents one of the rarest bone diseases, with an incidence of only 0.11% of all primary bone tumors. Patient concerns Herein, a case of massive and unusual DF, with simultaneous involvement of ilium and ischium, is described. A 29-year-old man suffered minor pain in his right hip for 2 years. It worsened after sudden movements, which prevented him from walking normally. Physical examination showed a limitation when the right hip was flexed and a percussion pain on the hip region. A medical imaging examination showed that the right ilium and ischium had a massive bone lesion. The top of acetabular had very little bone left and a fracture was likely at any time. No prominent body weight loss was noted, because there was no extensive invasion to the adjacent soft tissue. Diagnoses DF of the Ilium and Ischium. Interventions The patient underwent a surgery involving curettage and grafting to maintain the stability of the pelvis. Outcomes The definitive pathological diagnosis was DF, without evidence of malignancy. The postoperative recovery course at 3-month follow-up was uneventful. Lessons To the authors' knowledge, such a massive DF involving both ilium and ischium has been rarely reported. Young patients require appropriate and timely treatment modalities.