The thought of the way of heaven is the core philosophy of the Book of Changes， aiming to achieve the “pursuing good fortune and avoiding disaster” of human affairs or “seeking benefits and avoiding harm” in technology. The embedded value orientations， such as “continuous life”， “utmost sincerity”， and “correct desire”， provide ethical considerations for “seeking benefits and avoiding harm” in human gene editing technology. Among them， the thought of “continuous life” affirms the potential value of gene editing technology for human reproduction， diagnosis and treatment， or prevention of diseases and disabilities from two aspects of human reproduction and individual body and mind， while adopting a cautious attitude towards the risks of technology. The thought of “utmost sincerity” advocates that gene editing should be studied and applied following objective laws. The thought of “correct desire” puts forward the norm of human desire in human gene editing. In terms of the issue of offspring autonomy， the thought of the way of heaven provides some ethical support for parents to implement gene editing for their offspring for the sake of the offspring’s physical and mental development. In conclusion， the application of the thought of the way of heaven in the Book of Changes hopes that human gene editing technology will benefit mankind and provide it with broader prospects and a better future.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes.Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder.However,its therapeutic dosage closely approaches toxic levels.Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L,typically giving rise to gastrointestinal and central nervous system reactions.Cardiac toxicity is rare but serious in cases of lithium poisoning.The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers.This resulted in symptoms such as arrhythmia,shock,impaired consciousness,and coarse tremors.Following symptomatic supportive treatment,including blood dialysis,the patient's physical symptoms gradually improved.It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

【Objective】 To investigate the frequency of platelet antibodies in voluntary blood donors and patients in Zhongshan, Guangdong Province, and to study the specificity and cross-matching of platelet antibodies. 【Methods】 Platelet antibodies of blood donors and patients were screened by solid-phase immunoadsorption (SPIA), rechecked by flow cytometry (FCM), and antibody specificity was identified by PakPlus enzyme immunoassay, and platelet cross-matching was simulated by SPIA. 【Results】 A total of 1 049 blood donor samples and 598 patient samples were tested, with 6 (0.57%) and 49 (8.19%) samples positive for SPIA,respectively(P<0.05); In SPIA positive samples, the positive concordance rate of FCM in blood donors and patients was 100% vs 95%, and that of enzyme immunoassay was 100% vs 88%. Among the initial screening positive samples of blood donors, 5 were anti-HLA Ⅰ antibodies, accounting for 83%, and 1 was anti CD36 antibody, accounting for 17%, with an incidence rate of 0.10%. Among the 14 samples of enzyme immunoassay positive patients, 2 were anti-GP Ⅱb/Ⅲa, 1 was anti-GP Ⅱa/Ⅱa, 8 were anti HLA Ⅰ, and 3 were mixed antibodies (HLA Ⅰ, GP Ⅱb/Ⅲa, GP Ⅰa/Ⅱa). According to the types of antibodies, HLA Ⅰ antibodies were the most common, accounting for 65% (11/17), followed by HPA related anti GP, accounting for 35% (6/17). The majority of patients had a platelet antibody positive typing rate below 30%, accounting for 71.4% (10/14). 【Conclusions】 The positive rate of platelet antibody of patients in Zhongshan area is significantly higher than that of voluntary blood donors, and most of them are anti-HLA Ⅰ and anti-GP, and the incidence of anti-CD36 is extremely low. Therefore, it is necessary to establish a known platelet antigen donor bank, and at the same time, carry out platelet antibody testing and matching of patients, which is helpful to solve the issue of platelet transfusion refractoriness.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment

【Objective】 To study the incidence and specificity of platelet antibody in blood donors in Suzhou, analyze the distribution characteristics of platelet antibody in blood donors in this area, and explore the significance of platelet antibody detection in blood donors to reduce the adverse reactions toplatelet transfusion in clinical. 【Methods】 Platelet antibody detection was performed in 2178 blood donors in this area by solid-phase immunosorbent assay. The antibody specificity of the positive samples was analyzed by commercial kit, and the anti-CD36 antibody positive samples were further identified by flow cytometry and gene sequencing. 【Results】 Twelve positive samples were detected by platelet antibody screening, with a positive rate of 0.55%(12/2 178), including 5 males (0.33%, 5/2 178)and 7 females(1.06%, 7/2 178). Among the positive samples, anti-HLA-Ⅰ antibody was identified in 2 cases, anti-CD36 antibody in 1 case, and the antibody specificity was not identified in the other 9 cases. In one case, the positive rate of anti-HLA-Ⅰ antibody PRA was 31.31%(31/ 99), which was mainly specific to anti-B15, anti-B35 and anti-B40. The positive rate of anti-HLA-Ⅰ antibody PRA in the other case was 45.45%(45/ 99), which was mainly specific to anti-A2, anti-A11, anti-A24, anti-A29, anti-A33, anti-A66, anti-B15 and anti-B35. The blood donor with anti-CD36 antibody was type I CD36 deficiency, and 329_330delAC mutation occurred in exon 5. 【Conclusion】 Through antibody screening and specificity identification, the positive rate of platelet antibody in females was significantly higher than that in males(P<0.05). In addition to the common anti-HLA-I antibodies, anti-CD36 antibody was also detected in type I CD36 deficient blood donor. Therefore, the detection of platelet antibodies in blood donors is of certain clinical significance to reduce the adverse reactions to blood transfusion caused by antibodies in platelet products.

[Abstract] Objective: To investigate the effect and mechanism of miR-449b-5p on the proliferation of ovarian cancer cells. Methods: Cancer tissue and corresponding para-cancerous tissue specimens from 20 patients who underwent surgery in the Department of Obstetrics and Gynecology of Sichuan Provincial People's Hospital from June 2018 to June 2020 were collected for this study; in addition, normal ovarian epithelial cell line (HOSEpiC) and six human cervical cancer cell lines (SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780) were also selected. mRNA expressions of miR-449b-5p and CCNE2 in ovarian cancer tissues and cells were detected by qPCR. The plasmids miR-NC, miR-499b-5p mimic, miR-499b-5p inhibitor and pc-CCNE2 were transfected into SKOV3 cells separately or in combination. Cell growth and cell cycle were measured by the CCK-8 method and Flow cytometry, the expression of CCNE2 protein was detected by WB assay, respectively. The targeting relationship between miR-449b-5p and CCNE2 was verified by Dual luciferase reporter assay. miR-499b-5p transfected SKOV3 cells were injected subcutaneously in nude mice to construct xenograft model, and the tumor volume was measured weekly. Nude mice were sacrificed at day 42. The weight of the subcutaneous tumors was weighed by an electronic balance, and the expressions of CCNE2 and Ki67 were detected by immunohistochemistry. Results: Compared with normal ovarian tissues and epithelial cell line HOSEpiC, miR-499b expression was significantly downregulated in human cervical cancer tissues and cell lines SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780 (P<0.01). Compared with the Control group, the proliferation of SKOV3 cells in the miR-499b mimic group was significantly reduced (P<0.01) and the cell proportion in G0/G1 phase was significantly increased ( P<0.01); while the proliferation of SKOV3 cells in the miR-499b inhibitor group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Over-expression of miR-499b-5p significantly inhibited the luciferase activity of wild type CCNE2 plasmid (P<0.01) but had no effect on the luciferase activity of the mutant CCNE2 plasmid. Compared with the miR-499b mimic group, the growth of SKOV3 cells in the miR-499b mimic+pc-CCNE2 group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Compared with the miR-NC group, the tumor volume and weight of nude mice in the miR-499b mimic group were significantly reduced (all P<0.01), and the proportion of CCNE2 and Ki67 positive cells was significantly decreased (P<0.01). Conclusion: miR-449b-5p inhibits the growth and cell cycle progression of ovarian cancer cells by targeting Cyclin E2.

【Objective】 To investigate the expression of CD36 antigen in Suzhou area, analyze the type of antigen deficiency and gene mutation, so as to provide references for the establishment of CD36 negative donor registry in Suzhou. 【Methods】 Anticoagulant whole blood samples (805 cases) were randomly collected from healthy blood donors in Suzhou Blood Center. The expression of CD36 antigen on platelet and monocyte was analyzed by flow cytometry to determine the type of CD36 deficiency. The gene mutation type of platelet CD36 antigen-deficient was performed by genomic DNA sequencing. 【Results】 The CD36 deficiency frequency on platelet was 2.48% (20/805), among which TypeⅠ(lacking CD36 expression both on platelet and monocyte) and TypeⅡ(lacking CD36 expression on platelet only) CD36 deficiency accounted for 10% (2/20) and 90% (18/20), respectively. CD36 gene mutations were found in 10 samples, including 3 cases of 329_330 d^elAC, 1 case of 1228_1239 d^elATTGTGCCTATT and 2 cases of 1163 A>T; 1 case of 329_330 d^elAC+ 1172_1183 d^elTATTGGTCAAGC and 287 G>C+ 329_330 d^elAC heterozygous mutation. In addition, 1 case of 745 A>G and 1 case of 806 C>T mutations were novel, and not yet reported. 【Conclusion】 Results showed that the frequency of CD36 antigen deficiency in Suzhou were similar to that reported in southern China, but the mutation sites were slightly different. The establishment of CD36 negative platelet registry could provide negative platelets for patients with transfusion reactions caused by anti-CD36 antibody and improve the effect of clinical platelet transfusion.

Yuanhuacine is a daphne-type diterpene isolated from Daphne genkwa. It is also isolated from the plant of Daphne and Euphorbia. With the further research on yuanhuacine, it has been found that yuanhuacine has strong anti-tumor activity, and it also exhibits significant anti-virus, anti-inflammatory, neuroprotective and anti-fertility activities. Yuanhuacine can enter various tissues with the blood, and pass through the blood-brain barrier. The bioavailability of yuanhuacine is good, which has potential therapeutic significance for the lesions of all tissues. However, the researches on yuanhuacine mainly focus on the preclinical research and yuanhuacine is only used to induce labor clinically. The purpose of this study is to systematically summarize and analyze the pharmacological activity, drug metabolism in vivo, and clinical application of yuanhuacine, so as to provide a theoretical basis for its development and application.

Objective To explore the effect of applying surface neuromuscular electrical stimulation (NMES) on the functioning of the upper esophageal sphincter (UES) using the high-resolution solid-state manometry.Methods Seventeen healthy volunteers were selected and given sham stimulation (SS),superior and inferior hyoid stimulation (SIHS),superior hyoid stimulation (SHS) or inferior hyoid stimulation (IHS) at a frequency of 80 Hz and the maximum tolerated level before swallowing.Any changes in the kinematics or biomechanics during swallowing and at rest were recorded using high-resolution solid-state manometry.One-factor repeated analysis of the measurement variance was used.Results A significant decrease in the duration of UES relaxation was observed in response to the electrical stimulation (compared with the sham stimulation).The UES's residual pressure showed a rising trend during electrical stimulation,especially in response to IHS,but the difference compared with SS was not significant.The UES's resting pressure during SIHS increased significantly compared with SS,but there was no significant difference between SHS and IHS in this respect.Conclusions Surface neuromuscular electrical stimulation applied to the neck can immediately change the functioning of the UES.NMES at the maximum tolerated intensity can reduce the duration of UES relaxation,which is important for dysphagia therapy and research.