1.Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy.
Siqin HE ; Lulu WANG ; Dongxu WU ; Fan TONG ; Huan ZHAO ; Hanmei LI ; Tao GONG ; Huile GAO ; Yang ZHOU
Acta Pharmaceutica Sinica B 2024;14(2):765-780
A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.
2.Risk Factors of Recurrence in Patients with Ischemic Stroke Treated with Aspirin Single Drug Antiplatelet Therapy
Qian LI ; Puqiong FENG ; Qin YAO ; Hanmei CHEN ; Ting ZHAO ; Hui WU
Journal of Kunming Medical University 2024;45(1):78-82
Objective To investigate the risk factors of relapse in patients with ischemic stroke using aspirin for single drug antiplatelet therapy.Methods A retrospective analysis was conducted on 200 patients with mild and medium ischemic stroke after 12 months of single drug treatment with aspirin,and the patients were divided into non-recurrence group and recurrence group according to the recurrence of stroke.Univariate analysis and multivariate logistic regression model were used to explore whether the related indicators were risk factors for recurrence.The ROC curve was used to predict the critical value of risk factors.Results Univariate analysis showed that platelet count,Hcy level and the A allele at rs12041331 site of PEAR1 gene were statistically significant risk factors(P<0.05).Multifactor analysis showed that the independent risk factor for recurrence was homocysteine level[OR = 1.16(1.089-1.240),P<0.001)].The critical value of ROC prediction was 8.35 μmol/L(sensitivity 0.847,specificity 0.532).Conclusions The Hcy level,platelet count and A allele at rs12041331 site of PEAR1 gene are risk factors for recurrence in patients with ischemic stroke treated with aspirin for Single drug antiplatelet therapy.Hcy level is independent risk factor and can be used to predict the risk of recurrence.
3.Effects of active ingredients of traditional Chinese medicine in the prevention and treatment of senile macular degeneration and the research progress of its ocular new drug delivery preparations
Yadi ZHU ; Wei LI ; Shuyao LI ; Hanmei LI ; Liang ZOU
China Pharmacy 2024;35(19):2432-2437
Senile macular degeneration(SMD) is a degenerative disease of the macular region of the eye that causes visual impairment in older people worldwide. It is the focus and difficulty of the treatment of ophthalmic diseases at home and abroad. This paper reviewed traditional Chinese medicine (TCM) active ingredients for the treatment and prevention of SMD, and its new ocular delivery preparations. Studies have shown that many active ingredients of TCM can inhibit the progression of SMD through various ways such as anti-oxidation, solid lipid nanoparticles, microemulsions/nanoemulsions, in-situ gel, etc. However, due to the low solubility, chemical instability and difficulty in overcoming the eye barrier of most TCM active ingredients, their clinical application in the treatment of SMD is seriously hindered. New preparations, such as liposomes, solid lipid nanoparticles, microemulsion/nanoemulsion, in situ gels, have good application prospects in ocular drug delivery.
4.Correlation study of pregnancy stress,pre-pregnancy health care behavior and coping style of pregnant women
Jingling LI ; Xiaoyan XU ; Jing LI ; Qian ZHOU ; Yi GAO ; Xuan ZHOU ; Ying SHUAI ; Hanmei LIU
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(8):968-974
Objective·To assess the levels of pregnancy-related stress,pre-pregnancy health care behaviors,and coping styles among pregnant women,analyze the influencing factors of pregnancy stress and provide insights for the management of pregnancy health in expectant mothers.Methods·A total of 265 pregnant women receiving treatment at the Obstetrics Clinic of the Affiliated Hospital of Zunyi Medical University from April to August 2022 were included as participants.General information questionnaires,pre-pregnancy health care behavior questionnaires,pregnancy stress scales and simple coping style questionnaires were utilized for data collection.After obtaining the consent of the patients,assessments on pregnancy stress levels,pre-pregnancy health care behaviors,and coping styles were conducted.Results·The overall average score for pregnancy stress among pregnant women was 1.05±0.41.Multiple linear regression analysis revealed that age,number of pregnancies,history of threatened abortion,fetal gender expectations,attending prenatal education classes or reviewing relevant manuals significantly influenced pregnancy-related stresses(P<0.05).The score of pre-pregnancy health care behavior was 10.09±2.63 with proportions indicating high-level,medium-level,and low-level adherence at 17.36%,54.34%,and 28.30%.In pregnant women,the total score for coping styles was 27.22±9.68,with a positive coping dimension score of 17.79±9.84 and a negative coping dimension score of 9.42±7.39.Pearson correlation analyses demonstrated a negative association between pregnancy-related stresses and pre-pregnancy health care behaviors(r=-0.313,P<0.01),and a negative correlation between pregnancy-related stresses and coping styles(r=-0.163,P<0.01),while a positive relationship existed between pre-pregnancy health care behaviors and coping styles(r=0.220,P<0.01).Conclusion·Pregnant women experience moderate levels of pressure during their pregnancies and have suboptimal engagement in preconceptional healthcare practices.Nursing staff should intensify efforts towards disseminating knowledge on preconceptional healthcare practices,thereby empowering women of childbearing age to actively acquire pertinent reproductive-health knowledge prior to conception so that minimizing adverse maternal-infant outcomes,optimizing maternal-infant healthcare strategies,and enhancing overall well-being can be achieved through these measures.
5.Clinical and immunoserological features of 35 cases of anti-p200 pemphigoid: a retrospective analysis
Suo LI ; Ke JING ; Yuan WANG ; Zhiliang LI ; Chenjing ZHAO ; Hanmei ZHANG ; Guirong LIANG ; Suying FENG
Chinese Journal of Dermatology 2024;57(10):897-903
Objective:To analyze clinical, immunoserological, and therapeutic features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to February 2024. Their clinical, immunoserological, and therapeutic characteristics were retrospectively analyzed.Results:A total of 35 patients were included, with a male-to-female ratio of 2.5∶1 (25 males and 10 females) and ages of 57.74 ± 17.12 years. Two (5.71%) patients were accompanied by psoriasis. In these patients, anti-p200 pemphigoid exhibited heterogeneous clinical phenotypes, mimicking classic bullous pemphigoid (20 cases, 57.14%), linear IgA bullous dermatosis (8 cases, 22.86%), or eczema (4 cases, 11.43%). The positive rates of direct immunofluorescence (DIF), indirect immunofluorescence on salt-split skin (ss-IIF), Western blot analysis with dermal extracts as substrates, and Western blot analysis with laminin γ1 C-terminal region (Lnγ1C) as substrates were 100% (24/24), 82.86% (29/35), 100% (35/35), and 80.64% (25/31), respectively. Among the 35 patients, treatment and follow-up information was available for analysis in 33. Six patients (18.18%) received non-glucocorticoid systemic therapy and topical glucocorticoid therapy, with a follow-up period ( M [ Q1, Q3]) of 19.50 (6.50, 69.25) months, and 1 withdrew the drugs. Sixteen patients received systemic glucocorticoids combined with traditional anti-inflammatory drugs, with a follow-up period of 13.50 (4.25, 18.00) months, the initial dose of glucocorticoids was equivalent to 0.30 - 0.50 mg·kg -1·d -1 of prednisone, and the time to disease control was 15.31 ± 5.23 days; among the 16 patients, 3 experienced fluctuations in disease condition which were alleviated by adding dapsone, and 1 discontinued glucocorticoids. Five patients (15.15%) received systemic glucocorticoids combined with immunosuppressants, with a follow-up period of 26.00 (14.00, 90.00) months, the initial dose of glucocorticoids was equivalent to 0.50 - 0.75 mg·kg -1·d -1 of prednisone, and the time to disease control was 10.20 ± 3.27 days; among the 5 patients, 2 received maintenance treatment with glucocorticoids (5 - 10 mg/d prednisone), 2 withdrew the drugs, and 1 relapsed after discontinuing glucocorticoids. One patient (3.03%) received systemic glucocorticoids combined with rituximab therapy, with a follow-up period of 53 months, and discontinued glucocorticoids thereafter. One patient (3.03%) received systemic glucocorticoids combined with dupilumab therapy, which proved to be effective. Four patients (12.12%) received systemic glucocorticoids combined with Janus kinase inhibitors, and 3 responded well. Conclusions:Anti-p200 pemphigoid presented a heterogeneous clinical profile in this series of patients, but scarring and milia were rare. Some patients showed negative results in Western blot analysis with Lnγ1C as substrates. The prognosis of anti-p200 pemphigoid was usually favorable, and most patients could achieve complete remission and ultimately discontinue medication.
6.Clinical and immunoserological features of 20 cases of epidermolysis bullosa acquisita
Yuan WANG ; Suo LI ; Zhiliang LI ; Ke JING ; Chao SUN ; Guirong LIANG ; Hanmei ZHANG ; Suying FENG
Chinese Journal of Dermatology 2024;57(10):904-909
Objective:To analyze clinical and immunoserological features of patients with epidermolysis bullosa acquisita (EBA) .Methods:Clinical data were collected from patients with confirmed EBA at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to January 2022, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:A total of 20 patients were collected, including 7 males and 13 females, and they were aged 41.85 ± 18.43 years. Ten patients presented with the classical phenotype of EBA, 8 with the inflammatory phenotype of EBA, and 2 with the mixed phenotype of EBA. Mucosal involvement occurred in 19 cases, nail involvement occurred in 4, scarring was observed in 9, and milia in 13. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side in 19 cases. Enzyme-linked immunosorbent assay for type Ⅶ collagen revealed positive results in 19 cases, with a diagnostic sensitivity of 95%. Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 290 000 in 16 cases, with a diagnostic sensitivity of 80%, and multiple autoantibodies against different basement membrane zone antigens were identified in 3 cases. Fifteen patients received systemic glucocorticoids, including 2 receiving combined immunosuppressive agents and 13 receiving combined anti-inflammatory agents with dapsone and colchicine as the first and second commonly used anti-inflammatory agents respectively; among 5 patients receiving non-glucocorticoid therapy, 2 with inflammatory EBA were sensitive to dapsone and colchicine, while the other 3 patients were lost to follow-up. Totally, 17 patients were followed up for an average duration of 26.21 months. Among the 17 patients, 1 achieved complete remission off therapy, 2 achieved complete remission on minimal therapy, and the remaining 14 patients achieved partial remission.Conclusions:The treatment of EBA is challenging, and anti-inflammatory agents such as dapsone and colchicine are often used. Immunoserological tests are of great value in the diagnosis of EBA.
7.Impact of cold circulation liquid temperature on ablation focus morphology of microwave ablation for porcine liver in vitro
Xia LUO ; Ping HE ; Xin YANG ; Juying ZHANG ; Qiong JIANG ; Linli FENG ; Hanmei LI ; Xiaoqing TANG ; You YANG ; Jinhong YU
Chinese Journal of Interventional Imaging and Therapy 2024;21(5):294-297
Objective To observe the impact of cold circulation liquid temperature on ablation focus morphology of microwave ablation(MWA)for in vitro porcine liver tissue.Methods Twenty in vitro fresh porcine liver blocks were randomly divided into ice water circulation group(group A)and normal temperature circulation group(group B),respectively.Ten target ablations in each subgroups in group A and group B,i.e.A1 and B1(50 W,1 min),A2 and B2(50 W,5 min),A3 and B3(60 W,1 min),A4 and B4(60 W,5 min),A5 and B5(70 W,1 min)as well as A6 and B6(70 W,5 min)subgroups were performed using different ablation power(50,60,70 W)and ablation time(1,5 min),respectively.Then the morphology indexes of ablation foci,including longitudinal diameter(LD),transverse diameter(TD),roundness index(RI)and volume(V)were compared between subgroups in group A and B,also among subgroups within group A and B.Results Under the same ablation power and time,LD of ablation foci in subgroups of group A were all smaller than those of group B(all P<0.05).Significant differences of RI of ablation foci were found between A1 and B1,A2 and B2,A4 and B4,A5 and B5 as well as A6 and B6 subgroups(all P<0.05),but not between A3 and B3 subgroups(P>0.05).However,the main effect of cold circulation liquid temperature on ablation focus TD(F=1.125)nor V(F=3.332)was not significant(both P≥0.05).Under the same cold circulation liquid temperature,significant differences of the morphology indexes of ablation foci were detected between A1 and A2,A3 and A4 as well as A5 and A6 subgroups,also between corresponding subgroups in group B(all P<0.05).Conclusion During MWA for in vitro porcine liver tissue under constant ablation power and time,taken ice water as the cold circulation liquid was benefit to ablation focus shaped spherically.With the extension of ablation time,the larger the ablation focus,the higher the RI.
8.Application of intelligent robot system in teaching cervical spine manipulation
Yuandong LI ; Hanmei BU ; Guang YANG ; Aifeng LIU ; Ping WANG ; Minshan FENG
International Journal of Biomedical Engineering 2023;46(4):336-341
Objective:To explore the application effect of an intelligent teaching robot system of lifting manipulation in cervical spine manipulation teaching.Methods:60 doctors were randomly divided into an experimental group ( n = 30) and a control group ( n = 30). The control group was taught by a certified chief physician using a combination of "PowerPoint presentations, video demonstrations, and operation demonstrations" . Each part is 5 min. The experimental group was taught by the intelligent teaching robot system with a spinning technique. The teaching time is 15 min for both groups. At the end of the two teaching sessions, the two groups were trained five times under different BMIs and passed the system assessment. The qualified rates of pre-traction force, lifting and pulling force, maximum force, pre-traction time, lifting and pulling time, rotation amplitude, and pitch amplitude were compared between the two groups. Results:In normal, there was significant differences between the qualified rates of pre-traction force, lifting and pulling force, maximum force, pre-traction time, lifting and pulling time, rotation amplitude, and pitch amplitude in two groups (all P<0.05). For overweight people, there were significant differences in pre-traction force, pulling force, maximum force, and rotation amplitude (all P <0.05), while there were no significant differences in pre-traction time, pulling time, or pitching amplitude (all P >0.05). In obesity, there were significant differences in pre-traction force, lifting and pulling force, maximum force, and pitch amplitude (all P <0.05), but no significant differences in pre-traction time, lifting and pulling time, or rotation amplitude (all P >0.05). Conclusions:The proposed system can improve the pass rate of spinning manipulation, especially by effectively controlling the pre-traction force, pulling force, and maximum force.
9.Suppressive effect of lignans from Euphorbia neriifolia L.on esophageal squamous cancer cell
Weiyan QI ; Chunlei XIA ; Roujin AN ; Xinmei Gao ; Dongping LI ; Hanmei XU
Journal of China Pharmaceutical University 2022;53(1):93-98
Eubhorbia neriifolia L. is a plant of Euphorbia family.Five known lignans were isolated from the aerial parts of E. neriifolia L. by silica gel for column chromatography and preparative high-performance liquid chromatography (HPLC).Their potential antitumor activities were evaluated in vitro.Compound 2 exhibited proliferation inhibition and cytotoxicity against esophageal squamous cancer cells, especially KYSE-410 and KYSE-450 cells.Further analyses showed that compound 2 could significantly induce apoptosis through the activation of caspase 3/9 and down-regulation of the Bcl-2/Bax protein ratio.These results suggested that compound 2 had a significant inhibitory effect on the esophageal squamous cancer cells, especially KYSE-410, which deserves further research as a potential antitumor agent.
10.Optimization of indirect immunofluorescence on salt-split skin and its application in detection of bullous pemphigoid antibodies
Yuan WANG ; Meiwen YU ; Ruiyu XIANG ; Suo LI ; Zhiliang LI ; Ke JIN ; Hanmei ZHANG ; Suying FENG
Chinese Journal of Dermatology 2022;55(1):12-15
Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.

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