Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Objective:Using atenolol as a model drug,the aim of this study was to develop a sustained and controlled transdermal drug delivery system(TDDS)based on polyethyleneimine-modified MoS2 nanoparticles(PEI-MoS2 NPs)that were responsive to near infrared(NIR)laser irradiation.Methods:The three-dimensional flower-like PEI-MoS2 NPs were successfully synthesized and further characterized by attenuated total reflection Fourier transform infrared spectroscopy,X-ray diffraction measurements,scanning electron microscopy,and transmission electron microscopy.The controlled release capacity of PEI-MoS2 NPs was examined using in vitro drug release and skin penetration experiments.Results:The PEI-MoS2 NPs exhibited a drug loading efficiency of 53.86% and high photothermal conversion ability.Moreover,the release of atenolol was enhanced by NIR stimulation with an enhancement ratio of 1.56.Conclusion:NIR-controlled PEI-MoS2 NPs was essential for the control and sustained release of drugs in TDDS.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective: To study the association between eating at night and skipping breakfast with college students anxiety symptoms, and to provide reference basis for preventing and alleviating college students anxiety symptoms. Methods: A cross sectional survey was conducted among 9 960 freshman from three universities in Kunming and Dali, Yunnan Province. The dietary frequency questionnaire was used to evaluate the dietary behavior of college students. The Depression Anxiety Stress Scale-21 (DASS-21) was used to evaluate the anxiety symptoms of college students. The association of late night snack and breakfast skipping with the association of anxiety symptoms in college students used generalized linear model and Logistic regression model. Results: The proportion of college students who reported eating at night and breakfast skipping in the last month was 72.5%(7 217/9 960) and 61.6%(6 131/9 960) respectively. The detection rate of anxiety symptoms in college students was 28.9%(2 875/9 960). There was a statistical significance between eating at night with anxiety symptoms( OR =1.40-2.54), and breakfast skipping with anxiety symptoms( OR =1.23-1.60)( P <0.05). The interaction between eating late at night and breakfast skipping was positively correlated with college students anxiety symptoms (multiplicative interaction, β=0.06, 95%CI=0.02- 0.10 , P<0.01; additive interaction, OR=2.00, 95%CI=1.59-2.51, P <0.01). Conclusion The study suggests that the college students who eat at night and frequently skipped breakfast are more likely to have anxiety symptoms. It suggested to promote the formation of healthy eating habits of college students, so as to reduce the occurrence of anxiety sympotoms.

【Objective】 To investigate the independent risk factors of urinary tract infection (UTI) in recipients under-going renal transplantation of donation after brain death (DBD), so as to provide a theoretical basis for the prevention and control of postoperative UTI. 【Methods】 A retrospective study was conducted for recipients who received renal transplantation of DBD in our hospital during Jan.2021 and Dec.2021. The recipients were divided into the infection group (n=26) and non-infection group (n=74) according to the incidence of UTI 3 months after operation. The risk factors of UTI were identified with univariate and multivariate analyses. 【Results】 The incidence of UTI was 26%. Univariate analysis showed that gender, postoperative urinary fistula, time of indwelling catheter and time of indwelling double J tube were the influencing factors of UTI (P<0.05). Forward stepwise regression analysis showed time of indwelling double J tube (OR=1.086,95%CI:1.003-1.177,P=0.042) and time of indwelling catheter(OR=4.687,95%CI:2.064-10.645, P<0.010) were the independent risk factors of UTI (P<0.05). 【Conclusion】 The time of indwelling catheter and time of indwelling double J tube are the independent factors of UTI after renal transplantation of DBD.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Biliary tract cancers(BTC),including gallbladder cancer and cholangiocarcinoma,has the characteristics of low early diagnosis rate,complex anatomy,insensitivity to radiotherapy and chemotherapy, and poor prognosis.In recent years,immunotherapy as a new method,has made great progress in the treatment of advanced malignant tumors.Immunotherapy is gradually applied in the treatment of BTC,such as inhibitory agents targeting the immune checkpoint receptor pathway,adoptive immunotherapy and tumor vaccines.

Biliary tract cancers(BTC),including gallbladder cancer and cholangiocarcinoma,has the characteristics of low early diagnosis rate,complex anatomy,insensitivity to radiotherapy and chemotherapy, and poor prognosis.In recent years,immunotherapy as a new method,has made great progress in the treatment of advanced malignant tumors.Immunotherapy is gradually applied in the treatment of BTC,such as inhibitory agents targeting the immune checkpoint receptor pathway,adoptive immunotherapy and tumor vaccines.