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

Objective To investigate the effect of circ_0114427 on apoptosis and inflammation of alveolar epithelial cells induced by lipopolysaccharide (LPS) and its mechanism. Methods Human alveolar epithelial cells were cultured in vitro and transfected with si-circ_0114427, microRNA (miR)-330-5p mimics or co-transfected with si-circ_0114427 and anti-miR-330-5p, and the cellswere then treated with 10 mg/L LPS for 24 hours. The expression levels of circ_0114427 and miR-330-5p in the cells were detected using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The protein levels of Cleaved-caspase3 and Cleaved-caspase9 were evaluated using western blot. Enzyme-linked immunosorbent assay (ELISA) was used to assess the expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Cell apoptosis was analyzed using flow cytometry. The interaction between circ_0114427 and miR-330-5p was validated using a dual luciferase reporter assay. Results After LPS treatment of alveolar epithelial cells, the expression of circ_0114427 was upregulated, while miR-330-5p expression was downregulated in in the cells (P < 0.05). Knockdown of circ_0114427 or upregulation of miR-330-5p could inhibit LPS-induced apoptosis, Cleaved-caspase3, Cleaved-caspase9, IL-6, and TNF-α levels in alveolar epithelial cells (P < 0.05). Circ_0114427 directly interacted with and negatively regulated miR-330-5p. Downregulation of miR-330-5p reversed the inhibitory effect of circ_0114427 knockdown on LPS-induced cell apoptosis and inflammation. Conclusion Knockdown of circ_0114427 can inhibit LPS-induced apoptosis and inflammation in alveolar epithelial cells, possibly through upregulation of miR-330-5p.

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 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.

Objective:To explore the strategies and complications of the submucosal tunneling endoscopic resection (STER) in the treatment of esophageal duplicated cyst (EDC).Methods:From January 2013 to December 2019, at Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, the clinical data of 11 hospitalized patients with EDC diagnosed by pathological examination who underwent STER were collected. The clinical featured, computed tomography (CT) findings, endoscopic findings, postoperative efficacy, complications and pathological results after operation were summarized.Results:Among the 11 patients, there were 6 males and 5 females, the age ranged from 13 to 67 years, and the mean age was (43.0±18.2) years. One case presented with swallowing obstruction, 1 case with belching, 4 cases with upper abdominal pain, and the remaining 5 cases had no specific clinical symptoms. Under endoscopy, the lesions of 11 patients were hemispherical or mound-shaped with smooth surface submucosal masses in the esophageal cavity, which were soft to touch. Under endoscopic ultrasonography, they all appeared as hypoechoic masses with clear boundary located in the esophageal muscularis propria. The results of CT scan of 9 patients showed round low-density cystic masses, among them 7 cases showed mild enhancement. The maximum diameter of the cysts was 1.5 to 4.4 cm, with mean maximum diameter being (2.8±0.8) cm, and the maximum diameter of most patients (7 cases) were 2 to 3 cm. The other two patients showed only slightly thickened esophageal wall on CT. Five lesions occurred in the horizontal mediastinum of the lower esophagus. All the 11 patients underwent STER operation successfully, among them 6 patients received simple STER and the cysts were completely resected, and the other 5 patients received STER and cauterization with argon ion for the residual cyst wall. The pathological results after operation indicated that 6 cases were congenital esophageal cysts and 5 cases were bronchogenic cysts. The median follow-up time (range) of 11 patients was 42 months (12-86 months). Ten patients recovered well after the operation, and local recurrence, malignant transformation or metastasis were not found. One case had recurrence, and was treated with STER and cauterization with argon ion for residual cyst wall and cured. No complications such as bleeding, fistula, mediastinal infection or death occurred during and after operation in all the 11 patients.Conclusions:STER is a minimally invasive, safe and effective treatment for EDC, and may be a new treatment for EDC.

Hepatocellular carcinoma has a low early diagnostic rate, and there is a lack of highly sensitive and specific tumor markers. In recent years, fluid biopsy technique, represented by circulating free DNA (cfDNA), has become an auxiliary method for the diagnosis of cancer and has attracted more and more attention due to its advantages of noninvasiveness, convenience, and repeatability. With reference to the recent studies in China and foreign countries, this article summarizes and analyzes the advances in cfDNA in the diagnosis and treatment of hepatocellular carcinoma from the aspects of biological characteristics, detection techniques, and clinical application, so as to provide a basis for clinical diagnosis and treatment.

In previous studies, we found that truncated rotavirus VP4* (aa 26-476) could be expressed in soluble form in Escherichia coli and confer high protection against rotavirus in the mouse mode. In this study, we further improved the immunogenicity of VP4* by polymerization. The purified VP4* was polymerized through incubation at 37 ℃ for 24 h, and then the homogeneity of the particles was analyzed by HPLC, TEM and AUC, while the thermal stability and antigenicity was analyzed by DSC and ELISA, respectively. Finally, the immunogenicity and protective efficacy of the polymers analyzed by a mouse maternal antibody model. The results showed that VP4* aggregated into homogeneous polymers, with high thermostability and neutralizing antibody binding activity. In addition, VP4* polymers (endotoxin <20 EU/dose) stimulated higher neutralizing antibodies and confer higher protection against rotavirus-induced diarrhoea compared with the VP4* trimers when immunized with aluminium adjuvant. In summary, the study in VP4* polymers provides a new strategy for the development of recombinant rotavirus vaccines.
Animals ; Antibodies, Viral ; Antigens, Viral ; Capsid ; Capsid Proteins ; Mice ; Polymerization ; Rotavirus ; Rotavirus Infections

Conservation of Natural Resources ; Hypocreales ; isolation & purification ; Medicine, Chinese Traditional ; Natural Resources ; Species Specificity ; Tibet