Objective To prepare a biodegradable sckeral implant containing triamcinolone-acetonide-acetate(TAA) and polylactic acid(PLA) and investigate its release in vitro.Methods The TAA-PLA implant was prepared by melt-extrude technique.The drug release of TAA in vitro was determined by high performance liquid chromatography(HPLC).Results The implant was white pillar with 8 mm in length,8 mg in weight,and 0.8 mm in diameter.The drug loading was 30%.The drug was released at a steady and slow rate.Its accumulation release rate is 75.84% on the 30th day.Drug release profile in vitro was in accordance with Higuchi equation Q=0.137(t-0.752)1/2.Conclusion A sleral implant containing TAA-PLA is prepared,which has the evident feature in delaying the release of TAA and is biological degradable.It might be a novel vehicle for the topical use of TAA.

Objective To discuss the differential diagnostic value of confocal laser endomicroscopy (CLE)for benign and malignant non-protruding gastric lesions.Methods A total of 37 patients with nonprotruding gastric lesions diagnosed by conventional gastroscopy underwent CLE.Fluorescein sodium was intravenously injected,and target biopsy was obtained.Malignant lesionss diagnosed with CLE or biopsy were treated by endoscopy or surgery.Patients with benign lesions were give routine medication and followed up every 3 months until the lesions were cured.Results CLE diagnosed 11 malignant and 26 benign lesions.However,1 of 11 cancers was confirmed as benign by histopathology,while 1 of 26 benign lesions was confirmed cancer.Lesions in 12 patients were resected,with 3 by endoscopy,and 9 by surgery,and findings of post-operative pathology were consistent with those of target biopsy.No malignancy was found during the follow-up of benign lesions,and all lesions were healed after 3.16(3.58 ± 1.20)months.The sensitivity,specificity,and accuracy of CLE in diagnosis of malignant non-protruding gastric lesion were 90.9％,96.2％,and 90.9％,respectively.The positive and negative predictive values were 90.9％ and 96.2％,respectively.The Kappa value of CLE and histopathology was 0.871.Conclusion CLE is of significant value for the diagnosis of non-protruding gastric lesions,and may replace biopsy in real-time histological diagnosis.

The study was aimed to investigate the optimum conditions of freeze drying preservation of amniotic membrane (AM). The AM from the health puerperal woman was preserved by freeze drying at optimized way. The key factors of freeze drying process, including abstersion aqua, conservation liquor, the curve of freezing temperature, and the ingredient of protective agent, were optimized. All their morphologic structure was observed by light microscope and scanning electron microscope. The degradation rates by collagenase IV and the characterization of biomechanics were analyzed. The radio-immunologic method was used to investigate the cytokines quantity. All properties of freeze dried AM were compared with those of fresh AM. Light micrographs showed that the five structure-layers exist both in the fresh AM and in those preserved by freeze drying, while the fibro-material was tight-structured in the fresh AM, but loose slightly; the thickness of fibro-material was larger slightly in freeze dried AM. Scanning electron micrographs show that the micro-hairs of epithelial cells in fresh AM were decreased slightly in optimized drying AM, the collagen fibre of fresh AM and of optimized drying AM were well in morphological structures and arranged tightly. The degradation rate by collagenase IV was faster in optimized drying AM,compared with that of the fresh AM. There were insignificant diversity in biomechanical characters (tensile strength, elongation at break and elastic modulus) of the optimized drying AM compared with fresh AM. The cytokines quantity in optimized drying AM decreased significantly compared with fresh AM. The improved freeze drying process has better advantage in keeping the morphological structure, preferable biomechanics and biological vitality of AM, compared with the early research.
Amnion ; metabolism ; ultrastructure ; Biomechanical Phenomena ; Collagenases ; metabolism ; Cytokines ; metabolism ; Female ; Freeze Drying ; methods ; Humans

OBJECTIVETo evaluate the clinical efficacy of YANG's pricking-cupping therapy for knee osteoar thritis (KOA). Methods This was a multi-center randomized parallel controlled trial. One hundred and seventy one patients with KOA were randomly allocated to a pricking-cupping group (89 cases) and a conventional acu puncture group (82 cases). Neixiyan (EX-LE 4), Dubi (ST 35) and ashi points were selected in the two groups. Patients in the pricking-cupping group were treated with YANG's pricking-cupping therapy; the seven-star needles were used to perform pricking at acupoints, then cupping was used until slight bleeding was observed. Patients in the conventional acupuncture group were treated with semi-standardized filiform needle therapy. The treatment was given for 4 weeks (from a minimum of 5 times to a maximum of 10 times). The follow-up visit was 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analogue scale (VAS) were adopted for the efficacy assessments.

RESULTSThe pain score, stiffness score, physical function score and total score of WOMAC were all reduced after 4-week treatment and during follow-up visit in the two groups (all P<0. 0001). Except that the difference of stiffness score between the two groups was not significant after 4-week treatment (P>0. 05), each score and total score of WOMAC in the pricking-cupping group were lower than those in the conventional acupuncture group after 4-week treatment and during follow-up visit (P<0. 0001, P<0. 01). After 2-week treatment, 4-week treatment and during follow-up visit, the VAS was all reduced compared with that before treatment (all P<0. 0001) ; with the increase of the treatment, the reducing trend of VAS was more significant (P<0. 0001). The scores of VAS in the pricking-cupping group were lower than those in the conventional acupuncture group after 4-week treatment and during follow-up visit (P < 0. 01, P <0. 0001). CONCLUSION The YANG's pricking-cupping and conventional acupuncture therapy can both significantly improve knee joint pain and function in patients with KOA, which are relatively safe. The pricking cupping therapy is superior to conventional acupuncture with the identical selection of acupoints.

Acupuncture Therapy ; Adult ; Aged ; Arthralgia ; physiopathology ; therapy ; Combined Modality Therapy ; Female ; Humans ; Knee Joint ; physiopathology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Osteoarthritis, Knee ; physiopathology ; therapy ; Treatment Outcome

Chimeric antigen receptor T cell(CAR-T)therapy has produced remarkable results in the treatment of hematological tumors.The BCMA antigen is widely expressed on the surface of multiple myeloma cells and is a suitable,efficient target for CAR-T therapy.BCMA CAR-T cell therapy has a high response rate for relapsed or refractory patients in particular,and CAR-T cells are still detectable in most patients 1 year after infusion.However,drug resistance and disease recurrence remain key problems in clinical management.In this paper,we discuss the response factors and resistance induction mechanism of BCMA CAR-T cell therapy from several perspectives,such as the immune es-cape of multiple myeloma cells,CAR-T product factors,previous treatment regimens,and tumor immune microenvironment inhibition.We also propose possible optimization strategies in order to provide reference for future exploration.

Objective To explore and evaluate the economy of pembrolizumab combined chemotherapy in the first-line treatment of advanced malignant pleural mesothelioma from the perspective of China's healthcare system,and to provide pharmacoeconomic evidence and reference for clinical medication and related health decisions.Methods A partition survival model was constructed based on the IND227 study data,with 21 d as the model period and simulated to 99％of patients died.The model output index was the quality-adjusted life year(QALY).The cost-utility analysis was used to evaluate the economics of combination chemotherapy for advanced malignant pleural mesothelioma by chemotherapy alone.Further,the robustness of the basic analysis results was proved by univariate sensitivity analysis and probabilistic sensitivity analysis.Results The results of basic analysis showed that compared with chemotherapy alone,the incremental cost-utility ratio(ICUR)of pembrolizumab combined with chemotherapy was 1 447 296.58 yuan/QALY,which was greater than 3 times China's per capita GDP(268 074 yuan/QALY)in 2023 as the willingness-to-pay(WTP)threshold,which was not economical.In the case of receiving charity drug donations,the ICUR was 102 236.18 yuan/QALY,which was below the WTP threshold.The results of univariate sensitivity analysis showed that the cost of pembrolizumab,utility discount rate and supportive therapy in the chemotherapy group had more significant effects on the results.The results of the probability sensitivity analysis showed that the basic analysis results showed good robustness.Conclusion At a WTP threshold of 3 times China's per capita GDP in 2023,pembrolizumab combined with chemotherapy is not cost-effective for treating advanced malignant pleural mesothelioma.However,if the patient receives charity donations,combination of pembrolizumab and chemotherapy is more cost-utility.

MicroRNAs (miRNAs) are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.
Animals ; Dendrites ; genetics ; metabolism ; Dendritic Spines ; genetics ; metabolism ; Down-Regulation ; physiology ; Methyl-CpG-Binding Protein 2 ; biosynthesis ; genetics ; MicroRNAs ; genetics ; metabolism ; Rats