OBJECTIVES: To investigate the protective effects and underlying mechanisms of Gynostemma pentaphyllum (GP)ethanol extract on motor dysfunction in a mouse model of Parkinson's disease (PD). METHODS: Eighty C57BL/6 male mice were randomly divided into five groups: control group, model group, levodopa group (positive control group), low-dose GP group, and high-dose GP group, with 16 mice per group. The PD model was induced by injection of 6-hydroxydopamine into the substantia nigra pars reticulata of the mice. Two weeks after 6-hydroxydopamine, positive control group received intraperitoneal injection of levodopa 10 mg·kg^－1·d^－1, while low-dose GP and high-dose GP groups received GP extract 100 or 200 mg·kg^－1·d^－1 orally for three weeks. After a 3-week-treatment, the effects of GP on motor dysfunction in 6-hydroxydopamine-induced PD were assessed using open field and CatWalk gait tests, while the effects on muscle strength were evaluated by forelimb grip strength. Immunofluorescence staining was used to detect the number of tyrosine hydroxylase (TH) positive neurons. The levels of dopamine and serotonin in the midbrain were determined by enzyme-linked immunosorbent assay. In addition, Western blotting was performed to detect the expression of mitogen-activated protein kinase (MAPK) family proteins such as p-extracellular signal-regulated kinase (ERK)1/2, p-p38 and p-c-Jun N-terminal kinase (JNK)1/2, and mitochondrial apoptosis pathway proteins such as B-cell lymphoma (Bcl)-2, Bcl-2 associated X protein (Bax), and cleaved-cysteine aspartic acid specific protease (caspase)-3. RESULTS: Behavioral experiments showed that GP significantly improved the spontaneous activity and motor coordination of PD mice (P<0.05). The forelimb grip strength was also increased by GP treatment (P<0.05), compared to the PD model group. In addition, compared with the model group, the number of TH-positive neurons in substantia nigra pars reticulata region, the levels of dopamine and serotonin in midbrain and the expression of p-ERK1/2 were significantly increased by GP treatment (all P<0.05), whereas the expression of p-p38 and p-JNK1/2, the ratio of Bax/Bcl-2 and cleaved-caspase-3/caspase-3 were significantly decreased (all P<0.05). CONCLUSIONS The results indicate that GP might increase dopamine and serotonin levels in the midbrain and promote the survival of dopaminergic neurons in substantia nigra pars reticulata by regulating the expression of phosphorylation of MAPK family proteins and the expression of mitochondrial apoptosis-related proteins, thereby ameliorating motor deficits in PD mice.
Animals ; Mice ; Male ; Gynostemma/chemistry* ; Mice, Inbred C57BL ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Parkinson Disease/metabolism* ; Disease Models, Animal ; Neurons/pathology*

Organoids are three-dimensional (3D) cellular structures formed through the differentiation and self-organization of pluripotent stem cells or tissue-derived cells, showing considerable potential in the research on disease mechanism, personalized medicine, and developmental biology. However, the development of organoids is limited by the complex composition, batch-to-batch variations, and immunogenicity of basement-membrane matrix in the current culture system, which hinders the clinical translation and in vivo applications of organoids. Hydrogels are highly hydrated 3D polymer network materials, with modifiable mechanical and biochemical properties by engineering, representing an ideal alternative to basement-membrane matrix. This article reviews the research progress in engineered hydrogels with defined composition currently used in organoid culture. We introduce the structural characteristics and engineering design considerations of hydrogels, emphasize the latest research progress and specific application cases, and discuss the future development of these engineered hydrogels, provide valuable insights for the further advancement and optimization of engineered hydrogels for organoid.
Hydrogels/chemistry* ; Organoids/cytology* ; Tissue Engineering/methods* ; Humans ; Animals ; Pluripotent Stem Cells/cytology* ; Cell Culture Techniques, Three Dimensional/methods* ; Tissue Scaffolds

Objective:To summarize the clinical characteristics and factors that may affect the flare of patients with systemic lupus erythematosus (SLE).Methods:A total of 300 patients with SLE who were treated with standard treatment in the outpatient clinic of the department of rheumatology and immunology of the Second Affiliated Hospital of Air Force Military Medical University of PLA, were enrolled, and the patients were divided into 24 patients in the complete response group, 40 cases in the no response group, 192 cases in the treatment response group, and 44 cases in the low disease activity group according to the response to treatment. The differences in clinical characteristics and survival rates between the groups were compared and analyzed. Comparisons of count data were made using analysis of variance (ANOVA), comparisons of measurement data were made using the chi-square test or the Fisher′s ecact test, and survival rates were expressed as Kaplan-Meier curves. Cox regression analysis was adapted to explore risk factors for flare in these patients.Results:A total of 300 patients were followed. With a median follow-up time of 18 (1, 36) months, a total of 42 patients experienced flare. The clinical characteristics of the four groups were compared, and there were significant differences in age ( F=4.39, P=0.005), the presence of lupus nephritis ( χ2=12.66, P=0.005), hemoglobin level ( F=2.73, P=0.044), NLR level( F=3.88, P=0.010), cystatin C level( F=3.11, P=0.027), anti-RNP antibody ( χ2=12.04, P=0.007), anti-Sm antibody ( χ2=8.33, P=0.040), anti-SSB antibody ( P=0.014), anti-nucleosome antibody ( P=0.014), and anti-ribosomal P protein antibody ( χ2=11.83, P=0.008). There was no significant difference in survival between the four groups. Cox analysis showed that the combination of other autoimmune diseases [ HR(95%CI)=3.23(1.58, 6.57), P=0.001], anti-Sm antibody [ HR(95%CI)=2.15(1.04, 4.43), P=0.038], and anti-RNP antibody [ HR(95%CI)=2.54(1.13, 5.68), P=0.023] were risk factors for flare in patients with SLE who could reach the treatment target. Conclusion:Patients with SLE with different treatment responses have different clinical features, and all treatment can significantly improve the recurrence rate no matter what level of response to treatment. Patients concurrent with other autoimmune diseases, positive anti-Sm antibodies, and positive anti-RNP antibodies are at highrisk of flare.

Bladder cancer is one of the common malignant tumors of the urinary system,and the results of conventional diagnosis and treatment methods are not satisfactory at this stage.In recent years,photodynamic technology has been applied in the diagnosis and treatment of bladder cancer due to its rapid development,and its effect has been widely recognized in clinical practice.Photodynamic diagnosis(PDD)has shown value in the diagnosis of bladder cancer,and compared with white light cystoscopy(WLC),blue light cystoscopy(BLC)has higher sensitivity and specificity,and is better suitable for the diagnosis of minor lesions and hidden lesions such as CIS,but it is expensive and time-consuming.Non-invasive targeted photodynamic diagnostic techniques using urine as a sample are beginning to show potential;PDD-guided TURBT has better diagnostic sensitivity and surgical precision.Photodynamic therapy(PDT)is an ideal treatment modality for bladder cancer.New photosensitizers have been developed,and two-photon PDT technology,intermittent and rhythmic PDT technology have been applied,which can help to reduce the number of PDT operations and reduce additional trauma while improving the efficacy.Some scholars have tried to use nanotechnology to combine PDT with chemotherapy drugs to further improve the efficacy.Monoclonal antibodies,antibody fragments,protein scaffolds,peptides and small molecule targeted molecular tracers have different characteristics,and new combination therapy methods are being researched and developed,bringing new opportunities for bladder cancer treatment.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective: To explore the relationship between mobile phone dependence (MPD) and academic burden among junior middle school students in Guizhou Province, under the "double reduction" policy by using a multi level model, so as to provide a basis for preventing the occurrence of MPD. Methods: From December 2021 to January 2022, 7 868 students from grade 1 to grade 3 in 3 cities (prefecture) of Guizhou Province were selected by multi stage stratification random sampling method, and on site investigation was conducted by self compiled questionnaire and Self rating Questionnaire for Adolescent Problematic Mobile Phone Use(SQAPMPU). Using MLwiN 2.30 to fit a multi level model of the relationship between MPD and academic burden among junior middle school students. Results: The MPD detection rate of junior middle school students in Guizhou Province was 20.9%. The multi level model revealed that MPD of junior middle school students was clustered at the level of school and class ( χ 2= 1 565.32 , P <0.01), and high perceived academic pressure had a positive predictive effect on MPD among junior middle school students ( β =1.96). Homework duration ≥90 min/d at weekends had a negative predictive effect on MPD ( β =-0.55), while participation in off campus training on learning days had a positive predictive effect ( β =1.66)( P <0.05). Conclusion The MPD occurrence level is higher among junior middle school students in Guizhou Province. Perceived academic pressure, time spent on homework during weekends, off campus training and other academic burdens have an impact on MPD among junior middle school students, which should be a cause of concern for schools, families and social departments.

【Objective】 To evaluate the clinical efficacy and prognostic factors in multiple myeloma (MM) patients treated with autologous hematopoietic stem cell transplantation (auto-HSCT). 【Methods】 The clinical data of 155 MM patients newly diagnosed and suitable for transplantation in our hospital from 2014 to 2021 were retrospectively analyzed. They were divided into auto-HSCT group and non-auto-HSCT group according to the treatment mode. The clinical efficacy, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Furthermore, the prognostic factors of auto-HSCT group were analyzed. 【Results】 ① There were 51 patients in auto-HSCT group and 104 patients in non-auto-HSCT group. There was no statistical difference in baseline characteristics except age between the two groups. ② Hematopoietic reconstruction was achieved in all patients in auto-HSCT group, and no transplantation-related mortality was found. ③ The clinical efficacy of pre-and post-transplantation was compared in auto-HSCT group. sCR/CR rate was significantly increased after transplantation (P=0.041). The effective remission rate (≥VGPR) was also higher (P=0.05). As for the best efficacy, sCR/CR rate and effective remission rate were both significantly higher in auto-HSCT group than in non-auto-HSCT group (P=0.001). ④ In auto-HSCT group, by the end of follow-up, the median OS was not reached, the median PFS was 30.5 months, and 3-year OS and PFS was 87% and 40.3%, respectively. In non-auto-HSCT group, the median OS was 61 months, the median PFS was 21 months, and 3-year OS and PFS was 65.3% and 33.1%, respectively. It indicated that OS was significantly prolonged in auto-HSCT group (P=0.004). PFS was also prolonged but without significant difference (P=0.065). ⑤ Analysis of prognostic factors in auto-HSCT group showed that decreased PLT (P=0.038) and increased serum-adjusted calcium (P=0.017) were independent risk factors for OS, decreased PLT (P=0.005), female (P=0.018) and disease status of PR or worse before transplantation (P=0.012) were independent risk factors for PFS. 【Conclusion】 Auto-HSCT can improve the remission rate, prolong OS in MM patients, and possibly prolong PFS. Increased serum-corrected calcium and decreased PLT are independent prognostic factors for OS in patients treated with auto-HSCT. Decreased PLT, female, and disease status of PR or worse before transplantation are independent prognostic factors for PFS.

Objective To analyze clinical characteristics of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) and to explore the risk factors affecting the occurrence of NPSLE. Methods A total of 63 NPSLE patients and 61 non-NPSLE patients were enrolled. The clinical manifestations and laboratory examination data of the two groups were collected, and the disease characteristics of NPSLE were summarized to analyze the risk factors affecting the occurrence of NPSLE by multivariate Logistic regression. Results The most common clinical manifestations of NPSLE patients were headache (39.7%), affective disorder (33.3%) and cognitive impairment (30.2%), with cranial magnetic resonance abnormalities (63.5%) and a high cerebrospinal fluid protein positive rate (52.4%). Compared with non-NPSLE patients, there were significantly increased levels of Raynaud's phenomenon, renal involvement, anti-RNP antibody, anti-ribosomal P protein, hypocomplementemia, lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) in NPSLE patients. Multivariate Logistic regression analysis showed that renal involvement, Raynaud's phenomenon, positive anti-ribosomal P protein antibody, and elevated LMR and NLR were independent risk factors for NPSLE. Conclusion Headache is the most common symptom in patients with NPSLE, and abnormal cranial MRI and cerebrospinal fluid examination are more common. SLE patients who present with renal involvement, Raynaud's phenomenon, positive anti-ribosomal P protein antibodies, and elevated levels of LMR and NLR are more susceptible to developing NPSLE.
Humans ; Lupus Vasculitis, Central Nervous System ; Risk Factors ; Headache ; Antibodies, Antinuclear ; Cognitive Dysfunction

Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.

Objective: : The present study aimed to identify the function of ischemic stroke (IS) patients’ peripheral blood and its role in IS, explore the pathogenesis, and provide direction for clinical research progress by comprehensive bioinformatics analysis. Methods: : Two datasets, including GSE58294 and GSE22255, were downloaded from Gene Expression Omnibus database. GEO2R was utilized to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the database annotation, visualization and integrated discovery database. The protein-protein interaction (PPI) network of DEGs was constructed by search tool of searching interactive gene and visualized by Cytoscape software, and then the Hub gene was identified by degree analysis. The microRNA (miRNA) and miRNA target genes closely related to the onset of stroke were obtained through the miRNA gene regulatory network. Results: : In total, 36 DEGs, containing 27 up-regulated and nine down-regulated DEGs, were identified. GO functional analysis showed that these DEGs were involved in regulation of apoptotic process, cytoplasm, protein binding and other biological processes. KEGG enrichment analysis showed that these DEGs mediated signaling pathways, including HTLV-I infection and microRNAs in cancer. The results of PPI network and cytohubba showed that there was a relationship between DEGs, and five hub genes related to stroke were obtained : SOCS3, KRAS, PTGS2, EGR1, and DUSP1. Combined with the visualization of DEG-miRNAs, hsa-mir-16-5p, hsa-mir-181a-5p and hsa-mir-124-3p were predicted to be the key miRNAs in stroke, and three miRNAs were related to hub gene. Conclusion : Thirty-six DEGs, five Hub genes, and three miRNA were obtained from bioinformatics analysis of IS microarray data, which might provide potential targets for diagnosis and treatment of IS.