BackgroundNegative symptoms of schizophrenia impose a substantial burden on society， and the current antipsychotic drugs have limited efficacy in treating these symptoms. Intermittent theta burst stimulation （iTBS）， as a novel neuromodulation technique， shows potential therapeutic promise. However， the evidence for its efficacy in treating negative symptoms of schizophrenia and its relationship with associated immuno-inflammatory changes remain to be further elucidated. ObjectiveTo investigate the efficacy of iTBS targeting the left dorsolateral prefrontal cortex （L-DLPFC） on persistent negative symptoms of schizophrenia， and to analyze its relationship with changes in peripheral blood inflammatory markers， so as to provide references for the clinical application of iTBS in treating persistent negative symptoms and to offer clues for further research into its potential biological mechanisms. MethodsA randomized， double-blind， sham-controlled clinical trial was conducted. A total of 60 patients with schizophrenia who were hospitalized at Xuzhou Oriental Peopple's Hospital from February 20， 2024 to May 10， 2025 were consecutively enrolled. All patients met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and fulfilled the criteria for persistent negative symptoms. Participants were randomly assigned into the study group and the control group， with 30 patients in each group. The two groups respectively received 20 sessions of either active iTBS or sham stimulation over a 4-week period. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale （PANSS） at the baseline， the end of treatment， and 3 months after treatment. Peripheral blood inflammatory markers were measured at the baseline and at the end of treatment， including white blood cell count， platelet count， neutrophil count， lymphocyte count， and monocyte count， the neutrophil-to-lymphocyte ratio （NLR）， monocyte-to-lymphocyte ratio （MLR）， and platelet-to-lymphocyte ratio （PLR） were also calculated. A linear mixed model was used to compare PANSS scores between the two groups. Spearman correlation analysis was performed to examine the association between reductions in inflammatory markers at the end of treatment and reductions in PANSS negative symptom subscale scores， with body mass index （BMI） and chlorpromazine-equivalent dose as covariates. Results①The time-group interaction effect for the PANSS negative symptom subscale score was statistically significant （F=5.410， P<0.01）. At the end of treatment and 3 months after treatment， the study group had significantly lower scores on the PANSS negative symptom subscale than the control group （P<0.01）. ② At the end of treatment， group differences in reduction scores for neutrophil count， NLR， and PLR were significant （Z=-2.262， -2.048， -2.070， P<0.05）. However， after FDR correction， the between-group differences in reductions in peripheral blood inflammatory markers were no longer statistically significant （P>0.05）. ③ After adjusting for BMI and chlorpromazine equivalents， the reduction in PANSS negative symptom subscale scores was positively correlated with the reduction in neutrophil count in the study group （r_s=0.382， P=0.045）. ConclusioniTBS targeting the L-DLPFC may be beneficial in improving persistent negative symptoms of schizophrenia， and its clinical efficacy may be associated with changes in neutrophil count. ［Funded by National Natural Science Foundation of China （number， 82371510）； Social Development Project of Jiangsu Province （number， BE2023668）. www.chictr.org.cn number， ChiCTR2500101060］

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To investigate the effect of ambient temperature on body mass, thermogenic activity and un-coupling protein-1 ( UCP1) content of brown adipose tissue ( BAT) in tree shrews ( Tupaia belangeri) , and to provide the-oretical basis for establishing tree shrews model of obesity.Methods Forty healthy adult tree shrews with similar body mass were uesd in our experiment.The tree shrews were divided into five groups (n=8):control group (0 d), the ani-mals were maintained under 25 ±1℃ and 12L:12D ( light : dark, lights on 08:00) photoperiod; and the animals were maintained under 5 ±1℃and 12L:12D photoperiod for 7 d, 14 d, 21 d and 28 d groups, respectively.At the end of ex-periment, the changes of body mass, nonshivering thermogenesis (NST), BAT mass and uncoupling protein 1 (UCP1) con-tent were determined.Results Compared with the control group (0 d), the body mass, NST, BAT mass and UCP1 con-tent of the cold acclimation groups were improved significantly, the BAT color also obviously deepened, and after cold accli-mation for 28 d, the body mass, NST, BAT mass and UCP1 content were increased by 26.32%, 20.65, 53.85%and 43%, respectively.Apparently, the UCP1 content was significantly positively correlated with BAT mass and NST.Conclusions BAT proliferation may be induced and UCP1 expression upregulated by cold acclimation in Tupaia belangeri, therefore, en-hancing the thermogenic activity of brown adipose tissue to increase energy expenditure.We would speculate that BAT might be used as a target organ for treatment of obesity by energetic approach in the future.

OBJECTIVETo construct a personalized full-length fully human antibody mammalian display library for children with systemic lupus erythematosus (SLE).

METHODSThe total RNA was isolated from the PBMCs of SLE children. The heavy chain variable region and kappa light chain (VH and LCκ) of the antibody genes were amplified by RT-PCR and inserted into the pDGB-HC-TM vector separately to construct the heavy chain and light chain libraries. The library DNAs were transfected into 293T cells and the expression of full-length fully human antibody on the surface of 293T cells was analyzed by flow cytometry.

RESULTSUsing 0.8 µg total RNA as the template, the VH and LCκ were amplified and the full-length fully human antibody mammalian display library was constructed. The VH and LCκ gene libraries had a size of 9.4×10(4) and 8.4×10(4), respectively. Sequence analysis of 10 clones randomly selected from the VH and LCκ gene libraries each showed that 8 heavy chain clones and 7 light chain clones contained correct open reading frames, and flow cytometry demonstrated that all the 15 clones express full-length antibodies on 293T cell surfaces. 293T cells co-transfected with the VH and LCκ gene libraries expressed the full-length antibodies on the cell surface.

CONCLUSIONThe personalized full-length fully human antibody library for SLE children constructed allows display of the full-length antibodies on mammalian cell surfaces, thus providing a valuable platform for analyzing the autoantibodies, their etiological role, and their clinical implications in SLE.

Amino Acid Sequence ; Child ; Gene Library ; Genetic Vectors ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin kappa-Chains ; genetics ; Lupus Erythematosus, Systemic ; genetics ; immunology ; Membrane Proteins ; genetics

[Objective ] Intrastriatal Parr interneurons are considered to be the junction between striatal input and output neurons. This study purposes to confirm the morphology of Parr neurons and their distribution in striatum. [Method] Adult male SD rats were perfused and the brains were removed. The sections were conducted with a semiconductor-frozen microtome, then single labeling and double labeling were immunocytochemically conducted with PAP technique. Positive neurons were observed, counted, and calculated, and analyzed with SPSS. [Results] The distribution of Parr positive neurons in striatum was inhomogeueous, and was the most dense in the dorsal lateral area (P<0.001) ; the distribution of Parr positive neurons in matrix compartment was apparently more than patch compartment (82.0% vs 18.0%, P<0.001); Parr positive neurons in striaturn were medium-sized cell bodies with polygonal or oval in shape (mean diameter is 11.68 μm), and were larger in the lateral area than that in the medial area (P<0.01) ; the positive dendrites were dense and smooth without dendrite spines; the positive axons 1 were slender and their collaterals extended in striatum. [Conclusion] The characteristic of Parr positive neurons collecting mostly in lateral striatum and matrix eompartment, as well as their traits of intemeurons, indicated that they would affect the striatal projection neuronal function.