Journal of Zhejiang University SCIENCE B最新文献

Objectives: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.

Methods: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.

Results: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania.

Conclusions: This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.

Copper sulfate is a frequently used copper compound in laboratory settings, with instances of poisoning being uncommon. A study conducted by the American Association of Poison Control Centers' National Poison Data System found that only 140 individuals were exposed to copper compounds over the course of a year, with five cases being intentional (Gummin et al., 2023). Severe poisoning from copper sulfate can result in isolated gastrointestinal injury (Galust et al., 2023), intravascular hemolysis (Adline et al., 2024), rhabdomyolysis (Richards et al., 2020), and other symptoms documented in the literature. However, there have been no reports of long-term uncontrolled hyperglycemia in patients with copper sulfate poisoning. This case study documents the treatment approach for a patient with unexplained, long-term, uncontrolled hyperglycemia, alongside multiple organ dysfunction resulting from intentional ingestion of a large dose of copper sulfate. This case report details the long-term complications in a patient's recovery from acute copper sulfate, highlighting the significance of ongoing monitoring and intervention.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, belonging to the type II CRISPR/Cas system, is an effective gene-editing tool widely used in different organisms, but the size of Streptococcus pyogenes Cas9 (SpCas9) is quite large (4.3 kb), which is not convenient for vector delivery. In this study, we used a codon-optimized Staphylococcus aureus Cas9 (SaCas9) system to edit the tyrosinase (tyr), oculocutaneous albinism II (oca2), and paired box 6.1 (pax6.1) genes in the fish model medaka(Oryzias latipes), in which the size of SaCas9 (3.3 kb) is much smaller and the necessary protospacer-adjacent motif (PAM) sequence is 5'-NNGRRT-3'. We also used a transfer RNA (tRNA)‍-single-guide RNA (sgRNA) system to express the functional sgRNA by transcription eitherin vivo or in vitro, and the combination of SaCas9 and tRNA-sgRNA was used to edit the tyr gene in the medaka genome. The SaCas9/sgRNA and SaCas9/tRNA-sgRNA systems were shown to edit the medaka genome effectively, while the PAM sequence is an essential part for the efficiency of editing. Besides, tRNA can improve the flexibility of the system by enabling the sgRNA to be controlled by a common promoter such as cytomegalovirus. Moreover, the all-in-one cassette cytomegalovirus (CMV)‍-SaCas9-tRNA-sgRNA-tRNA is functional in medaka gene editing. Taken together, the codon-optimized SaCas9 system provides an alternative and smaller tool to edit the medaka genome and potentially other fish genomes.

Multilayer paper-based cell culture, as an in vitro three-dimensional (3D) cell culture method, has been frequently used to research drug bioavailability, therapeutic efficacy, and dose-limiting toxicity in malignant tumors. This paper proposes a heterogenous multilayer paper stacking co-culture system to establish a model of natural killer (NK) cells moving through the endothelium layer and attacking tumor spheroids. This system consists of three layers: a bottom tumor-spheroid layer, a middle invasion layer, and a top endothelium layer. NK-92 cells were placed in the supernatant on top of the three layers. After two days of co-culture, the attack of tumor spheroids by NK cells was observed. We additionally examined the infiltration of NK-92 cells within the tumor spheroids at different Z-axis depths using a confocal microscope, and the results suggested that the system successfully realizes NK cells traveling cross the endothelium layer to form tumor-infiltrating NK cells (TINKs). The potential application of multilayer paper for co-culture models involving cancer cells and immune cells holds great promise for exploring the interaction dynamics of these two cell types.

In light of the lack of reliable molecular markers for odontogenic myxoma (OM), the detection of copy number variation (CNV) may present a more objective method for assessing ambiguous cases. In this study, we employed multiregional microdissection sequencing to integrate morphological features with genomic profiling. This allowed us to reveal the CNV profiles of OM and compare them with dental papilla (DP), dental follicle (DF), and odontogenic fibroma (OF) tissues. We identified a distinct and robustly consistent CNV pattern in 93.75% (30/32) of OM cases, characterized by CNV gain events in chromosomes 4, 5, 8, 10, 12, 16, 17, 20, and 21. This pattern significantly differed from the CNV patterns observed in DP, DF, and OF. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated potential links between this CNV patterns and the calcium signaling pathway and salivary secretion, while Gene Ontology (GO) term analysis implicated CNV patterns in tumor adhesion, tooth development, and cell proliferation. Comprehensive CNV analysis accurately identified a case that was initially disputable between OF and OM as OM. Our findings provide a reliable diagnostic clue and fresh insights into the molecular biological mechanism underlying OM.

White-matter tracts play a pivotal role in transmitting sensory and motor information, facilitating interhemispheric communication and integrating different brain regions. Meanwhile, sensorimotor disturbance is a common symptom in patients with major depressive disorder (MDD). However, the role of aberrant sensorimotor white-matter system in MDD remains largely unknown. Herein, we investigated the topological structure alterations of white-matter morphological brain networks in 233 MDD patients versus 257 matched healthy controls (HCs) from the DIRECT consortium. White-matter networks were derived from magnetic resonance imaging (MRI) data by combining voxel-based morphometry (VBM) and three-dimensional discrete wavelet transform (3D-DWT) approaches. Support vector machine (SVM) analysis was performed to discriminate MDD patients from HCs. The results indicated that the network topological changes in node degree, node efficiency, and node betweenness were mainly located in the sensorimotor superficial white-matter system in MDD. Using network nodal topological properties as classification features, the SVM model could effectively distinguish MDD patients from HCs. These findings provide new evidence to highlight the importance of the sensorimotor system in brain mechanisms underlying MDD from a new perspective of white-matter morphological network.

White-matter tracts play a pivotal role in transmitting sensory and motor information, facilitating interhemispheric communication and integrating different brain regions. Meanwhile, sensorimotor disturbance is a common symptom in patients with major depressive disorder (MDD). However, the role of aberrant sensorimotor white-matter system in MDD remains largely unknown. Herein, we investigated the topological structure alterations of white-matter morphological brain networks in 233 MDD patients versus 257 matched healthy controls (HCs) from the DIRECT consortium. White-matter networks were derived from magnetic resonance imaging (MRI) data by combining voxel-based morphometry (VBM) and three-dimensional discrete wavelet transform (3D-DWT) approaches. Support vector machine (SVM) analysis was performed to discriminate MDD patients from HCs. The results indicated that the network topological changes in node degree, node efficiency, and node betweenness were mainly located in the sensorimotor superficial white-matter system in MDD. Using network nodal topological properties as classification features, the SVM model could effectively distinguish MDD patients from HCs. These findings provide new evidence to highlight the importance of the sensorimotor system in brain mechanisms underlying MDD from a new perspective of white-matter morphological network.

This systematic review and meta-analysis considered the results of randomized controlled clinical trials (RCTs) to evaluate the efficacy of systemic or local antibiotic therapy in peri-implantitis. Two independent authors screened publications from three electronic databases to include RCTs meeting all the inclusion and exclusion criteria. A meta-analysis was performed to evaluate the weighted mean differences in survival rate (SR) and changes in pocket probing depth (PPD), bone level (BL), and clinical attachment level (CAL). The study cohorts were defined as antibiotic and control groups with subgroups for analysis. Seven studies including 309 patients (390 implants) were considered. Within the limitations of this review, patients in the antibiotic groups exhibited significant improvements in PPD. Subgroup analysis indicated that the administration of systemic antibiotics or the use of antibiotics in non-surgical treatments did not result in a significant alteration in BL. It was established that the addition of antibiotics can ameliorate PPD and SR in the treatment of peri-implantitis, whether through surgical or non-surgical approaches, and also shows moderate performance regarding BL and CAL. Considering the lack of application of new technologies in the control group and the hardship of assessing the potential risks of antibiotics, careful clinical judgment is still necessary.

The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.

Atypical sensory responsivity is widely reported in autistic individuals and is related to elevated functional difficulties. Dynamically, altered initial responses and/or habituation rates could underlie their atypical averaged responses to repeated sensory stimuli. In this study we aimed to measure the arousal level in response to different types of auditory stimuli and the dynamic change of atypical arousal level using pupillometry in autistic children. In Experiment 1, 43 autistic children and 49 neurotypical (NT) children were asked to passively listen to a mild sound and an aversive sound repeatedly. In Experiment 2, 39 autistic children and 44 NT children who went through Experiment 1 listened to a gradually emerging non-startling sound and a suddenly emerging startling sound in a random order. We found that the autistic group showed hyper-arousal in response to the aversive sound and the startling sound as reflected by their larger change in pupil area. In comparison, these autistic children demonstrated normal arousal in response to the mild sound and the non-startling sound. Dynamically, the autistic group had a larger peak pupil area change than the NT group in the first trial and a normal habituation rate to the aversive sound. In summary, our results suggest hyper-arousal to aversive and startling stimuli and the role of larger initial responses in hyper-arousal in autism. Minimizing aversive and startling sensory stimuli or gradually increasing the volume of aversive auditory stimuli to allow autistic children to adapt using the principle of habituation is recommended to reduce the arousal level and problematic behaviors of autistic children.