Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). As a key brain region involved in emotional regulation and stress responses, the amygdala has been implicated in the pathogenesis of PMS/PMDD. The amygdala is composed of multiple subregions, each playing distinct roles in emotion, memory, and stress responses, and forms complex brain areas. Summarizing the interconnections among amygdala, subregions and their connectivity with external areas, and exploringt the neuroimaging characteristics of the amygdala, as well as changes in its neural circuits and brain networks in these patients, will help provide a theoretical foundation for targeted modulation of amygdala function in the treatment of PMS/PMDD.
Humans ; Amygdala/diagnostic imaging* ; Female ; Premenstrual Dysphoric Disorder/pathology* ; Premenstrual Syndrome/pathology* ; Emotions/physiology* ; Magnetic Resonance Imaging

METHODS: Cardiac organoids derived from the self-assembled human induced pluripotent stem cells were constructed by regulating the Wnt signaling pathway. Flow cytometry was used to detect the proportion of cardiomyocytes in the cardiac organoids, and RT-qPCR was employed to detect the mRNA expressions. Immunofluorescence staining was used to detect the protein expressions of TNNT2, CD31, and vimentin. The beating amplitude of the cardiac organoids was determined with calcium transient. In vitro myocardial injury models and ischemia-reperfusion models were established, and the cell injuries were examined using Masson staining. TUNEL staining and calcium transient detection were used to evaluate the adverse effects of doxorubicin and trastuzumab in the cardiac organoids. RESULTS: The cardiac organoids began to beat on the 8th day of culture and consisted of 32.4% cardiomyocytes with high expressions of the myocardial markers TNNT2, NKX2.5, RYR2 and KCNJ2. No significant differences in morphological size, beating frequency, proportion of cardiomyocytes, or myocardial contractility were observed in the cardiac organoids differentiated from different batches. These cardiac organoids could be maintained in in vitro culture conditions for at least 50 days. Captopril treatment could obviously alleviate liquid nitrogen-induced myocardial injury in the cardiac organoids. Hypoxia/reoxygenation induced ischemia-reperfusion injury and promoted myocardial fibrosis and apoptosis in the cardiac organoids. Treatment with doxorubicin for 24 h resulted in significantly increased cell death and reduced beating frequency and cell viability in the cardiac organoids in a dose-dependent manner. Trastuzumab significantly impaired the contractile and calcium handling abilities of the cardiac organoids. CONCLUSIONS Cardiac organoids derived from human induced pluripotent stem cells have been successfully constructed and can be used for cardiac disease modeling and drug evaluation.
Humans ; Induced Pluripotent Stem Cells/cytology* ; Organoids/cytology* ; Myocytes, Cardiac/cytology* ; Cell Differentiation ; Heart Diseases

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective To explore the potential regulatory mechanism of resistance exercise in senescence accelerated-prone 8 mice(SAMP8)by evaluating the effects of exercise on the expression of long non-coding RNA(lncRNA)and mRNA in quadriceps muscles by RNA-sequencing(RNA-seq)technology.Methods Twenty-eight-week-old male SAMP8 mice were divided into a model group(M group)and resistance-exercise group(R group)(n=6 mice per group).Another eight normally aging SAMR1 mice of the same age were used as the control group(C group).Mice in R group received 8 weeks of increasing weight climbing exercise training.Relative grip strength was measured every week and the rotarod test was performed every 2 weeks.Histological changes in the right quadriceps femoris were observed by hematoxylin-eosin staining and the left quadriceps was used for RNA-seq.Differentially expressed lncRNA and mRNA were screened and analyzed for enrichment by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses.Finally,key differentially expressed genes were analyzed by quantitative reverse transcription-polymerase chain reaction to verify the accuracy of the RNA-seq result.Results(1)Relative grip strength and rotarod test time were significantly decreased in M group compared with C group(P＜0.01),but were significantly increased after 8 weeks of Rgroup compared with M group(P＜0.01).(2)The cross-sectional area of the muscle fibers was significantly lower in M group compared with C group,as shown by HE staining(P＜0.01),while the cross-sectional area of the muscle fibers was significantly increased in the R group compared with M group(P＜0.01).(3)Differential expression analysis identified 182 upregulated and 218 downregulated lncRNA,and 454 upregulated and 289 downregulated mRNA between M group and R group.The KEGG pathways of lncRNA target genes that were differentially expressed between M group and R group were significantly enriched in intestinal immune network for IgA production,nuclear factor-kappa B signaling pathway,and inflammatory bowel disease.Conclusions(1)This study demonstrated that resistance exercise can improve skeletal muscle function in SAMP8 mice with sarcopenia.We identified lncRNA and mRNA that were differentially expressed as a result of resistance exercise,and which might be potential targets of sarcopenia therapy.(2)Furthermore,analyzing the biological functions of the target genes of the differentially expressed lncRNA and mRNA may further our understanding of the mechanism of resistance exercise for improving sarcopenia.

Objective:To investigate the factors influencing phytohemagglutinin (PHA) response in the detection of Mycobacterium tuberculosis infection by gamma interferon release assay (IGRA). Methods:A retrospective case-control study was conducted on 360 hospitalized patients who received IGRA in West China Hospital of Sichuan University from January 2019 to December 2021. According to PHA response (IFN-γ level), they were divided into three groups: negative mitogen response group (IFN-γ<2 pg/ml), weak positive mitogen response group (IFN-γ: 2-100 pg/ml), and normal mitogen response group (IFN-γ>400 pg/ml).Results:Immune diseases were independently associated with negative (OR=0.34, 95%CI: 0.17-0.72, P=0.004) and weak positive mitogen responses (OR=0.29, 95%CI: 0.16-0.55, P<0.001). Infections caused by pathogens other than Mycobacterium tuberculosis was independently associated with negative mitogen response (OR=0.266, 95%CI: 0.09-0.83, P=0.023), while immunodeficiency was independently associated with weak positive mitogen response (OR=0.280, 95%CI: 0.12-0.63, P=0.002). Mitogen response was significantly correlated with the levels of albumin and hemoglobin in serum and the counts of neutrophils and lymphocytes ( P<0.001). Conclusions:Immune diseases and immunodeficiency can affect mitogen response. Therefore, clinicians should give attention to mitogen response in the interpretation of IGRA test results to prevent misdiagnosis and underdiagnosis. Besides, to a certain extent, mitogen response can reflect the infection status of hospitalized patients.

Objective:To analyze the epidemiological characteristics of respiratory virus infections in Sichuan from 2017 to 2023, and investigate the changes in detection rates of various viruses in different periods and age groups.Methods:The study included 41 516 patients with acute respiratory infections. Clinical laboratory results of these patients were retrospectively collected to calculate the detection rates of various viruses. The epidemiological characteristics of respiratory virus infections before, during, and after the COVID-19 pandemic, the prevalence of mixed infections, and the detection rates in different seasons and age groups were analyzed.Results:The overall detection rate of respiratory viruses was 23.35% (9 696/41 516), with influenza A virus (8.47%, 3 515/41 516), rhinovirus (7.13%, 2 961/41 516), and influenza B virus (2.04%, 846/41 516) being the most prevalent. The highest detection rate was observed in children aged 0-14 years (48.62%, 1 429/2 939), while the detection rates in young, middle-aged, and elderly individuals were similar [21.00% (1 482/7 057), 22.06% (3 828/17 350), 20.33% (2 685/13 205)]. The detection rate of influenza A virus dropped to 1.35% (253/18 717) during the COVID-19 pandemic, and rebounded to 13.05% (1 560/11 953) after the pandemic. A similar pattern was observed in other viruses such as human metapneumovirus, influenza B virus, coronavirus, and respiratory syncytial virus, with significant reductions during the COVID-19 pandemic and subsequent increases that even exceeded pre-pandemic levels. The detection rates of adenovirus, bocavirus, and rhinovirus gradually decreased over time, while the prevalence of parainfluenza virus remained stable, indicating a less significant impact of COVID-19 on these viruses. Higher detection rates were observed in autumn (28.90%, 2 324/8 041) and winter (26.52%, 4 093/15 433) as compared to that in spring (17.61%, 1 848/10 494) and summer (18.96%, 1 431/7 548), suggesting significant seasonal impacts on virus detection rates ( P<0.001). This study identified 8 666 cases of single-virus infections, 948 double infections, 77 triple infections, and five quadruple infections. Co-infection of bocavirus and rhinovirus was the most common type of double infections (17.41%, 165/948), and 59.60% (565/948) of double infections involved rhinovirus. Conclusions:The overall detection rate of respiratory viruses is higher in autumn and winter than in spring and summer. The prevalence of some respiratory viruses such as influenza viruses decreases during the COVID-19 pandemic. People of different ages can develop multiple infections with rhinovirus being the most common in double infections.

OBJECTIVE: To assess the value of Ploton silver staining and phalloidin-iFlour 488 staining in observation of the morphology of osteocyte dendrites of mice at different developmental stages. METHODS: The humerus and femurs were harvested from mice at 0 (P0), 5 (P5), 15 (P15), 21 (P21), 28 (P28), and 35 days (P35) after birth to prepare cryo-sections and paraffin sections. HE staining of P35 mouse femur sections served as a reference for observing osteocytes in the trabecular bone and cortical bone. The humeral sections at different developmental stages were stained with Ploton silver staining to observe the morphology of osteocytes and canaliculi, and the canalicular lengths in the cortical and trabecular bones of the humerus of the mice in each developmental stage were recorded. The cryo-sections of the humerus from P10 and P15 mice were stained with phalloidin iFlour-488 to observe the morphology of osteocytes and measurement of the length of osteocyte dendrites in the cortical bone. RESULTS: In the trabecular bone of the humerus of P0-P15 mice, Ploton silver staining only visualized the outline of the osteocytes, and the morphology of the canaliculi was poorly defined. In P21 or older mice, Ploton silver staining revealed the morphology of the trabecular bone osteocytes and the canaliculi, which were neatly arranged and whose lengths increased significantly with age (P21 CONCLUSIONS Mouse osteocyte dendrites elongate progressively and their arrangement gradually becomes regular with age. Ploton silver staining can clearly visualize the morphology of the osteocytes and the canaliculi in adult mice but not in mice in early stages of development. Phalloidin iFlour-488 staining for labeling the cytoskeleton can be applied for mouse osteocytes at all developmental stages and allows morphological observation of mouse osteocytes in early developmental stages.
Animals ; Bone and Bones ; Dendrites ; Mice ; Osteocytes ; Phalloidine ; Silver Staining

Objective: To explore the visuospatial memory characteristics of school-age children with exotropia and to analyze associated factors. Methods: Based on a case-control study,45 exotropia children aged 8-12 years and 45 normal control children were recruited from 2017-2019. The "tapping test" was used to evaluate the visuospatial short-term and working memory of children. Results: There was no significant differences in the scores of visuospatial short-term memory between the exotropia group and the control group [(7.64±1.69)(8.00±1.66)，t=-1.00，P=0.32)]. The scores of visuospatial working memory in the control group were higher than those in the exotropia group [(5.98±1.23)(6.80±1.53)，t=-2.81，P=0.01)]. In the reverse tapping test,the better the near stereopsis was,the higher the score was (B=0.78,95%CI=0.23-1.33,P=0.01),and the constant exotropia children performed better than the intermittent exotropia children(B=1.25,95%CI=0.16-2.24,P=0.03). Conclusion Visuospatial working memory is impaired in school-age children with exotropia,and the visuospatial working memory of exotropia children is affected by the near stereopsis and exotropia constancy.