Co-occurrence of Erdheim-Chester disease and clonally evolving acute myeloid leukemia with FLT3-ITD and PTPN11 mutations.

Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring.

Dynamic regulation of phosphorylation of NMDA receptor GluN2B subunit tyrosine residues mediates ketamine rapid antidepressant effects.

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyr1472NR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses. The dynamic regulation of phosphorylation of NR2B provides a new perspective for developing new antidepressant strategies.

Trends in confinement-induced cell migration and multi-omics analysis.

Cell migration is an essential manner of different cell lines that are involved in embryological development, immune responses, tumorigenesis, and metastasis in vivo. Physical confinement derived from crowded tissue microenvironments has pivotal effects on migratory behaviors. Distinct migration modes under a heterogeneous extracellular matrix (ECM) have been extensively studied, uncovering potential molecular mechanisms involving a series of biological processes. Significantly, multi-omics strategies have been launched to provide multi-angle views of complex biological phenomena, facilitating comprehensive insights into molecular regulatory networks during cell migration. In this review, we describe biomimetic devices developed to explore the migratory behaviors of cells induced by different types of confined microenvironments in vitro. We also discuss the results of multi-omics analysis of intrinsic molecular alterations and critical pathway dysregulations of cell migration under heterogeneous microenvironments, highlighting the significance of physical confinement-triggered intracellular signal transduction in order to regulate cellular behaviors. Finally, we discuss both the challenges and promise of mechanistic analysis in confinement-induced cell migration, promoting the development of early diagnosis and precision therapeutics.

Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration.

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, the mechanism underlying this type of cell migration remains unclear. Here we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo epithelial-mesenchymal transition-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-hijacked RhoA signaling significantly alters cellular morphology and rearranges the actin cytoskeleton involving the depolymerization of robust actin stress fibers, leading-edge protrusion formation, and the rear-edge recontraction, which coordinates VACV-induced cell migration. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.

Periodontitis aggravates renal inflammatory response in a mouse model of renal fibrosis.

OBJECTIVES: To assess the effects of periodontitis on renal interstitial fibrosis in a mouse model. MATERIALS AND METHODS: Thirty C57BL/6 male mice were divided into control, periodontitis (PD), unilateral ureteral ligation (UUO) and PD+UUO groups. Unilateral ureteral ligation was performed 6 days after periodontitis. After 2 weeks, all mice were sacrificed, and samples were collected for the assessment of gene expression, immune cells, biochemical indicators and renal pathology. RESULTS: Expression of tumour necrosis factor-α, interleukin-1ß, and Ly6G in the kidneys in the PD+UUO group was significantly greater than in the UUO group. The percentage of CD11b+ Ly6G+ cells was significantly higher in the PD+UUO than in the UUO group. Fibrotic areas in the kidneys in the PD+UUO group were slightly, but not significantly, greater than those in the UUO group. Kidneys from the PD+UUO group showed markedly higher gene expression of matrix metalloproteinase-9, but not α-smooth muscle actin or collagen I, than those in the UUO group. There were no significant differences in blood urea nitrogen, serum creatinine and uric acid between the PD+UUO and UUO groups. CONCLUSIONS: Periodontitis increases the renal inflammatory response without showing a significant influence on renal interstitial fibrosis or renal function in the UUO mouse model.

KCTD11 inhibits progression of lung cancer by binding to ß-catenin to regulate the activity of the Wnt and Hippo pathways.

KCTD11 has been reported to be a potential tumour suppressor in several tumour types. However, the expression of KCTD11 and its role has not been reported in human non-small cell lung cancer (NSCLC). Whether its potential molecular mechanism is related to its BTB domain is also unknown. The expression of KCTD11 in 139 NSCLC tissue samples was detected by immunohistochemistry, and its correlation with clinicopathological factors was analysed. The effect of KCTD11 on the biological behaviour of lung cancer cells was verified in vitro and in vivo. Its effect on the epithelial-mesenchymal transition(EMT)process and the Wnt/ß-catenin and Hippo/YAP pathways were observed by Western blot, dual-luciferase assay, RT-qPCR, immunofluorescence and immunoprecipitation. KCTD11 is under-expressed in lung cancer tissues and cells and was negatively correlated with the degree of differentiation, tumour-node-metastasis (TNM) stage and lymph node metastasis. Low KCTD11 expression was associated with poor prognosis. KCTD11 overexpression inhibited the proliferation and migration of lung cancer cells. Further studies indicated that KCTD11 inhibited the Wnt pathway, activated the Hippo pathway and inhibited EMT processes by inhibiting the nuclear translocation of ß-catenin and YAP. KCTD11 lost its stimulatory effect on the Hippo pathway after knock down of ß-catenin. These findings confirm that KCTD11 inhibits ß-catenin and YAP nuclear translocation as well as the malignant phenotype of lung cancer cells by interacting with ß-catenin. This provides an important experimental basis for the interaction between KCTD11, ß-catenin and YAP, further revealing the link between the Wnt and Hippo pathways.

[Correlation analysis of color change and Maillard reaction during processing of Gardeniae Fructus Praeparatus].

The chromaticity space parameters of the samples during the processing of Gardeniae Fructus Praeparatus(Jiaozhizi in Chinese herbal name, JZZ) were measured by the visual analyzer to analyze the color variation rule during the processing of JZZ, and the content changes of total reducing sugar, total amino acid and 5-hydroxymethylfurfural(5-HMF) related to Maillard reaction were measured. Pearson correlation analysis and linear regression analysis of the data were carried out by SPSS 24.0 software. The experimental results showed that the objective coloration of the samples in the processing of JZZ was basically consistent with the traditional subjective color judgment; the contents of total reducing sugar and total amino acids showed a decreasing trend during the processing of JZZ, and the content of 5-HMF showed an increasing trend, which was in line with Maillard reaction law. Pearson correlation analysis results showed that there was a significant correlation between the chromaticity space parameters L~*(lightness value), a~*(red green value), b~*(yellow blue value), E~*ab(total color value) and the contents of total reducing sugar, total amino acid and 5-HMF(P<0.01), among which the values of L~*, a~*, b~*, E~*ab were positively correlated with the contents of total reducing sugar and total amino acid, and negatively correlated with the contents of 5-HMF. The results of linear regression analysis also showed that these two were highly correlated. In this study, by establishing the correspondence relationship between the color change of JZZ processing and Maillard reactants, wecan not only provide a basis for the objective digital expression of subjective color of JZZ, but also provide a reference for explaining the processing mechanism of JZZ from a new perspective.

Interaction of basolateral amygdala, ventral hippocampus and medial prefrontal cortex regulates the consolidation and extinction of social fear.

BACKGROUND: Following a social defeat, the balanced establishment and extinction of aversive information is a beneficial strategy for individual survival. Abnormal establishment or extinction is implicated in the development of mental disorders. This study investigated the time course of the establishment and extinction of aversive information from acute social defeat and the temporal responsiveness of the basolateral amygdala (BLA), ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) in this process. METHODS: Mouse models of acute social defeat were established by using the resident-intruder paradigm. To evaluate the engram of social defeat, the intruder mice were placed into the novel context at designated time to test the social behavior. Furthermore, responses of BLA, vHIP and mPFC were investigated by analyzing the expression of immediate early genes, such as zif268, arc, and c-fos. RESULTS: The results showed after an aggressive attack, aversive memory was maintained for approximately 7 days before gradually diminishing. The establishment and maintenance of aversive stimulation were consistently accompanied by BLA activity. By contrast, vHIP and mPFC response was inhibited from this process. Additionally, injecting muscimol (Mus), a GABA receptor agonist, into the BLA alleviated the freezing behavior and social fear and avoidance. Simultaneously, Mus treatment decreased the zif268 and arc expression in BLA, but it increased their expression in vHIP. CONCLUSION: Our data support and extend earlier findings that implicate BLA, vHIP and mPFC in social defeat. The time courses of the establishment and extinction of social defeat are particularly consistent with the contrasting BLA and vHIP responses involved in this process.

Molecular characterization and function analysis of grouper (Epinephelus coioides) Bruton's tyrosine kinase BTK.

Bruton's tyrosine kinase (BTK) is a Tec-family tyrosine kinase and plays a crucial role in B cell antigen receptor (BCR) signal pathway. Mutations in humans and mice BTK gene results in X-linked agammaglobulinemia (XLA) and X-linked immunodeficiency (XLD), respectively. To study the function of BTK in teleost, we cloned a BTK gene from orange-spotted grouper. Homology analysis showed that the grouper BTK (EcBTK) had a high amino acid identity with other vertebrates (63%-92%) and shared the highest amino acid identity with ballan wrasse Labrus bergylta BTK. EcBTK comprises a Bruton's tyrosine kinase pleckstrin homology (PH) domain, a Tec homology (TH) domain, a Src homology 3 (SH3) domain, a Src homology 2 (SH2) domain and a Protein Kinases, catalytic (PKc) domain. Tissue distribution analysis showed that EcBTK was mainly expressed in immune organs. EcBTK was uniform distributed throughout the cytoplasm of transfected HEK293T cells and overexpression of EcBTK slightly down-regulates NF-κB activity. Ibrutinib treatment can reduce the phosphorylation level of grouper's BTK. In groupers infected with Cryptocaryon irritans, up-regulation of EcBTK were not seen in the early stage of infected skin and gill until days 14-21. The phosphorylation level of grouper BTK was significantly increased in infected skin and gill.

Rhodobacter sphaeroides Extract Lycogen™ Attenuates Testosterone-Induced Benign Prostate Hyperplasia in Rats.

Benign prostate hyperplasia (BPH) is one of the most common urological problems in mid-aged to elderly men. Risk factors of BPH include family history, obesity, type 2 diabetes, and high oxidative stress. The main medication classes for BPH management are alpha blockers and 5α-reductase inhibitors. However, these conventional medicines cause adverse effects. Lycogen™, extracted from Rhodobacter sphaeroides WL-APD911, is an anti-oxidant and anti-inflammatory compound. In this study, the effect of Lycogen™ was evaluated in rats with testosterone-induced benign prostate hyperplasia (BPH). Testosterone injections and Lycogen™ administration were carried out for 28 days, and body weights were recorded twice per week. The testosterone injection successfully induced a prostate enlargement. BPH-induced rats treated with different doses of Lycogen™ exhibited a significantly decreased prostate index (PI). Moreover, the Lycogen™ administration recovered the histological abnormalities observed in the prostate of BPH rats. In conclusion, these findings support a dose-dependent preventing effect of Lycogen™ on testosterone-induced BPH in rats and suggest that Lycogen™ may be favorable to the prevention and management of benign prostate hyperplasia.

The effect of biochar and crop straws on heavy metal bioavailability and plant accumulation in a Cd and Pb polluted soil.

Biochar derived from various materials has been investigated with regard to its ability to decrease the bioavailability of heavy metals in contaminated soils, and thus reduce their potential to enter the food chain. However, little attention has been given to the adsorption capacity of untreated crop straws, which are commonly used as a biochar feedstock, especially in soils. Hence, this study was conducted to investigate the effect of crop straws on heavy metal immobilization and subsequent heavy metal uptake by maize and ryegrass in a soil artificially polluted by Cd and Pb. Bamboo biochar, rice straw, and wheat straw were mixed into soil four weeks before the experiment, enabling them to reach equilibrium at 2% (w/w), 1% (w/w), and 1% (w/w), respectively. The results showed that soil pH for both species was significantly increased by all treatments, except when wheat straw was used for ryegrass cultivation. Soil organic carbon was only improved in the rice straw treatment and the soil alkali-hydrolyzable N content was significantly decreased with all of the amendments, which may have contributed to the lack of an effect on plant biomass. Soil available Cd was significantly lower in the rice straw treatment than in the control soil, while Pb levels clearly decreased in wheat straw treatment. The Cd concentration in shoots of maize was reduced by 50.9%, 69.5%, and 66.9% with biochar, rice straw, and wheat straw, respectively. In addition, shoot Cd accumulation was decreased by 47.3%, 67.1%, and 66.4%, respectively. Shoot Pb concentration and accumulation were only reduced with the rice straw treatment for both species. However, metal uptake in plant roots was more complex, with increased metal concentrations also detected. Overall, the direct application of crop straw could be considered a feasible way to immobilize selected metals in soil, once the long-term effects are confirmed.

[Acupuncture Regulated the Expressions of Hsp84 and Hsp86 and Postponed Brain Aging in SAMP8].

Objective To observe the correlations between heat shock protein 84 ( Hsp84)/ Hsp86 and brain aging in senescence accelerated mouse prone 8 (SAMP8) and the regulation effects of acupuncture. Methods Ten senescence accelerated mouse resistant 1 (SAMR1) were recruited as a normal control group. Another 30 SAMP8 mice were divided into the blank control group, the acupuncture group, and the non-acupoint group by random digit table, 10 in each group. Mice in the acupuncture group received treatment with "Sanjiao" acupuncture method. Mice in the non-acupoint group were needled at two fixed non-acupoints located at bilateral hypochondrium of the body. Catching stimulus at equal volume was given to mice in the rest two groups. All intervention was performed once per day for 15 successive days. Neuromuscular coordination of mice was evaluated. Levels of oxidative stress and protein carbonyl were determined. mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus of mice and Neuro-2a cells were detected using Real-time PCR and Western blot. Results Compared with the normal control group, the success rate of tight rope experiment was lowered (P <0. 01) , levels of super- oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were reduced (P < 0. 01) , the levels of superoxide anion and protein carbonyl increased (P <0. 01, P <0. 05), mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus decreased (P <0. 01) in the blank con- trol group. Compared with the blank control group and the non-acupoint group, the success rate of tight rope experiment was elevated (P <0. 05) , levels of SOD and GSH-Px were increased (P <0. 05, P < 0. 01) , the levels of superoxide anion and protein carbonyl decreased (P <0. 01 , P <0. 05), and expres- sion levels of Hsp84 and Hsp86 in the hippocampus increased (P <0. 01) in the acupuncture group. mR- NA expression levels of Hsp84 and Hsp86 were decreased in Neuro-2a cells after treated with AP21-35 (P <0. 01). Conclusions Increased oxidative damage of protein and decreased expression levels of Hsp84 and Hsp86 might be partial reasons for resulting in accumulation of denatured protein and brain aging in SAMP8. Acupuncture could delay brain aging by regulating the expressions of Hsp84 and Hsp86.

[Analysis of volatile ingredients in Gardeniae Fructus and its processed products by GC-MS].

Gardeniae Fructus contains volatile ingredients, however, the species and proportions in different processed products of Gardeniae Fructus are different. In this experiment, volatile ingredients were separated by steam distillation with content of 1.2, 1.0, 0.9, 0.7 µL · g(-1) in Gardeniae Fructus, fried Gardeniae Fructus, stir-baked Gardeniae Fructus, Gardeniae Fructus fried into carbon respectively. One hundred and twenty-four kinds of volatile components were identified by GC-MS. Fifty-three kinds of volatile ingredients consisted in Gardeniae Fructus accounting for 93.85%, 54 kinds in fried Cardeniae Fructus accounting for 92.01%, 32 kinds in stir-baked Cardeniae Fructus accounting for 91.59% and 43 kinds in Gardeniae Fructus fried into carbon accounting for 90.81%. In this paper, analysis of Gardeniae Fructus by GC-MS provides a scientific basis for elucidating the mechanism of different processed products.

The effects of venlafaxine on cortical motor area activity in healthy subjects: a pilot study.

In the study, we used functional magnetic resonance imaging associated with behavioral assessment to observe the effects of venlafaxine on the modulation of human motor cortex activation and to provide preliminary data for further assessing its influence on motor functional reorganization after stroke injury. In a randomized, double-blind, crossover study, 8 right-handed subjects received 75 mg of either venlafaxine or a placebo daily over a period of 7 days separated by 3 washout days. The volunteers were asked to execute motor tasks, which included the dynamometer and finger-tapping test. In addition, laboratory tests and functional magnetic resonance imaging examination, before the start of the experiment and after administration of placebo and venlafaxine, were performed. It was shown that the finger-tapping rate of each hand in the venlafaxine stage was significantly improved compared with that observed in the placebo stage (n = 8, F left hand = 57.69, F right hand = 184.48, P < 0.001). The changes in the recorded grip strengths of both hands were not significant between the stages (n = 8, F = 2.63, P > 0.05). In the venlafaxine stage, the activations of the contralateral primary sensorimotor cortex, contralateral premotor cortex, and contralateral supplementary motor area were enhanced significantly, whereas the activation of the bilateral parietal cortices was decreased when compared with the placebo stage. Meanwhile, the enhancement of contralateral primary sensorimotor cortex activation had a positive correlation with the improvement of the finger-tapping rate. It was concluded that venlafaxine could modulate the cortical excitability and improve finger dexterity and reaction speed, which greatly related to the increase of contralateral motor cortical excitability.

[Effect of acupuncture on transmembrane signal pathway in AD mice: an analysis based on lipid-raft proteomics].

OBJECTIVE: To reveal the transmembrane signal pathway participating in regulating neuron functions of treating Alzheimer's disease (AD) by acupuncture. METHODS: SAMP8 mice was used for AD animal model. The effect of acupuncture method for qi benefiting, blood regulating, health supporting, and root strengthening on the amount and varieties of transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice was detected using HPLC MS/MS proteomics method. RESULTS: Compared with the control group, acupuncture increased 39 transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice, of them, 14 belonged to ionophorous protein, 8 to G protein, 8 to transmembrane signal receptor, and 9 to kinase protein. Totally 3 main cell signal pathways were involved, including G-protein-coupled receptors signal, enzyme linked receptor signal, and ion-channel mediated signal. Compared with the sham-acupuncture group, acupuncture resulted in significant increase of kinase signal protein amount. From the aspect of functions, they were dominant in regulating synapse functions relevant to cytoskeleton and secreting neurotransmitters. CONCLUSION: The cell biological mechanism for treating AD by acupuncture might be achieved by improving synapse functions and promoting the secretion of neurotransmitters through transmembrane signal transduction, thus improving cognitive function of AD patients.

[Research progress on processed Chinese medicine in vivo].

Processed Chinese medicine is the core of traditional Chinese medicine (TCM) industry chain,which directly affects the clinical efficacy and. safety of Chinese patent medicine and clinical formula Decoction pieces. Studied the variation of effective substance in vivo Chinese medicine processing before and after processed, clarifying the effective substance and processing principle is a top priority of the development of Chinese medicine processing. The traditional research method chiefly focus on the variation about chemicals in vitro of processed Chinese medicine, it cannot reveal that the integrity and complexity of processed Chinese medicine efficacy changes, so the change process is the focus of future research in vivo on the base of effective substance of TCM This paper described the research on the base of effective substance of TCM and Processed Chinese medicine research status in vitro, discussed the analytical methods (plasma chemistry, pharmacokinetics, metabonomics) of the dynamic process in vivo about processed Chinese medicine, and pointed out development and related problems in process in vivo on the base of effective substance of TCM, which could provided research ideas and methods for in-depth interpretation of Chinese medicine processing mechanism.

Irrigation and Fertilization Scheduling for Peanut Cultivation under Mulched Drip Irrigation in a Desert-Oasis Area.

The aim of this study was to investigate the impact of water and nitrogen regulation on the characteristics of water and fertilizer demands and the yield, quality, and efficiencies of the water and nitrogen utilization of peanuts cultivated under mulched drip irrigation in a desert-oasis region. The experiment, conducted in Urumqi, Xinjiang, centered on elucidating the response mechanisms governing peanut growth, yield, quality, water consumption patterns, and fertilizer characteristics during the reproductive period under the influence of water and nitrogen regulation. In the field experiments, three irrigation levels were implemented, denoted as W1 (irrigation water quota of 22.5 mm), W2 (irrigation water quota of 30 mm), and W3 (irrigation water quota of 37.5 mm). Additionally, two nitrogen application levels, labeled N1 (nitrogen application rate of 77.5 kg·ha-1) and N2 (a nitrogen application rate of 110 kg·ha-1), were applied, resulting in seven treatments. A control treatment (CK), which involved no nitrogen application, was also included in the experimental design. The results indicate a direct correlation between the increment in the irrigation quota and increases in farmland water-related parameters, including water consumption, daily water consumption intensity, and water consumption percentage. The nitrogen harvest index (NHI) demonstrated a higher value in the absence of nitrogen application compared to the treatment with elevated nitrogen levels. The application of nitrogen resulted in an elevation in both nitrogen accumulation and nitrogen absorption efficiency within pods and plants. When subjected to identical nitrogen application conditions, irrigation proved to be advantageous in enhancing water-use efficiency (WUE), nitrogen partial factor productivity (NPFP), and the yield of peanut pods. The contribution rate of water to pod yield and WUE exceeded that of nitrogen, while the contribution rate of nitrogen to nitrogen-use efficiency (NUE) was higher. The total water consumption for achieving a high yield and enhanced water- and nitrogen-use efficiencies in peanuts cultivated under drip irrigation with film mulching was approximately 402.57 mm. Taking into account yield, quality, and water- and nitrogen-used efficiencies, the use of an irrigation quota of 37.5 mm, an irrigation cycle of 10-15 days, and a nitrogen application rate of 110 kg·ha-1 can be regarded as an appropriate water and nitrogen management approach for peanut cultivation under mulched drip irrigation in Xinjiang.

Enhancing bioretention efficiency for pollutant mitigation in stormwater runoff: Exploring ecosystem cycling dynamics amidst temporal variability.

In this study, three distinct bioretention setups incorporating fillers, plants, and earthworms were established to evaluate the operational efficiency under an ecosystem concept across varying time scales. The results revealed that under short-term operating conditions, extending the drying period led to a notable increase in the removal of NO3--N, total phosphorus (TP), and chemical oxygen demand (COD) by 5 %-7%, 4 %-12 %, and 5 %-10 %, respectively. Conversely, under long-time operating conditions, the introduction of plants resulted in a significant boost in COD removal by 10 %-20 %, while the inclusion of earthworms improved NH4+-N and NO3--N removal, especially TP removal by 9 %-16 %. Microbial community analysis further indicated the favorable impact of the bioretention system on biological nitrogen and phosphorus metabolism, particularly with the incorporation of plants and earthworms. This study provides a reference for the operational performance of bioretention systems on different time scales.

Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis.

Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.

[Effect of acupuncture on the p53 protein expression of mice with Alzheimer's disease].

OBJECTIVE: To observe the effect of acupuncture method for benefiting qi, regulating blood, supplementing the root, and cultivating the essence (BQRBSRCE) on the p53 protein expression of mice with Alzheimer's disease (AD). METHODS: SAMP8 mice were divided into the control group, the acupuncture group, and the non-acupoint group. The homologous SAMR1 control group was set up. Mice in the acupuncture group used acupuncture method for BQRBSRCE by needling at Tanzhong (RN17), Zhongwan (RN12), Qihai (RN6), and bilateral Xuehai (SP10), and bilateral Zusanli (ST36).Two fixed non-acupoints from bilateral ribs were needled in the non-acupoint group. The p53 protein expression in the cortex and hippocampus of mice was determined using Western blot. The pathological changes of neurons in the hippocampal CA1 region, the temporal lobe, and the occipital lobe were observed using HE staining. The expression of cortical p53-positive cells was detected by immunohistochemical assay. RESULTS: The p53 protein was highly expressed in the cortex of SAMP8, which was significantly down-regulated after acupuncture, showing statistical difference when compared with the SAMP8 control group (P < 0.05), but with no statistical difference when compared with the SAMR1 control group (P > 0.05). Needling at non-acupoints had no obvious effect on the p53 protein expression. There was no statistical difference in the p53 protein expression of the hippocampus (P > 0.05). CONCLUSION: Acupuncture method for BQRBSRCE could down-regulate the p53 protein expression in the brain of mice, improve the pathological state of brain cells, thus enhancing learning and memory capabilities of AD mice, improving their cognitive functions, with specificity of acupoints.