Clinical distinctions in symptomatology and psychiatric comorbidities between misdiagnosed bipolar I and bipolar II disorder versus major depressive disorder.

BACKGROUND: To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . METHODS: The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. RESULTS: A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . CONCLUSION: The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.

Arabidopsis PDLP7 modulated plasmodesmata function is related to BG10-dependent glucosidase activity required for callose degradation.

The microdomains of plasmodesmata, specialized cell-wall channels responsible for communications between neighboring cells, are composed of various plasmodesmata-located proteins (PDLPs) and lipids. Here, we found that, among all PDLP or homologous proteins in Arabidopsis thaliana genome, PDLP5 and PDLP7 possessed a C-terminal sphingolipid-binding motif, with the latter being the only member that was significantly upregulated upon turnip mosaic virus and cucumber mosaic virus infections. pdlp7 mutant plants exhibited significantly reduced callose deposition, larger plasmodesmata diameters, and faster viral transmission. These plants exhibited increased glucosidase activity but no change in callose synthase activity. PDLP7 interacted specifically with glucan endo-1,3-ß-glucosidase 10 (BG10). Consistently, higher levels of callose deposition and slower virus transmission in bg10 mutants were observed. The interaction between PDLP7 and BG10 was found to depend on the presence of the Gnk2-homologous 1 (GnK2-1) domain at the N terminus of PDLP7 with Asp-35, Cys-42, Gln-44, and Leu-116 being essential. In vitro supplementation of callose was able to change the conformation of the GnK2-1 domain. Our data suggest that the GnK2-1 domain of PDLP7, in conjunction with callose and BG10, plays a key role in plasmodesmata opening and closure, which is necessary for intercellular movement of various molecules.

BCMA/CD47-directed universal CAR-T cells exhibit excellent antitumor activity in multiple myeloma.

BACKGROUND: BCMA-directed autologous chimeric antigen receptor T (CAR-T) cells have shown excellent clinical efficacy in relapsed or refractory multiple myeloma (RRMM), however, the current preparation process for autologous CAR-T cells is complicated and costly. Moreover, the upregulation of CD47 expression has been observed in multiple myeloma, and anti-CD47 antibodies have shown remarkable results in clinical trials. Therefore, we focus on the development of BCMA/CD47-directed universal CAR-T (UCAR-T) cells to improve these limitations. METHODS: In this study, we employed phage display technology to screen nanobodies against BCMA and CD47 protein, and determined the characterization of nanobodies. Furthermore, we simultaneously disrupted the endogenous TRAC and B2M genes of T cells using CRISPR/Cas9 system to generate TCR and HLA double knock-out T cells, and developed BCMA/CD47-directed UCAR-T cells and detected the antitumor activity in vitro and in vivo. RESULTS: We obtained fourteen and one specific nanobodies against BCMA and CD47 protein from the immunized VHH library, respectively. BCMA/CD47-directed UCAR-T cells exhibited superior CAR expression (89.13-98.03%), and effectively killing primary human MM cells and MM cell lines. BCMA/CD47-directed UCAR-T cells demonstrated excellent antitumor activity against MM and prolonged the survival of tumor-engrafted NCG mice in vivo. CONCLUSIONS: This work demonstrated that BCMA/CD47-directed UCAR-T cells exhibited potent antitumor activity against MM in vitro and in vivo, which provides a potential strategy for the development of a novel "off-the-shelf" cellular immunotherapies for the treatment of multiple myeloma.

Conservative medical intervention as a complement to CDT for BCRL therapy: a systematic review and meta-analysis of randomized controlled trials.

Background: The effect of first-line complex decongestive therapy (CDT) for breast cancer-related lymphedema (BCRL) depending on various factors forces patients to seek additional treatment. Therefore, this meta-analysis was conducted to evaluate the effect of different conservative medical interventions as a complement to CDT. This is the first meta-analysis that includes various kinds of conservative treatments as adjunctive therapy to get broader knowledge and improve practical application value, which can provide recommendations to further improve BCRL patients' health status. Methods: RCTs published before 18 December 2023 from PubMed, Embase, Cochrane Library, and Web of Science databases were searched. RCTs that compared the effects of conservative medical intervention were included. A random-effects or fixed-effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool. Results: Sixteen RCTs with 690 participants were included, comparing laser therapy, intermittent pneumatic compression (IPC), extracorporeal shock wave therapy (ESWT), electrotherapy, ultrasound, diet or diet in combination with synbiotic supplement, traditional Chinese medicine (TCM), continuous passive motion (CPM), and negative pressure massage treatment (NMPT). The results revealed that conservative medical intervention as complement to CDT had benefits in improving lymphedema in volume/circumference of the upper extremity [SMD = -0.30, 95% CI = (-0.45, -0.15), P < 0.05, I 2 = 51%], visual analog score (VAS) for pain [SMD = -3.35, 95% CI (-5.37, -1.33), P < 0.05, I 2 = 96%], quality of life [SMD = 0.44, 95% CI (0.19, 0.69), P < 0.05, I 2 = 0], and DASH/QuickDASH [SMD = -0.42, 95% CI (-0.70, -0.14), P < 0.05, I 2 = 10%] compared with the control group. Subgroup analysis revealed that laser therapy and electrotherapy are especially effective (P < 0.05). Conclusion: Combining conservative medical interventions with CDT appears to have a positive effect on certain BCRL symptoms, especially laser therapy and electrotherapy. It showed a better effect on patients under 60 years old, and laser therapy of low to moderate intensity (5-24 mW, 1.5-2 J/cm2) and of moderate- to long-term duration (≥36-72 sessions) showed better effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354824, identifier CRD42022354824.

Pharmacokinetics and apparent Michaelis constant for metabolite conversion of sorafenib in healthy and hepatocellular carcinoma-bearing rats.

Aim: Investigation of the pharmacokinetics of sorafenib (SRF) in rats with hepatocellular carcinoma (HCC). Methods: A reproducible ultra-HPLC-MS method for simultaneous determination of serum SRF, N-hydroxymethyl sorafenib and N-demethylation sorafenib. Results: Both the maximum serum concentrations (2.5-times) and the area under the serum concentration-time curve from 0 h to infinity (4.5-times) of SRF were observed to be significantly higher, with a greater than 3.0-fold decrease in the clearance rate in the HCC-bearing rats compared with these values in healthy animals. Further study revealed approximately 3.8- and 3.2-times increases in the apparent Michaelis constant for N-hydroxymethyl sorafenib and N-demethylation sorafenib conversions in the HCC-bearing rats. Conclusion: The low efficiency for the SRF conversions was a key contributor to the increased serum concentrations of SRF.

Gender differences in prevalence and associations between cognitive symptoms and suicidal ideation in patients with recurrent major depressive disorder: findings from the Chinese NSSD study.

BACKGROUND: This study aimed to explore gender differences in associations between cognitive symptoms and suicidal ideation (SI) among patients with recurrent major depressive disorder (MDD). METHODS: We recruited 1222 patients with recurrent MDD from the National Survey on Symptomatology of Depression (NSSD), a survey designed to investigate the symptoms experienced during current major depressive episodes in China. A four-point Likert questionnaire was used to assess the frequency of cognitive symptoms and SI in the past two weeks. RESULTS: Gender differences in clinical features and cognitive symptoms of participants with recurrent MDD were found. Specifically, male patients had a higher prevalence of memory loss, decreased verbal output, indecisiveness, and impaired interpersonal relationships, while female patients exhibited a higher prevalence of impaired social and occupational functioning (all P < 0.05). No significant difference in SI prevalence was found between male and female patients. The logistic regression analysis revealed that in male patients, SI was associated with indecisiveness and impaired interpersonal relationships. In female patients, reduced verbal output and impaired social and professional functions were also associated with SI in addition to the above-mentioned variables. CONCLUSION: The findings of gender differences in associations between cognitive symptoms and SI highlight the need to carefully assess gender-specific cognitive predictors of SI in patients with recurrent MDD. This has further implications for more targeted prevention and treatment strategies for SI based on gender.

Program of algorithm for pharmacological treatment of major depressive disorder in China: Benefits or not?

Background: This research was designed to investigate Algorithm Guided Treatment (AGT) and clinical traits for the prediction of antidepressant treatment outcomes in Chinese patients with major depressive disorder (MDD). Methods: This study included 581 patients who had reached treatment response and 406 patients remained non-responded observed after three months of treatment. Sociodemographic factors, clinical traits, and psychiatric rating scales for evaluating therapeutic responses between the two groups were compared. Logistic regression analysis was adopted to determine the risk factors of unresponsive to antidepressant (URA) in MDD. Kaplan-Meier survival analysis was utilized to compare the therapeutic response between AGT and treatment as usual (TAU). Results: Compared to the MDD responsive to antidepressant (RA) group, the URA group had significantly lower rates of the following clinical traits: married status, anxious distress, moderate to severe depressive symptoms, and higher rates of comorbidity (p-value < 0.05). Logistic Regression Analysis showed that eight clinical traits from psychiatric rating scales, such as anxious characteristics, were correlated positively with URA, while the other eight symptoms, such as autonomic symptoms, were negatively correlated. Time to symptomatic remission was longer in TAU without statistically significant (p-value = 0.11) by log-rank testing. Conclusions: The factors may affect the therapeutic responses and compliance of patients, increasing the non-response risk for antidepressants. Therapeutic responses might be improved by increasing the clarification and elucidation of different symptom clusters of patients. Benefits on treatment response to AGT were not found in our study, indicating a one-size-fits-all approach may not work.Trial Registration: We registered as a clinical trial at the International Clinical Trials Registry Platform (No. NCT01764867) and obtained ethical approval 2012-42 from SMHC.

Effect of Artificial Liver Support Systems on Gut Microbiota in Patients with HBV-Related Acute-on-Chronic Liver Failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rare and severe form of end-stage liver disease with high mortality; gut microbes are strongly associated with the development of this severe liver disease but the exact association is unclear. Artificial liver support systems (ALSS) are clinically important in prolonging the waiting time for liver transplantation and in aiding drug therapy to achieve remission. The aim of this study was to investigate the effect of ALSS on the abundance and diversity of microorganisms in the gut of HBV-ACLF patients. In this study, 109 stool samples were collected from patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) for 16S rRNA sequencing. Among them, 44 samples were from patients treated with ALSS therapy as an adjunct to standard medical treatment (SMT) and 65 were from patients receiving SMT only. Analysis of the sequencing results suggested that there were significant differences in the abundance and diversity of gut microbiota between the with-ALSS and without-ALSS groups (p < 0.05). The operational taxonomic units and Shannon indexes indicated that the diversity and abundance of the gut microbiome, while decreasing after the first ALSS treatment, gradually increased after an increase in the number of ALSS therapies. The overall proportion of HBV-ACLF patients with coinfection was 27.59%; the coinfection can reduce the abundance of the Bacteroidetes phylum in the microbiome significantly whereas Proteobacteria were highly enriched. After ALSS therapy, HBV-ACLF patients had a decrease in potentially harmful bacteria, an increase in potentially beneficial bacteria, an increase in the diversity of the intestinal microbiota, and the intestinal microecological disorders were corrected to a certain extent. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels, as well as the international normalized ratio (INR), showed a decreasing trend whereas plasminogen activity (PTA) increased and the condition of patients with HBV-ACLF progressed in a favorable direction. In addition, the abundance of Blautia and Coprococcus was negatively correlated with TBIL and INR, positively correlated with PTA, and positively correlated with disease recovery. Our study shows that ALSS can alter the composition of the gut microbiota and have an ameliorating effect on the gut microecological imbalance in HBV-ACLF patients. It is worth mentioning that Blautia and Coprococcus may have great potential as biomarkers.

Differences in the pharmacokinetics and steady-state blood concentrations of orally administered lenvatinib in adult and juvenile rats.

Objective: The aim of this study was to compare the pharmacokinetics and steady-state serum concentrations of lenvatinib in adult and juvenile rats. Experimental study: An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method was developed to quantify lenvatinib in the serum and liver of rats. Six juvenile and six adult rats in each group were orally administered with a single dose of 7.0 mg/kg lenvatinib suspension for pharmacokinetics. Another 12 juvenile and adult rats were subjected to oral gavage with 7.0 mg/kg lenvatinib once daily for 5 days. Biofluild samples were pre-treated by protein precipitation and sorafenib was used as the internal standard for UPLC-MS analysis. The pharmacokinetic parameters were estimated by compartment and statistical model. The mRNA expression of CYP3A2 and SLC22A1 in liver of adult and juvenile rats was measured by real-time fluorescence quantitative PCR (RT-qPCR). Results: The UPLC-MS method met the requirements for quantitative analysis of lenvatinib in serum and liver. The pharmacokinetic results showed that the mean retention time (MRT(0-∞)) was 19.64 ± 7.64 h and 126.38 ± 130.18 h, with AUC(0-∞) values of 3.97 ± 0.73 µg‧mL-1 h and 5.95 ± 2.27 µg mL-1 h in adult and juvenile rats, respectively. When comparing adult rats (0.35 ± 0.15 µg/mL) to juvenile rats, no significant differences were observed in steady-state serum lenvatinib (0.32 ± 0.11 µg/mL), but a noteworthy decrease to one-third of steady-state liver lenvatinib was observed after multiple oral doses of lenvatinib in juvenile rats. Additional findings revealed that the mRNA expression of CYP3A2 and SLC22A1 was notably increased by 6.86 and 14.67 times, respectively, in juvenile rats compared to adult rats. Conclusion: Juvenile rats exhibit lower levels of lenvatinib in the liver's steady-state, potentially due to the disparity in CYP3A2 mRNA expression. These results imply that the dosage of lenvatinib for pediatric patients may need to be augmented in order to attain the desired clinical outcome.

Screening and Validation Potential Therapeutic Marker of Early to Middle Stage ACLF Patients Treated by ALSSs.

BACKGROUND: Artificial liver support systems (ALSSs) are important approaches for treating acute-on-chronic liver failure (ACLF) patients. Few studies have investigated potential serum therapeutic markers of ACLF patients treated by ALSSs. METHODS: Serum samples were obtained from 57 early to middle stage ACLF patients before and after ALSSs treatment and analyzed by metabonomics. The diagnostic values were evaluated by the area under receiver-operating characteristic curve (AUROC). A retrospective cohort analysis was further employed. RESULTS: Metabonomic study showed that serum ratios of lactate: creatinine in ACLF patients is significantly altered and then restored to normal levels after ALSSs treatment. A retrospective cohort analysis (n = 47) validated that the lactate: creatinine ratio of ACLF patients in the one-month death group remained unchanged after ALSSs treatment, but fell markedly in the survival group with AUROC of 0.682 for diagnosis of survival group from death group, which is a more sensitive measure than measures of prothrombin time activity (PTA) to evaluate the therapeutic effect of ALSSs treatment. CONCLUSIONS: Our results demonstrated the greater the decline in the serum lactate: creatinine ratio with better effective treatments of ALSSs in the ACLF patients with early to middle stage, which presents a potential therapeutic biomarker of ALSSs treatment.

Interleukin-7 as a potential therapeutic target for alleviating hepatic fibrosis in a mice model induced by carbon tetrachloride: implications for fitness and exercise

The effects of interleukin-7 (IL-7) on the carbon tetrachloride (CCL4) induced hepatic fibrosis were investigated in this study. Thirty-six female BALB/C mice were randomized into group A (control group) injected with saline, group B (fibrotic model group) and group C (IL-7 intervention group). Histopathological changes were observed by HE, Masson as well as reticular fiber staining. The apoptosis cells and hepatic stellate cell (HSC) were detected from the tissues, and the expressions of Bax and Bcl-2 gene were also detected. The results of histological HE, Masson and reticular fiber staining showed that compared with group B, the degree of inflammation and fibrosis of the tissue were statistically reduced in group C. Compared with sub-group B and C, the degree of reduce inflammation of the liver and inhibit hepatic fibrosis were more obviously with the extension of treatment time. The inflammatory activity and liver fibrosis score were statistical significant between groups (P<0.05), the highest score was group B, followed by group C. The apoptosis cells were similar between fibrotic model group and IL-7 intervention group, while the HSC count was obviously higher in group B compared to the other two groups. The Bax gene was up-regulated when intervened with IL-7 for hepatic fibrosis and Bcl-2 showed to the contrary. IL-7 could inhibit hepatic fibrosis in mice induced by CCL4 and reduce liver inflammation process. The anti-fibrosis mechanism might be involved in inducing apoptosis through P53 pathway regulated Bcl-2 and Bax genes. (AU)

Large-scale long terminal repeat insertions produced a significant set of novel transcripts in cotton.

Genomic analysis has revealed that the 1,637-Mb Gossypium arboreum genome contains approximately 81% transposable elements (TEs), while only 57% of the 735-Mb G. raimondii genome is occupied by TEs. In this study, we investigated whether there were unknown transcripts associated with TE or TE fragments and, if so, how these new transcripts were evolved and regulated. As sequence depths increased from 4 to 100 G, a total of 10,284 novel intergenic transcripts (intergenic genes) were discovered. On average, approximately 84% of these intergenic transcripts possibly overlapped with the long terminal repeat (LTR) insertions in the otherwise untranscribed intergenic regions and were expressed at relatively low levels. Most of these intergenic transcripts possessed no transcription activation markers, while the majority of the regular genic genes possessed at least one such marker. Genes without transcription activation markers formed their+1 and -1 nucleosomes more closely (only (117±1.4)bp apart), while twice as big spaces (approximately (403.5±46.0) bp apart) were detected for genes with the activation markers. The analysis of 183 previously assembled genomes across three different kingdoms demonstrated systematically that intergenic transcript numbers in a given genome correlated positively with its LTR content. Evolutionary analysis revealed that genic genes originated during one of the whole-genome duplication events around 137.7 million years ago (MYA) for all eudicot genomes or 13.7 MYA for the Gossypium family, respectively, while the intergenic transcripts evolved around 1.6 MYA, resultant of the last LTR insertion. The characterization of these low-transcribed intergenic transcripts can facilitate our understanding of the potential biological roles played by LTRs during speciation and diversifications.

The hepatoprotective effect of aspirin on carbon tetrachloride­induced hepatic fibrosis via inhibition of TGFß­1 pathway and pro­inflammatory cytokines IL­1ß and COX­2 in rats.

Aspirin decreases liver fibrosis index and inflammation levels. However, the exact mechanism underlying the effects of aspirin are yet to be elucidated. The aim of the study was to investigate the potential protective effects of aspirin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in Sprague-Dawley rats. Rats were divided into four groups, including healthy and CCl4 control and low-(aspirin 10 mg/kg + CCl4) and high-dose aspirin group (aspirin 300 mg/kg + CCl4). After 8 weeks treatment, the histopathological examinations of hepatocyte fibrosis in liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-1ß, transforming growth factor-ß1 (TGF-ß1), hyaluronic acid (HA), laminin (LN) and type IV collagen (IV.C) were determined. Histopathological examination suggested that aspirin decreased CCl4-induced hepatic fibrosis and liver inflammation. The high-dose aspirin group significantly decreased the serum levels of ALT, AST, HA and LN compared with the CCl4 control group. High-dose aspirin group significantly decreased the levels of pro-inflammatory cytokines IL-1ß compared with CCl4 group. The high-dose aspirin group significantly inhibited the expression of TGFß-1 protein compared with CCl4 group. Overall, the present study indicated that aspirin exhibited potent protective effects against CCl4-induced hepatic fibrosis via inhibition of the TGFß-1 pathway and pro-inflammatory cytokine IL-1ß.

Characteristics and symptomatology of major depressive disorder with atypical features from symptom to syndromal level.

OBJECTIVE: To explore clinical characteristics and symptomatology of major depressive disorder (MDD) with atypical features based on DSM criteria or only reversed vegetative symptoms. METHOD: A total of 3187 patients who met DSM-IV TR criteria for MDD were enrolled. Demographics and symptomatology covering multiple symptom domains were assessed and compared between three groups of cases: those who met DSM criteria for atypical specifier (the DAD group), those who had at least one reversed vegetative symptoms (hypersomnia or hyperphagia) (the SAD group) without meeting DSM atypical specifier criteria, and those without any reversed vegetative symptoms (the NAD group). RESULTS: The DAD and SAD group accounted for 4.4% and 14.4% of the participants, respectively. The DAD cases were characterized by a highest proportion of hospitalizations, longest duration of current episode and worst quality of life. The DAD and SAD cases were more likely to adopt unhealthy behaviors (smoking and alcohol drinking). Most depressive symptoms related to higher illness severity and treatment resistance were more frequent in the DAD cases, followed by the SAD cases, and least frequent in the NAD cases. LIMITATIONS: A cross-sectional design and a non-validated questionnaire were used. CONCLUSIONS: The findings support the role of DSM defined atypical depression as a valid MDD subtype and provide evidence for clinical utility of the simplified approach of defining atypical features based on only reversed vegetative symptoms. This has implications for illness screening, public health, suicide prevention and better treatment planning for depressed individuals with atypical features even below syndromal level.

Clinical Guideline (CANMAT 2016) Discordance of Medications for Patients with Major Depressive Disorder in China.

Objective: This survey aims to explore the current medical treatment of major depressive disorder (MDD) in China and match its degree with Canadian Network for Mood and Anxiety Treatments (CANMAT). Methods: A total of 3275 patients were recruited from 16 mental health centers and 16 general hospitals in China. Descriptive statistics presented the total number and percentage of drugs, as well as all kinds of treatments. Results: Selective serotonin reuptake inhibitors (SSRIs) accounted for the largest proportion (57.2%), followed by serotonin-noradrenaline reuptake inhibitors (SNRIs) (22.8%) and mirtazapine (7.0%) in the first therapy, while that of SNRIs (53.9%) followed by SSRIs (39.2%) and mirtazapine (9.8%) in the follow-up therapy. An average of 1.85 medications was administered to each MDD patient. Conclusion: SSRIs were the first choice in the first therapy, while the proportion of those drugs decreased during the follow-up therapy and were replaced by SNRIs. Plenty of combined pharmacotherapies were directly selected as the first trial of patients, which was inconsistent with guideline recommendations.

Effect of acupuncture on neuroinflammation in animal models of Alzheimer's disease: A preclinical systematic review and meta-analysis.

Background: Despite neuroinflammation being an important component of the pathology of Alzheimer's disease (AD), effective therapies to alleviate neuroinflammation are still lacking. Many animal experiments in AD have found that acupuncture may ameliorate cognition by decreasing neuroinflammation and modulating cytokines, but its effects have not been systematically examined. We aimed to assess its efficacy on neuroinflammation in AD and to investigate the potential mechanisms. Materials and methods: The following databases were searched from inception until 24 August 2022: Web of Science, EMBASE, PubMed, the Cochrane Library, and China National Knowledge Infrastructure. Animal studies that reported the efficacy of acupuncture on neuroinflammation in AD were included. The SYRCLE Robt was utilized to evaluate methodological quality. Stata 17 was utilized to conduct a meta-analysis of cytokine levels and the results of the Morris water maze. Results: 23 studies were included, with a total of 417 rats/mice. The overall quality of all included reports was medium. The results indicated that acupuncture significantly reduced the expressions of pro-inflammatory cytokines which included IL-1ß [SMD = -3.50, 95% CI (-4.31, -2.69); I 2 = 78.6%] (P < 0.05), TNF-α [SMD = -3.05, 95% CI (-3.86, -2.24); I 2 = 69.6%] (P < 0.05), IL-6 [SMD = -3.22, 95% CI (-4.62, -1.81); I 2 = 77.6%] and enhanced the expressions of anti-inflammatory cytokines including IL-4 [SMD = 2.77, 95% CI (1.95, 3.59); I 2 = 33.9%] (P < 0.05), IL-10 [SMD = 1.84, 95% CI (1.20, 2.49); I 2 = 41.0%] (P < 0.05) in an animal model of AD. Regarding the Morris water maze, compared to the control group, the acupuncture group showed a shorter escape latency [SMD = -2.23, 95% CI (-2.89, -1.57); I 2 = 79.2%] (P < 0.05), longer duration in platform quadrant [SMD = 2.34, 95% CI (1.44, 3.23); I 2 = 81.7%] (P < 0.05), and increased platform crossing number [SMD = 2.79, 95% CI (2.06, 3.53); I 2 = 71.9%] (P < 0.05). Conclusion: Acupuncture may reduce neuroinflammation in AD by modulating cytokine expression. This modulation significantly improved cognitive function in animal models of AD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354878.

Identification of potential serum biomarkers for congenital heart disease children with pulmonary arterial hypertension by metabonomics.

BACKGROUND: Pulmonary arterial hypertension is a common complication in patients with congenital heart disease. In the absence of early diagnosis and treatment, pediatric patients with PAH has a poor survival rate. Here, we explore serum biomarkers for distinguishing children with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) from CHD. METHODS: Samples were analyzed by nuclear magnetic resonance spectroscopy-based metabolomics and 22 metabolites were further quantified by ultra-high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Serum levels of betaine, choline, S-Adenosyl methionine (SAM), acetylcholine, xanthosine, guanosine, inosine and guanine were significantly altered between CHD and PAH-CHD. Logistic regression analysis showed that combination of serum SAM, guanine and N-terminal pro-brain natriuretic peptide (NT-proBNP), yielded the predictive accuracy of 157 cases was 92.70% with area under the curve of the receiver operating characteristic curve value of 0.9455. CONCLUSION: We demonstrated that a panel of serum SAM, guanine and NT-proBNP is potential serum biomarkers for screening PAH-CHD from CHD.

A drug screening to identify novel combinatorial strategies for boosting cancer immunotherapy efficacy.

BACKGROUND: Chimeric antigen receptor (CAR) T cells and immune checkpoint blockades (ICBs) have made remarkable breakthroughs in cancer treatment, but the efficacy is still limited for solid tumors due to tumor antigen heterogeneity and the tumor immune microenvironment. The restrained treatment efficacy prompted us to seek new potential therapeutic methods. METHODS: In this study, we conducted a small molecule compound library screen in a human BC cell line to identify whether certain drugs contribute to CAR T cell killing. Signaling pathways of tumor cells and T cells affected by the screened drugs were predicted via RNA sequencing. Among them, the antitumor activities of JK184 in combination with CAR T cells or ICBs were evaluated in vitro and in vivo. RESULTS: We selected three small molecule drugs from a compound library, among which JK184 directly induces tumor cell apoptosis by inhibiting the Hedgehog signaling pathway, modulates B7-H3 CAR T cells to an effector memory phenotype, and promotes B7-H3 CAR T cells cytokine secretion in vitro. In addition, our data suggested that JK184 exerts antitumor activities and strongly synergizes with B7-H3 CAR T cells or ICBs in vivo. Mechanistically, JK184 enhances B7-H3 CAR T cells infiltrating in xenograft mouse models. Moreover, JK184 combined with ICB markedly reshaped the tumor immune microenvironment by increasing effector T cells infiltration and inflammation cytokine secretion, inhibiting the recruitment of MDSCs and the transition of M2-type macrophages in an immunocompetent mouse model. CONCLUSION: These data show that JK184 may be a potential adjutant in combination with CAR T cells or ICB therapy.