MdMYB44-like positively regulates salt and drought tolerance via the MdPYL8-MdPP2CA module in apple.

Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44-like, an R2R3-MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44-like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling-mediated salt and drought tolerance. Furthermore, we found that MdMYB44-like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44-like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44-like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44-like-MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44-like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44-like precisely modulates ABA-mediated salt and drought tolerance in apples through the MdPYL8-MdPP2CA module.

Acetylcholine muscarinic M1 receptors in the rodent prefrontal cortex modulate cognitive abilities to establish social hierarchy.

In most social species, the attainment of social dominance is strongly affected by personality traits. Dominant individuals show better cognitive abilities, however, whether an individual's cognition can determine its social status has remained inconclusive. We found that mice show better cognitive abilities tend to possess a higher social rank after cohousing. The dynamic release of acetylcholine (ACh) in the prelimbic cortex (PL) is correlated with mouse dominance behavior. ACh enhanced the excitability of the PL neurons via acetylcholine muscarinic M1 receptors (M1). Inhibition of M1 impaired mice cognitive performance and induced losing in social competition. Mice with M1 deficiency in the PL performed worse on cognitive behavioral tests, and exhibited lower status when re-grouped with others. Elevating ACh level in the PL of subordinate mice induced winning. These results provide direct evidence for the involvement of M1 in social hierarchy and suggest that social rank can be tuned by altering cognition through cholinergic system.

Clinical efficacy of the mulligan maneuver for cervicogenic headache: a randomized controlled trial.

Cervicogenic headache is an often observed secondary headache in clinical settings, with patients who endure prolonged and persistent pain being particularly susceptible to mood changes. Currently, the Mulligan is one of the effective methods for CEH. However, there is a lack of evaluation about the strength and frequency of headaches, as well as the assessment of pain-induced emotions, in individuals with CEH using this particular procedure. Herein, we aimed to evaluate the effectiveness of the Mulligan maneuver from a multidimensional perspective of pain intensity and mood. A total of forty patients diagnosed with CEH who satisfied the specified inclusion criteria were recruited and allocated randomly into two groups: the control group and the treatment group, with each group consisting of twenty cases. The control group received health education, while the treatment group received the Mulligan maneuver once daily over a course of 10 treatment sessions.The clinical outcome of patients with CEH in two groups was assessed using the Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Resting-state functional magnetic resonance imaging was employed to examine variations in brain function activities between the two CEH groups. Brain regions showing differences were identified as regions of interest and subsequently correlated with clinical behavioral measures using Pearson's correlation analysis. The differences in VAS, HAMA and HAMD between the two groups of CEH patients were also statistically significant. The brain regions that showed differences in the ReHo scores between the two groups of CEH patients included the left cerebellum, the frontal gyrus, and the middle temporal gyrus. There was a positive correlation between the left frontal gyrus and VAS, HAMA and HAMD. The left middle temporal gyrus had a negative correlation with VAS, HAMA, and HAMD and the left cerebellum had a positive correlation with VAS correlation. The Mulligan maneuver may improve pain levels and have a moderating effect on pain-related negative emotions by regulating the function of relevant brain regions in CEH patients.

Pyroptosis: the dawn of a new era in endometrial cancer treatment.

Endometrial cancer (EC) is a malignancy of the inner epithelial lining of the uterus. While early-stage EC is often curable through surgery, the management of advanced, recurrent and metastatic EC poses significant challenges and is associated with a poor prognosis. Pyroptosis, an emerging form of programmed cell death, is characterized by the cleavage of gasdermin proteins, inducing the formation of extensive gasdermin pores in the cell membrane and the leakage of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), consequently causing cell swelling, lysis and death. It has been found to be implicated in the occurrence and progression of almost all tumors. Recent studies have demonstrated that regulating tumor cells pyroptosis can exploit synergies function with traditional tumor treatments. This paper provides an overview of the research progress made in molecular mechanisms of pyroptosis. It then discusses the role of pyroptosis and its components in initiation and progression of endometrial cancer, emphasizing recent insights into the underlying mechanisms and highlighting unresolved questions. Furthermore, it explores the potential value of pyroptosis in the treatment of endometrial cancer, considering its current application in tumor radiotherapy, chemotherapy, targeted therapy and immunotherapy.

D-D and PLR, NLR combined forecasting first-line treatment: The short-term curative effect and prognosis of patients with SCLC.

The aim of this study was to evaluate the difference in D-dimer (D-D) combined with the platelet lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before treatment in small cell lung cancer (SCLC) patients receiving first-line treatment and to analyze the efficacy and prognosis. We retrospectively collected the records of SCLC patients treated in our hospital from February 2019 to January 2023 and finally included 100 patients. A binary logistic regression analysis method was applied to analyze the relationship between D-D, PLR, and NLR and short-term efficacy. Univariate and multivariate Cox regression analyses were utilized to estimate the individual effect of plasma parameters on progression-free survival (PFS). The optimal cutoff values of D-D, PLR, and NLR for predicting survival outcome were determined by receiver operating characteristic curve analysis. Kaplan-Meier survival analysis was utilized to examine the correlation between D-D, PLR, and NLR the prognosis of SCLC patients. PLR was associated with a short-term curative effect in patients with SCLC (odds ratio: 0.326, 95% confidence interval [CI]: 0.135 0.790). Univariate Cox regression showed that D-D (hazard ratio [HR]: 0.495, 95% CI: 0.323-0.758), PLR (HR:0.420, 95% CI: 0.269-0.655) and NLR (HR: 0.407, 95% CI: 0.263-0.630) were associated with PFS in SCLC patients (P < .05). Multivariate Cox regression analysis showed that PLR (HR: 2.395, 95% CI: 1.468-3.906) and NLR (HR: 2.148, 95% CI: 1.319-3.499) correlated significantly with PFS (P < .05). The optimal cutoff values of D-D, PLR and NLR for predicting PFS were 0.88 mg/L (65.4% and 68.7%), 195.44 (61.5% and 81.2%) and 3.63 (63.5% and 81.2%), respectively, and the corresponding area under receiver (AUC) operating characteristic curve 0.691 (95% CI: 0.587-0.795), 0.721 (95% CI: 0.620-0.822) and 0.714 (95% CI: 0.614-0.815). When D-D was used in combination with PLR or NLR, the corresponding AUCs were 0.737 (95% CI: 0.640-0.835) and 0.761 (95% CI: 0.667-0.855). Pretreatment PLR is an independent predictor of short-term efficacy in SCLC patients. Pretreatment D-D, PLR and NLR are potential biochemical markers for predicting the prognosis of SCLC patients treated with first-line treatment. When D-D is combined with PLR and NLR, it shows stronger predictive ability.

Dissecting the efficacy of the use of acupuncture and Chinese herbal medicine for the treatment of premature ovarian insufficiency (POI): A systematic review and metaanalysis.

Premature ovarian insufficiency is a multi-factor gynecological disease that has become a major global health problem. In recent years, several trials have explored the treatment of premature ovarian insufficiency using Chinese herbal medicine and acupuncture, but the efficacy and safety of this combination remains controversial. This systematic review and meta-analysis aimed to comprehensively evaluate the efficacy and safety of combining Chinese herbal medicine with acupuncture to treat premature ovarian insufficiency. From eight different databases, we retrieved randomized controlled trials wherein Chinese herbal medicine and acupuncture had been compared with western medicine in the treatment of premature ovarian insufficiency. The bias risk assessment stipulated by the Cochrane Collaboration's tool was utilized to evaluate the quality of the chosen randomized controlled trials. This meta-analysis was executed with the help of Review Manager 5.3 and Stata 10.0. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A total of 10 randomized controlled trials involving 594 premature ovarian insufficiency patients were included in the analysis. Compared with western medicine, co-treatment with acupuncture and Chinese herbal medicine exhibited a significantly higher total effective rate (relative risk: 1.21; 95% confidence interval: 1.12-1.31; P < 0.01, I2 = 0%), but lower levels of luteinizing hormone (standardized mean difference: -0.57; 95% confidence interval: -1.06, -0.08; P < 0.05, I2 = 80%), follicle-stimulating hormone, and Kupperman index score. Moreover, the combined intervention increased estradiol level in the serum. Overall, the data demonstrate that acupuncture plus Chinese herbal medicine is an efficacious and safe treatment option for POI patients. These findings must be verified by conducting large-scale, multicenter, high-quality, and long-term randomized controlled trials.

Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke.

BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

Quantitative study of the effects of early standardized ambulation on sleep quality in patients after hepatectomy.

Background: Sleep quality has been always an important problem for patients after hepatectomy. The main purpose of the study is to investigate the effects of early ambulation on sleep quality in patients after liver resection via a quantitative study. Methods: Patients undergoing liver tumor resection were randomly divided into two groups, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess the postoperative activities and sleep quality. Results: Patients who started early ambulation after liver resection had significantly better sleep quality, faster recovery of gastrointestinal function and shorter lengths of postoperative hospital stay compared with the control group. And there was no significant difference in the incidence of postoperative complications between the two groups. Conclusion: Early standardized physical activities are feasible for patients after liver resection, which can significantly improve patient's sleep quality, reduce patient's pain and the nursing workload, and achieve rapid recovery.

Long-day photoperiods affect expression of OPN5 and the TSH-DIO2/DIO3 pathway in Magang goose ganders.

This study sought to understand the regulation mechanism of OPN5 through the TSH-DIO2/DIO3 pathway mediated photoperiod on the breeding activity of short-day breeding birds. In this study, the reproductive activity of Magang goose was regulated by artificial light, and the reproductive activity of the ganders were determined according to the daily laying rate of female geese. The testicular development and the serum reproductive hormone concentrations of ganders were measured during the reproductive period (d 0), the reproductive degeneration period (d 13 and 27) and the resting period (d 45). The mRNA and protein expression patterns of OPN5, the HPG axis reproductive genes, and TSH-DIO2/DIO3 pathway related genes were examined. Results showed that the laying rate of geese and the gonadal indices (GSI) decreased gradually after the photoperiod increased. Histological observation found that the spermatogenic function of the testis was normal on d 0 and 13, while degeneration occurred by d 27 and 45. Serum testosterone, FSH, and LH concentration showed a slight increase on d 13, followed by a sharp decrease on d 27 and 45 (P < 0.01), while PRL concentrations were low on d 0 and 13, and increased rapidly on d 27 and 45 (P < 0.01).The expression pattern of GnRH, FSH, LH, and THRß mRNA were similar, with high levels on d 0 and 13 and a decreasing trend on d 27 and 45 (P < 0.05 or P < 0.01); and GnRHR mRNA levels were higher on d 13 (P < 0.05), but then had decreased by d 27 and 45 (P < 0.01). The expression pattern of GnIH and GnIHR was similar, which was opposite to that of GnRHR. VIP, PRL, and PRLR increased gradually and peaked on d 45 (P < 0.01). The expression trend of TRH, TSHß, and DIO2 was similar to that of GnRHR, and the expression abundance increased on d 13, and then decreased on d 27 and 45. GnRH protein expression was significantly higher than during the other 3 periods (P < 0.01) while the GnIH protein levels were extremely low on d 0, had gradually increased by d 13, and significantly increased by d 27 and 45 (P < 0.01). The protein expression trends of THR and DIO2 were similar to that of GNIH. DIO3 protein expression was low on d 0 and 13, and increased by d 27 and 45. These results suggest that when the photoperiod increased, the hypothalamus OPN5 gene and protein were upregulated and the pituitary TSHß, TSHR, and hypothalamus THRß, TRH, and DIO2 were downregulated, and thus the reproductive activity of geese was inhibited.

miRNA-124 regulates palmitic acid-induced epithelial-mesenchymal transition and cell migration in human retinal pigment epithelial cells by targeting LIN7C.

The present study revealed that palmitic acid (PA) treatment induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, which are involved in the progression of proliferative vitreoretinopathy (PVR). ARPE-19 cells were treated with PA followed by miRNA screening and EMT marker detection using qRT-PCR. Then, miR-124 mimic or inhibitor was transfected into ARPE-19 cells to explore the role of miR-124 on the EMT of ARPE-19 cells using transwell assay. The underlying mechanism of miRNA were predicted by bioinformatics method and confirmed by luciferase activity reporter assay. Furthermore, gain-of-function strategy was also used to explore the role of LIN7C in the EMT of ARPE-19 cells. The expression of miRNA or mRNA expression was determined by qRT-PCR and the protein expression was determined using western blot assay. The result presented that PA reduced the expression of E-cadherin/ZO-1 whilst increasing the expression of fibronectin/α-SMA. In addition, PA treatment enhanced the expression of microRNA (miR)-124 in ARPE-19 cells. Overexpression of miR-124 enhanced PA-induced upregulation of E-cadherin and ZO-1 expression and downregulation of fibronectin and α-SMA. Moreover, miR-124 mimic also enhanced the migration of ARPE-19 cells induced by PA treatment. Inversely, miR-124 inhibitor presented opposite effect on PA-induced EMT and cell migration in ARPE-19 cells. Luciferase activity reporter assay confirmed that Lin-7 homolog C (LIN7C) was a direct target of miR-124 in ARPE-19 cells. Overexpression of LIN7C was found to suppress the migration ability and expression of fibronectin and α-SMA, while increasing expression of E-cadherin and ZO-1; miR-124 mimic abrogated the inhibitive effect of LIN7C on the EMT of ARPE-19 cells and PA further enhanced this abolishment. Collectively, these findings suggest that miR-124/LIN7C can modulate EMT and cell migration in RPE cells, which may have therapeutic implications in the management of PVR diseases.

Comparison of predictive value of risk scores for gastrointestinal bleeding in antiplatelet therapy.

Gastrointestinal bleeding (GIB) is the most common serious bleeding complication of antiplatelet therapy. The bleeding risk score (BRS) of GIB may help to determine the risk of bleeding, and provides a reference for the formulation of antiplatelet therapy regimen in clinical practice, but we found that no specific risk scores are available in East Asian patients. This study analyzed patients who were administered antiplatelet therapy from May 2015 to December 2018 in two medical centers. Patient's baseline data were obtained. We assessed four BRSs (New Score, RIETE Score, Cuschieri Score, de Groot Score) and compared them using the area under the receiver operating characteristic curve (AUC). The 4,052 patients enrolled in this study had an average age of 69.6 ± 10.8 years, and 65.9% of them were male. Among the 4,052 patients included, 171 patients experienced GIB within 6 months of follow-up. In the study population, the AUCs for the New, RIETE, Cuschieri, and de Groot scores were 0.673 (95% confidence interval (CI) 0.616-0.729, P < .001), 0.742 (95% CI 0.690-0.794, P < .001), 0.598 (95% CI 0.537-0.659, P = .002), and 0.875 (95% CI 0.839-0.912, P < .001), respectively. After validation, the de Groot Score has better performance. Among the four scores, the de Groot Score might be more suitable for helping Chinese clinicians to predict the risk of GIB in patients taking antiplatelet drugs, and reduce GIB events.

Systemic lupus erythematosus patients have a distinct structural and functional skin microbiota compared with controls.

OBJECTIVE: The skin is the second most affected organ after articular involvement in systemic lupus erythematosus (SLE) patients. Cutaneous involvement occurs in approximately 80% of patients during the course of SLE. Interaction between the host and skin microorganism is a complex process. There are few studies on the diversity of skin microbes in SLE patients. Therefore, this study aims to explore the relationship between skin microorganisms and SLE. METHODS: A total of 20 SLE patients, 20 controls with rosacea and 20 healthy controls were selected as study subjects. Both the skin microbiota of rash region and non-rash region for each SLE patient were collected.16S rRNA gene sequencing was used to detected skin microbiota from 80 specimens. α-Diversity and ß-diversity of skin microbiota were analyzed based on operational taxonomic units (OTUs) and minimal entropy decomposition (MED). Using Wilcoxon test and Linear Discriminate Analysis Effect Size (LEfSe), skin microbial diversity and composition were analyzed. Functional capabilities of microbiota were estimated through Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Compared to rash region of SLE, diversity and richness were increased in healthy controls, and decreased in non-rash region of SLE and rash region of controls with rosacea. Additionally, changes of skin microbial composition were found at different taxonomic levels between four groups. For example, genus Halomonas was increased and genera Pelagibacterium, Novosphingobium, and Curvibacter were decreased in rash region compared to non-rash region of SLE based on OTUs and MED. Based on OTUs, metabolic pathways were also found differences in SLE patients, such as Xenobiotics Biodegradation and Metabolism. CONCLUSION: Compositions and diversity of skin microbiota in SLE patients are changed. This pilot study provides some suggestive evidence for further exploration of skin microbiota in SLE patients with cutaneous involvement.

The efficiency and safety of manual therapy for cervicogenic cephalic syndrome (CCS): A systematic review and meta-analysis.

BACKGROUND: Manual therapy is a common technique for the treatment of (CCS) cervicogenic cephalic syndrome, but the efficiency is various. The aim of the study is to evaluate the evidence pertaining to the efficiency and safety of using manual therapy to treat patients with CCS. METHODS: We searched the electronic databases including PubMed, ScienceDirect, and the Cochrane Library. Only randomized controlled trials (RCTs) were enrolled in this systematic review and cumulative meta-analysis. RESULTS: A total of 8 RCTs with 395 patients were included for meta-analysis. Patients who underwent manual therapy showed lower scores of visual analog scale (VAS) (weighted mean difference) WMD = 1.7, 95% confidence interval CI = 0.74-2.65, P = .0005); dizziness handicap inventory (DHI) (WMD = 0.66, 95%CI = 0.31-1, P = .0002); and neck disability index (NDI) (WMD = 0.59, 95%CI = 0.23-0.96, P = .002) and better rotation range of motion (ROM) of the cervical spine (WMD = -6.54, 95%CI = -7.60 to -5.48, P < .0001). However, these patients did not show much benefit from manual therapy with respect to the frequency of CCS episodes and head repositioning accuracy (HRA). No serious adverse effects were reported in our included studies lasting longer than 24 hours. CONCLUSIONS: Manual therapy offers an effective and safe approach to treat CCS with lower VAS, DHI, and NDI scores and better cervical spinal movement. Further high-quality RCTs are required to provide more conclusive evidence. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO172740.

Comparison of clinical performance of four gastrointestinal bleeding risk scores in Chinese patients with atrial fibrillation receiving oral anticoagulants.

Gastrointestinal bleeding is the most common bleeding complication during anticoagulant therapy. A reliable bleeding risk score can help the clinician assess risk of bleeding in individual patients and select the anticoagulant regimen. This study retrospectively analyzed the data of patients with atrial fibrillation who received anticoagulant therapy from July 2015 to December 2018 at two centers-the Fujian Medical University Union Hospital and Fuzhou Second Hospital Affiliated to Xiamen University. Demographic data, clinical findings, and laboratory results were collected from the hospital records. Patients were followed up for 6 months. The performance of four bleeding risk scores (New Score, RIETE Score, Cuschieri et al. Score, de Groot et al. Score) for prediction of gastrointestinal bleeding was assessed using the area under the curve. A total of 3462 patients (mean age, 66.3 ± 11.5 years; 59.6% males; 1055 direct oral anticoagulants users and 2407 warfarin users) were followed up for 6 months. While 99/3462 (2.9%) patients had gastrointestinal bleeding. The area under the curves for the New, RIETE, Cuschieri et al., de Groot et al. scores were 0.652 (95% CI 0.576-0.728), 0.862 (95% CI 0.809-0.914), 0.606 (95% CI 0.527-0.685), and 0.873 (95% CI 0.816-0.929), respectively. Among the four BRSs evaluated, the RIETE score and the de Groot et al. score appear to have the good predictive value, while the NEW score and the Cuschieri et al. score did not sufficiently predict gastrointestinal bleeding risk within the study Chinese population.

Prognostic value of ECOG performance status and Gleason score in the survival of castration-resistant prostate cancer: a systematic review.

Eastern Cooperative Oncology Group (ECOG) performance status and Gleason score are commonly investigated factors for overall survival (OS) in men with castration-resistant prostate cancer (CRPC). However, there is a lack of consistency regarding their prognostic or predictive value for OS. Therefore, we performed this meta-analysis to assess the associations of ECOG performance status and Gleason score with OS in CRPC patients and compare the two markers in patients under different treatment regimens or with different chemotherapy histories. A systematic literature review of monotherapy studies in CRPC patients was conducted in the PubMed database until May 2019. The data from 8247 patients in 34 studies, including clinical trials and real-world data, were included in our meta-analysis. Of these, twenty studies reported multivariate results and were included in our main analysis. CRPC patients with higher ECOG performance statuses (≥ 2) had a significantly increased mortality risk than those with lower ECOG performance statuses (<2), hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.68-2.62, and P < 0.001. The synthesized HR of OS stratified by Gleason score was 1.01, with a 95% CI of 0.62-1.67 (Gleason score ≥ 8 vs <8). Subgroup analysis showed that there was no significant difference in pooled HRs for patients administered taxane chemotherapy (docetaxel and cabazitaxel) and androgen-targeting therapy (abiraterone acetate and enzalutamide) or for patients with different chemotherapy histories. ECOG performance status was identified as a significant prognostic factor in CRPC patients, while Gleason score showed a weak prognostic value for OS based on the available data in our meta-analysis.

Metabolite and Microbiome Profilings of Pickled Tea Elucidate the Role of Anaerobic Fermentation in Promoting High Levels of Gallic Acid Accumulation.

Gallic acid (GA) is an important active ingredient for its pharmacological activities. High levels of GA in tea can be obtained by anaerobic fermentation, but its mechanism is still unclear. Here, the profiles of metabolites and microbiomes in pickled tea were analyzed. The results showed that GA of pickled tea increased to 24.26 mg/g at 18 d after anaerobic fermentation, which was accompanied by the reducing levels of epicatechin gallate (ECG), epiafzelechin-3-O-gallate (EAG), and 7-galloylcatechin (7-GC) and the increasing relative abundances of Bacillus and other six bacterial genera. However, epigallocatechin gallate (EGCG) was basically stable during the whole fermentation process. These results suggested that EGCG contributes little to the GA formation during anaerobic fermentation, but ECG, EAG, and 7-GC should be the key precursors to form GA; moreover, bacteria, especially Bacillus, may be responsible for their bioconversion. It will establish an effective way to increase GA in tea production.

Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

OBJECTIVE: We carried out this systematic review and meta-analysis to evaluate the effectiveness of TKABP on POI. METHODS: The following eight databases were searched from the establishment to September 30, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Twenty-three RCTs involving 1712 patients with POI were included. Compared to hormone therapy (HT) groups, TKABP groups showed a significantly higher total effective rate (RR: 1.10; 95% CI: 1.04-1.17; P < 0.01, I 2 = 32%). In addition, TKABP groups revealed a better improvement in terms of serum follicle-stimulating hormone (FSH) levels, serum estradiol (E2) levels, peak systolic velocity (PSV) of ovarian stromal blood, and Kupperman index (KI) score. However, serum luteinizing hormone (LH) levels and ovarian volume (OV) showed no significant statistical difference. Subgroup analyses showed that herbal paste and 3 months of treatment duration had a greater effect on the improvement of hormone levels. Besides, the occurrence of related adverse events in TKABP groups was lower than that in HT groups. CONCLUSIONS: Our review suggests that TKABP appears to be an effective and safe measure for patients with POI, and the herbal paste may be superior. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with furthermore standardized researches of rigorous design.

Dysbiosis of oral microbiota is associated with systemic lupus erythematosus.

OBJECTIVE: The important role of intestinal microbiota in systemic lupus erythematosus (SLE) has been recognized. Oral-gut microbiome axis is a crucial link in human health and disease, but few researches indicated the relationship between oral microorganisms and SLE. This study mainly explored the composition and changes of oral microorganisms in SLE patients with different stages, clinical manifestations and biomarkers. DESIGN: Oral microbiota was detected by 16S ribosomal RNA gene sequencing from 20 SLE patients and 19 healthy controls (HCs). The evenness, diversity and composition of oral microbiota were analyzed. Moreover, receiver-operating characteristic analysis was conducted. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to investigate microbiota functions. RESULTS: The oral microbiota of SLE patients was imbalanced and the diversity was decreased, but no difference was found between new-onset and treated SLE patients. Families Lactobacillaceae, Veillonellaceae and Moraxellaceae were enriched in SLE patients. Families like Corynebacteriaceae, Micrococcaceae, Defluviitaleaceae, Caulobacteraceae, Phyllobacteriaceae, Methylobacteriaceae, Hyphomicrobiaceae, Sphingomonadaceae, Halomonadaceae, Pseudomonadaceae, Xanthomonadaceae, etc. were decreased in SLE patients. After multiple testing adjustment, families Sphingomonadaceae, Halomonadaceae, and Xanthomonadaceae were significantly decreased in SLE patients. And area under the curve was 0.953 (95% confidence intervals 0.890-1.000) to distinguish SLE patients from HCs. There were differences in metabolic pathways between SLE and HCs (P = 0.025). CONCLUSIONS: These findings collectively support that oral microbiota dysbiosis and aberrant metabolic pathways were observed in patients with SLE. Our findings may provide suggestive evidences for the diagnosis and treatment of SLE.

ErbB4 knockdown in serotonergic neurons in the dorsal raphe induces anxiety-like behaviors.

There is a close relationship between serotonergic (5-HT) activity and anxiety. ErbB4, a receptor tyrosine kinase, is expressed in 5-HT neurons. However, whether ErbB4 regulates 5-HT neuronal function and anxiety-related behaviors is unclear. Here, using transgenic and viral approaches, we show that mice with ErbB4 deficiency in 5-HT neurons exhibit heightened anxiety-like behavior and impaired fear extinction, possibly due to an increased excitability of 5-HT neurons in the dorsal raphe nucleus (DRN). Notably, the chemogenetic inhibition of 5-HT neurons in the DRN of ErbB4 mutant mice rescues anxiety-like behaviors. Altogether, our results unravel a previously unknown role of ErbB4 signaling in the regulation of DRN 5-HT neuronal function and anxiety-like behaviors, providing novel insights into the treatment of anxiety disorders.

Liver Soluble Epoxide Hydrolase Regulates Behavioral and Cellular Effects of Chronic Stress.

Major depression is a serious global health concern; however, the pathophysiology underlying this condition remains unclear. While numerous studies have focused on brain-specific mechanisms, few have evaluated the role of peripheral organs in depression. Here, we show that the liver activates an intrinsic metabolic pathway that can modulate depressive-like behavior. We find that chronic stress specifically increases the protein levels of monomeric and oligomeric soluble epoxide hydrolase (sEH), a key enzyme in epoxyeicosatrienoic acid (EET) signaling, in the liver. Hepatic deletion of Ephx2 (which encodes sEH) results in antidepressant-like effects, while the hepatic overexpression of sEH induces depressive phenotypes. The activity of sEH in hepatocytes modulates the plasma levels of 14,15-EET, which then interacts with astrocytes in the medial prefrontal cortex to mediate the effects of hepatic Ephx2 deletion. These results suggest that targeting mechanisms underlying the hepatic response to stress would increase our therapeutic options for the treatment of depression.