Efficacy and safety of anlotinib plus anti-PD-1 agents in patients with refractory advanced biliary tract cancers.

BACKGROUND: Anlotinib has demonstrated promising anti-tumor efficacy in various solid tumors. Additionally, there is evidence suggesting that immune therapy can enhance the systemic responses of anlotinib. This study aimed to assess the effectiveness and safety of combining anlotinib with PD-1 inhibitors compared to fluoropyrimidine-based chemotherapy as a second-line treatment option for advanced biliary tract cancers (BTCs). METHODS: A total of 242 patients with BTCs were screened at the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2022. Among them, 78 patients who received either anlotinib plus PD-1 inhibitors (AP) or fluoropyrimidine-based chemotherapy (FB) as second-line treatment were included in the study. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and predictive tumor biomarkers. RESULTS: Among the 78 patients with BTCs, 39 patients received AP, while 39 patients were administered FB. The ORR in the AP group was 20.5%, compared to 5.1% in the FB group. The DCR was 87.2% in the AP group and 66.7% in the FB group. The AP group demonstrated significantly better ORR and DCR compared to the FB group (p = 0.042, p = 0.032). The median PFS and OS in the AP group were 7.9 months (95% CI: 4.35-11.45) and 13.9 months (95% CI: 5.39-22.41), respectively. In the FB group, the median PFS and OS were 4.1 months (95% CI: 3.17-5.03) and 13.2 months (95% CI: 8.72-17.68), respectively. The AP group exhibited significantly better median PFS than the FB group (p = 0.027). In the subgroup analysis, patients without liver metastasis had a much longer PFS in the AP group compared to the FB group (14.3 vs. 5.5 months, p = 0.016). Similarly, patients with CEA ≤ 5 µg/L also demonstrated a longer PFS in the AP group compared to the FB group (8.7 vs. 3.9 months, p = 0.008). CONCLUSIONS: The combination of anlotinib and PD-1 inhibitors demonstrated a promising clinical effect compared to fluoropyrimidine-based chemotherapy in the second-line treatment of refractory advanced BTCs. Liver metastases and CEA levels may serve as predictive factors for identifying patients who may benefit from AP therapy.

Characterization of potassium-solubilizing fungi, Mortierella spp., isolated from a poplar plantation rhizosphere soil.

Potassium-solubilizing microorganisms are capable of secreting acidic chemicals that dissolve and release potassium from soil minerals, thus facilitating potassium uptake by plants. In this study, three potassium-dissolving filamentous fungi were isolated from the rhizosphere soil of a poplar plantation in Jiangsu Province, China. Phylogenetic analyses based on ITS, 18 S, and 28 S showed that these three isolates were most similar to Mortierella. These strains also possessed spherical or ellipsoidal spores, produced sporangia at the hyphal tip, and formed petal-like colonies on PDA media resembling those of Mortierella species. These findings, along with further phenotypic observations, suggest that these isolates were Mortierella species. In addition, the potassium-dissolution experiment showed that strain 2K4 had a relatively high potassium-solubilizing capacity among these isolated fungi. By investigating the influences of different nutrient conditions (carbon source, nitrogen source, and inorganic salt) and initial pH values on the potassium-dissolving ability, the optimal potassium-solubilization conditions of the isolate were determined. When potassium feldspar powder was used as an insoluble potassium source, isolate 2K4 exhibited a significantly better polysaccharide aggregation ability on the formed mycelium-potassium feldspar complex. The composition and content of organic acids secreted by strain 2K4 were further detected, and the potassium-dissolution mechanism of the Mortierella species and its growth promotion effect were discussed, using maize as an example.

Pichia kurtzmaniana f.a. sp. nov., with the transfer of eight Candida species to Pichia.

Three yeast strains belonging to the ascomycetous yeast genus Pichia were isolated from two soil samples from Yunnan and Guizhou provinces and a marine water sample from Liaoning province, PR China. Phylogenetic analyses based on the sequences of the D1/D2 domains of the large subunit(LSU) rRNA gene and the internal transcribed spacer (ITS) region indicate that these three strains, together with 12 additional strains isolated from various substrates collected in different regions or countries of the world, represent a novel species of the genus Pichia, for which the name Pichia kurtzmaniana sp. nov. (holotype: strain CGMCC 2.7213) is proposed. The novel species differs from its close relatives Candida californica by eight (1.5 %) and 26 (11.1 %) mismatches in the D1/D2 domains and the ITS region, respectively; and from Pichia chibodasensis by 11 (2.1 %) and 20 (8.7 %) mismatches in the D1/D2 domains and the ITS region, respectively. In addition, eight Candida species which belong to the Pichia clade are transferred to the genus Pichia, resulting in the proposal of the following new combinations: Pichia cabralensis comb. nov., Pichia californica comb. nov., Pichia ethanolica comb. nov., Pichia inconspicua comb. nov., Pichia phayaonensis comb. nov., Pichia pseudolambica comb. nov., Pichia rugopelliculosa comb. nov., and Pichia thaimueangensis comb. nov.

Saturnispora sinensis sp. nov., a new ascomycetous yeast species from soil and rotten wood.

A yeast strain (CGMCC 2.6937T) belonging to the ascomycetous yeast genus Saturnispora was recently isolated from soil collected in Xinghuacun, Shanxi Province, PR China. The strain produces one or two ellipsoid or spherical ascospores in asci formed by the conjugation between a cell and its bud. Phylogenetic analyses of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit rRNA gene suggest that this strain is conspecific with strains NYNU 14639 isolated from rotten wood collected in Funiu Mountain, Henan province and ES13S05 from soil collected in Nantou County, Taiwan. The CGMCC 2.6937T group is most closely related to Saturnispora dispora and Saturnispora zaruensis. However, strain CGMCC 2.6937T differs from S. dispora by 17 (3.2 %, 13 substitutions and four gaps) and 77 (18.8 %, 52 substitutions and 25 gaps) mismatches, and from S. zaruensis by 15 (2.9 %, 12 substitutions and three gaps) and 64 (15.6 %, 44 substitutions and 20 gaps) mismatches, in the D1/D2 domain and ITS region, respectively. The results suggest that the CGMCC 2.6937T group represents an undescribed species in the genus Saturnispora, for which the name Saturnispora sinensis sp. nov. is proposed. The holotype strain is CGMCC 2.6937T.

[Genetic analysis of a case with Al Kaissi syndrome and a literature review].

OBJECTIVE: To explore the genetic etiology of a child with delayed growth and development and carry out a literature review. METHODS: A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy. RESULTS: The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR-agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion. CONCLUSION: The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.

Study on therapeutic mechanism of total salvianolic acids against myocardial ischemia-reperfusion injury based on network pharmacology, molecular docking, and experimental study.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salviae miltiorrhizae, also known as Danshen in Chinese, effectively activates the blood and resolves stasis. Total salvianolic acids (SA) is the main active ingredient of Danshen, and related preparations, such as salvianolate injection are commonly used clinically to treat myocardial ischemia-reperfusion injury (MIRI). However, the potential targets and key active ingredients of SA have not been sufficiently investigated. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of SA in treating MIRI. MATERIALS AND METHODS: Network pharmacology and molecular docking techniques were used to predict SA targets against MIRI. The key acting pathway of SA were validated by performing experiments in a rat MIRI model. RESULTS: Twenty potential ingredients and 54 targets of SA in treating MIRI were identified. Ingredient-target-pathway network analysis revealed that salvianolic acid B and rosmarinic acid had the highest degree value. Pathway enrichment analysis showed that SA may regulate MIRI through the IL-17 signaling pathway, and this result was confirmed in the rat MIRI experiment. CONCLUSION: The results of this study indicate that SA may protect MIRI by regulating the IL-17 pathway.

Sample preparation for fatty acid analysis in biological samples with mass spectrometry-based strategies.

Fatty acids (FAs) have attracted many interests for their pivotal roles in many biological processes. Imbalance of FAs is related to a variety of diseases, which makes the measurement of them important in biological samples. Over the past two decades, mass spectrometry (MS) has become an indispensable technique for the analysis of FAs owing to its high sensitivity and precision. Due to complex matrix effect of biological samples and inherent poor ionization efficiency of FAs in MS, sample preparation including extraction and chemical derivatization prior to analysis are often employed. Here, we describe an updated overview of FA extraction techniques, as well as representative derivatization methods utilized in different MS platforms including gas chromatography-MS, liquid chromatography-MS, and mass spectrometry imaging based on different chain lengths of FAs. Derivatization strategies for the identification of double bond location in unsaturated FAs are also summarized and highlighted. The advantages, disadvantages, and prospects of these methods are compared and discussed. This review provides the development and valuable information for sample pretreatment approaches and qualitative and quantitative analysis of interested FAs using different MS-based platforms in complex biological matrices. Finally, the challenges of FA analysis are summarized and the future perspectives are prospected.

Hydroxyl-rich ferrofluid for efficient liquid phase microextraction of cinnamic acid derivatives in traditional Chinese medicine.

In this study, a hydroxyl-rich ferrofluid was prepared by dispersing silica-coated magnetic nanoparticles into a methyltrioctylammonium chloride-glycerol deep eutectic solvent and then employed in the preconcentration of trace-level of cinnamic acid derivatives (caffeic acid, p-hydroxycinnamic acid, ferulic acid, and cinnamic acid) in traditional Chinese medicine prior to high-performance liquid chromatography analysis. The structures of the synthesized materials were characterized by X-ray diffraction and infrared spectroscopy. The experimental parameters affecting the extraction performance, such as deep eutectic solvent composition, dosage of ferrofluid, pH of aqueous sample solution, salt concentration, extraction time, type, and volume of desorption solvent, were studied and optimized. Under the optimum conditions, the enrichment factors of four cinnamic acid derivatives were in the range of 107-114. Low detection limits (0.2-0.9 ng/mL), good precisions (relative standard deviations 1.2%-9.5%), and satisfactory recoveries (96.0%-104.7%) were achieved. Subsequently, the possible microextraction mechanism of the proposed method was explored and elucidated. It showed that the prepared ferrofluid is easily dispersed in the aqueous sample and achieved recovery after the extraction. The developed approach is a simple, convenient, and efficient method for preconcentration and determination of cinnamic acid derivatives in complex matrices.

Reliability and validity of the Chinese version of the COMPI Fertility Problem Stress Scale-Short Form for infertile women.

OBJECTIVE: To translate and culturally adapt the COMPI Fertility Problem Stress Scale-Short form (COMPI-FPSS-SF) and to test its reliability and validity in China. METHODS: The cross-sectional study adopted Brislin's translation model to translate, synthesize, back-translate, and cross-culturally adapt the COMPI-FPSS-SF for the Chinese setting. A total of 279 infertile women were invited to participate in the study to test the reliability and validity of the scale between March and June 2021. RESULTS: It was verified that the Chinese version of the COMPI-FPSS-SF has three domains with nine items. The Cronbach's α coefficient of the total scale was 0.907, and the coefficient for each dimension ranged from 0.760 to 0.855. The test-retest validity was 0.891. The exploratory factor analysis extracted three common factors with eigenvalues of 4.499, 1.124, and 1.011 and a cumulative variance contribution of 73.706. The validity factor analysis showed good results for the three-factor structure fit. The criterion-related validity with the Fertility Inventory Short-Form Scale was 0.649. The above analysis revealed statistically significant differences (P < 0.001). CONCLUSIONS: The Chinese version of the COMPI-FPSS-SF can be used for the assessment of fertility-related stress in infertility patients in China with good reliability and validity.

Transcriptional patterns of the cortical Morphometric Inverse Divergence in first-episode, treatment-naïve early-onset schizophrenia.

Early-onset Schizophrenia (EOS) is a profoundly progressive psychiatric disorder characterized by both positive and negative symptoms, whose pathogenesis is influenced by genes, environment and brain structure development. In this study, the MIND (Morphometric Inverse Divergence) network was employed to explore the relationship between morphological similarity and specific transcriptional expression patterns in EOS patients. This study involved a cohort of 187 participants aged between 7 and 17 years, consisting of 97 EOS patients and 90 healthy controls (HC). Multiple morphological features were used to construct the MIND network for all participants. Furthermore, we explored the associations between MIND network and brain-wide gene expression in EOS patients through partial least squares (PLS) regression, shared genetic predispositions with other psychiatric disorders, functional enrichment of PLS weighted genes, as well as transcriptional signature assessment of cell types, cortical layers, and developmental stages. The MIND showed similarity differences in the orbitofrontal cortex, pericalcarine cortex, lingual gyrus, and multiple networks in EOS patients compared to HC. Moreover, our exploration revealed a significant overlap of PLS2 weighted genes linking to EOS-related MIND differences and the dysregulated genes reported in other psychiatric diseases. Interestingly, genes correlated with MIND changes (PLS2-) exhibited a significant enrichment not only in metabolism-related pathways, but also in specific astrocytes, cortical layers (specifically layer I and III), and posterior developmental stages (late infancy to young adulthood stages). However, PLS2+ genes were primarily enriched in synapses signaling-related pathways and early developmental stages (from early-mid fetal to neonatal early infancy) but not in special cell types or layers. These findings provide a novel perspective on the intricate relationship between macroscopic morphometric structural abnormalities and microscopic transcriptional patterns during the onset and progression of EOS.

Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns.

BACKGROUND: This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. METHODS: We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. RESULTS: Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior-posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons. CONCLUSIONS: The findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease.

Treatment of postpartum depression with integrated traditional Chinese and Western medicine nursing and electrical stimulation.

BACKGROUND: Postpartum depression (PPD) is a common psychological disease among puerperal women, and postpartum pelvic floor dysfunction is a common disease among pregnant women. The occurrence of postpartum pelvic floor dysfunction will increase the incidence of PPD. AIM: To explore the therapeutic effect of integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis on PPD. METHODS: From April 2020 to January 2022, 100 parturients with a rectus abdominis muscle separation distance > 2.0 cm who underwent reexamination 6 wk after delivery at our hospital were selected as the research subjects. According to the random number table method, the patients were divided into either an observation group (n = 50) or a control group (n = 50). There was no significant difference in the general data between the two groups (P > 0.05). Both groups were treated by electrical stimulation. The observation group was additionally treated by integrated traditional Chinese and Western medicine nursing. A self-designed Depression Knowledge Questionnaire was used to evaluate the awareness of knowledge on depression in all patients 3 wk after intervention. The Hamilton Depression Scale (HAMD) was used to evaluate the depression before intervention and 1 wk and 3 wk after intervention, and the Morisky Medication Adherence Scale (MMAS-8) was used to evaluate the medication compliance. SPSS19.0 was used for statistical analyses. RESULTS: The rate of awareness of knowledge on depression in the observation group was significantly higher than that of the control group (P < 0.05). The scores of MMAS-8 were comparable between the two groups before intervention (P > 0.05), but were significantly higher in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05). The HAMD scores were comparable between the two groups before intervention (P > 0.05), but were significantly lower in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05). CONCLUSION: Integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis is effective in the treatment of postpartum depression and worthy of clinical promotion.

Visible-Light-Mediated Catalyst-Free [2+2] Cycloaddition Reaction for Dihydrocyclobuta[b]naphthalene-3,8-diones Synthesis under Mild Conditions.

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[b]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

[Effect of somatostatin on gastrointestinal hormone levels and clinical outcomes in critically ill infants after gastrointestinal surgery: a prospective randomized controlled study]. / ç”Ÿé•¿æŠ‘ç´ å¯¹é‡ç—‡æ¶ˆåŒ–é“æœ¯åŽå©´å„¿èƒƒè‚ æ¿€ç´ æ°´å¹³å’Œä¸´åºŠé¢„åŽçš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery. METHODS: Using a random number table method, critically ill infants after gastrointestinal surgery who were admitted to the Intensive Care Unit of Xuzhou Children's Hospital from June 2019 to June 2021 were randomly divided into an observation group (29 cases) and a control group (30 cases). The control group received routine treatment such as anti-infection and hemostasis after surgery, while the observation group received somatostatin in addition to the routine treatment [3.5 µg/(kg·h) infusion for 7 days]. The levels of serum gastrin (GAS), motilin (MTL), insulin, and glucagon-like peptide-1 (GLP-1) before surgery, on the 3rd day after surgery, and on the 7th day after surgery were compared between the two groups. The recovery progress and incidence of complications after surgery were also compared between the two groups. RESULTS: There was no significant difference in the levels of serum GAS, MTL, insulin, and GLP-1 between the two groups before surgery (P>0.05). On the 3rd and 7th day after surgery, the levels of serum GAS, MTL, insulin, and GLP-1 in the observation group were higher than those in the control group (P<0.05). In the observation group, the levels of GAS, MTL, insulin, and GLP-1 on the 7th day after surgery were higher than those before surgery and on the 3rd day after surgery (P<0.05), and the levels on the 3rd day after surgery were higher than those before surgery (P<0.05). There was no significant difference in the levels of serum GAS, MTL, and insulin before surgery, on the 3rd day after surgery, and on the 7th day after surgery in the control group (P>0.05). The level of GLP-1 on the 7th day after surgery was higher than that before surgery and on the 3rd day after surgery (P<0.05), and the level on the 3rd day after surgery was higher than that before surgery (P<0.05) in the control group. The observation group had shorter first time of anal exhaust, recovery time of bowel sounds, and first time of defecation after surgery compared to the control group (P<0.05). The incidence of complications after surgery in the observation group was lower than that in the control group (10% vs 33%, P<0.05). CONCLUSIONS: Somatostatin can increase the levels of serum GAS, MTL, insulin, and GLP-1 in critically ill infants after gastrointestinal surgery, promote the recovery of gastrointestinal function, and reduce the incidence of postoperative complications.

The effect of polyvinyl chloride (PVC) color on biofilm development and biofilm-heavy metal chemodynamics in the aquatic environment.

Plastic surfaces are colonized by microorganisms and biofilms are formed in the natural aquatic environment. As the biofilm develops, it changes the density and buoyancy of the plastic-biofilm complex, results in plastic sinking, and increases the heavy metals accumulated by biofilm's mobility and availability in aquatic ecosystems. In this experiment, biofilms were cultured on five colors of polyvinyl chloride (PVC; transparent, green, blue, red, black) in an aquatic environment to investigate the effects of plastic color on biofilm formation and development (Phase 1) and to study the effects of being sunk below the photic zone on biofilm (Phase 2). The PVC color significantly affected the biofilm formation rate but had no impact on the final biofilm biomass. After sinking the biofilm-PVC below the photic zone in Phase 2, the layer of diatoms on the biofilm surface began to disintegrate, and the biomass and Chlorophyll-a (Chla) content of the biofilm decreased, except on the red PVC. Below the photic zone, the microbial community of the biofilm changed from primarily autotrophic microbes to mostly heterotrophic microbes. Microbial diversity increased and extracellular polymeric substances (EPS) content decreased. The primary factor leading to microbial diversity and community structure changes was water depth rather than PVC color. The changes induced in the biofilm led to an increase in the concentration of all heavy metals in the biofilm, related to the increase in microbial diversity. This study provides new insights into the biofilm formation process and the effects on a biofilm when it sinks below the photic zone.

Protective effect of paeoniflorin in diabetic nephropathy: A preclinical systematic review revealing the mechanism of action.

BACKGROUND: Paeoniflorin (PF), the main active glucoside of Paeonia Lactiflora, has many pharmacological activities, such as inhibition of vasodilation, hypoglycemia, and immunomodulation. Although the current evidence has suggested the therapeutic effects of PF on diabetic nephropathy (DN), its potential mechanism of action is still unclear. PURPOSE: A systematic review and meta-analysis of the existing literature on paeoniflorin treatment in DN animal models was performed to evaluate the efficacy and mechanism of PF in DN animal models. METHODS: The risk of bias in each study was judged using the CAMARADES 10-item quality checklist with the number of criteria met varying from 4 / 10 to 7 / 10, with an average of 5.44. From inception to July 2022, We searched eight databases. We used the Cochrane Collaboration's 10-item checklist and RevMan 5.3 software to assess the risk of bias and analyze the data. Three-dimensional dose/time-effect analyses were conducted to examine the dosage/time-response relations between PF and DN. RESULTS: Nine animal studies were systematically reviewed to evaluate the effectiveness of PF in improving animal models of DN. Meta-analysis data and intergroup comparisons indicated that PF slowed the index of mesangial expansion and tubulointerstitial injury, 24-h urinary protein excretion rate, expression of anti-inflammatory mediators (mRNA of MCP-1, TNF-α, iNOS, and IL-1 ß), and expression of immune downstream factors (P-IRAK1, TIRF, P-IRF3, MyD88, and NF-κBp-p65). Furthermore, modeling methods, animal species, treatment duration, thickness of tissue sections during the experiment, and experimental procedures were subjected to subgroup analyses. CONCLUSION: The present study demonstrated that the reno-protective effects of PF were associated with its inhibition on macrophage infiltration, reduction of inflammatory mediators, and immunomodulatory effects. In conclusion, PF can effectively slow down the progression of DN and hold promise as a protective drug for the treatment of DN. Due to the low bioavailability of PF, further studies on renal histology in animals are urgently needed. We therefore recommend an active exploration of the dose and therapeutic time frame of PF in the clinic and in animals. Moreover, it is suggested to actively explore methods to improve the bioavailability of PF to expand the application of PF in the clinic.

Vascular-related biomarkers in psychosis: a systematic review and meta-analysis.

Background: While the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and sometimes sparse observations. We conducted a comprehensive meta-analysis to critically assess the alterations of vascular-related molecules in the cerebrospinal fluid (CSF) and blood of patients with psychotic disorders compared with healthy individuals. Methods: Databases were searched from inception to February 23, 2023. Meta-analyses were performed using a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effects of clinical correlates. Results: We identified 93 eligible studies with 30 biomarkers investigated in the CSF and/or blood. Among the biomarkers examined, psychotic disorders were associated with elevated CSF-to-serum albumin ratio (standardized mean difference [SMD], 0.69; 95% confidence interval [CI], 0.35-1.02); blood S100B (SMD, 0.88; 95% CI, 0.59-1.17), matrix metalloproteinase-9 (MMP-9; SMD, 0.66; 95% CI, 0.46-0.86), and zonulin (SMD, 1.17; 95% CI, 0.04-2.30). The blood levels of S100B, MMP-9, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) were altered in patient subgroups differing in demographic and clinical characteristics. Blood S100B level was positively correlated with age and duration of illness. Substantial between-study heterogeneity was observed in most molecules. Conclusion: The alterations in certain vascular-related fluid markers in psychotic disorders suggest disturbances in normal vascular structures and functions. However, not all molecules examined displayed clear evidence of changes. While potential impacts of clinical factors, including the administered treatment, were identified, the exploration remained limited. Further studies are needed to investigate the diverse patterns of expression, and understand how these abnormalities reflect the pathophysiology of psychosis and the impact of clinical factors.

OsGA3ox genes regulate rice fertility and plant height by synthesizing diverse active GA.

Gibberellin (GA) is an important hormone, which is involved in regulating various growth and development. GA biosynthesis pathway and synthetase have been basically clarified. Gibberellin 3ß hydroxylase (GA3ox) is the key enzyme for the synthesis of various active GA. There are two GA3ox genes (OsGA3ox1 and OsGA3ox2) in rice, and their physiological functions have been preliminarily studied. However, it is not clear how they work together to synthesize active GA to regulate rice development. In this study, the knockout mutants ga3ox1 and ga3ox2 were obtained by CRISPR/Cas9 technology. The pollen fertility of ga3ox1 decreased significantly, while the plant height of ga3ox2 decreased significantly. It shows that OsGA3ox1 is necessary for normal pollen development, while OsGA3ox2 is necessary for stem and leaf elongation. Tissue expression analysis showed that OsGA3ox1 was mainly expressed in unopened flowers, while OsGA3ox2 was mainly expressed in unexpanded leaves. The GA in different tissues of wild type (WT), and two ga3ox mutants were detected. It was found that pollen fertility is most closely related to the content of GA7, and plant height is most closely related to the content of GA1. It was found that OsGA3ox1 catalyzes GA9 to GA7 in flowers, which is closely related to pollen fertility; OsGA3ox2 catalyzes the GA20 to GA1 in unexpanded leaves, thereby regulating plant height; OsGA3ox1 catalyzes the GA19 to GA20 in roots, regulating the generation of GA3. OsGA3ox1 and OsGA3ox2 respond to developmental and environmental signals, and cooperate to synthesize endogenous GA in different tissues to regulate rice development. This study provides a reference for clarifying its role in GA biosynthesis pathway and further understanding the function of OsGA3ox.

Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8.

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1ß, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Online training to improve evidence-based leadership competencies among nurse leaders in Finland and China: study protocols for two randomised feasibility trials.

INTRODUCTION: This study protocol describes two randomised feasibility trials that will evaluate the feasibility and preliminary effectiveness of an online training course to improve evidence-based leadership competences among nurse leaders working in hospitals in Finland and China. METHODS AND ANALYSIS: Two randomised, parallel-group studies will be conducted separately: one in Finland (n=140) and one in China (n=160). Nurse leaders who fulfil the eligibility criteria will be randomly allocated (1:1) to participate in either the online evidence-based leadership training or conventional online training (reading material only). The primary outcomes will be acceptance of the online course (logging into the platform) and adherence in the online course (returned course tasks and drop-out rate of the participants). The secondary outcomes will be acceptance of the study regarding recruitment, feasibility of the eligibility criteria and outcome measures and potential effectiveness of the online course on leadership skills, evidence-based knowledge, attitudes, practice, self-efficacy, self-esteem and intention to leave. In addition, the feedback will be asked after the course. ETHICS AND DISSEMINATION: Two separate trials have received ethical clearance from local ethics committees (12/2022 in Finland, E2021167 in China). Permission to conduct the study will be granted by hospital authorities. All participants will provide electronic informed consent before baseline data are collected. The trial results will be published locally, nationally and internationally in professional and peer-reviewed journals, and shared at national and international meetings and conferences. TRIAL REGISTRATION NUMBERS: NCT05244512; NCT05244499.