Pharmacokinetics and related gender difference studies of four active components of Codonopsis Pilosula by LC-MS/MS determination.

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis pilosula (C. pilosula), commonly known as Dangshen in Chinese, had been used to regulate the immune, digestive, and circulatory systems of human. The reported pharmacokinetic studies on C. pilosula are mainly limited to in vivo profile studies of a single component. It has not been detected simultaneously the in vivo pharmacokinetic profiles of multiple active components as well as related gender difference after oral dosing of the extraction of C. pilosula. AIM OF THE STUDY: This study aims to reveal the pharmacokinetic characteristics of the four main active components of C. pilosula after oral dosing of its extraction in rats, and to explain the gender differences in absorption and metabolism. MATERIALS AND METHODS: The plasma pharmacokinetic characteristics of four main active components of C. pilosula was explored using the established LC-MS/MS method after oral dosing of the extraction of C. pilosula in male and female rats. In vitro intestinal pouch permeability and liver microsome metabolic stability were also observed to classify the possible mechanism of gender difference existed in the pharmacokinetic profiles of the four active components in rats. RESULTS: Four effective components were absorbed quickly in rats after oral administration of alcoholic extract of C. pilosula (1.36 g/mL, equivalent to 2 g/mL as crude drug), and their exposure order was as follows: Atractylenolide III > Lobetyolin > Tangshenoside I > Syringin. The exposure (AUC) and peak concentration (Cmax) of Atractylenolide III in female rats were much higher than those in male rats, indicating a significant gender difference in pharmacokinetics of Atractylenolide III between female and male animals. With the help of the rat model of intestinal sac in vitro, it was found that Lobetyolin was a hypertonic compound, and both Tangshenoside I and Syringin were compounds with medium permeabiltiy. Notably, the Papp of Atractylenolide III was 3.3×10-6 cm/s in male rat intestinal sac assay, while that was 10×10-6 cm/s in female rat intestinal sac model, showing a significant gender difference in intestinal permeability (P<0.05). After the addition of NADPH, the four compounds were reduced in a time-dependent manner, suggesting that CYP450s could catalyze their metabolism. After incubation, the remaining content of Atractylenolide III in the liver microsomes of male and female rats was 27% and 57%, respectively, suggesting slower metabolic rate of in female rat liver microsomes. CONCLUSION: A simple, efficient and reliable LC-MS/MS method for the simultaneous determination of four active index components of C. pilosula, Lobetyolin, Tangshenoside I, Atractylenolide III and Syringin, in rat plasma was established and verified. This method was successfully applied in the pharmacokinetic study after single oral administration of the alcoholic extract of C. pilosula in rats. Gender difference was observed in the pharmacokinetic profile of Atractylenolide III in rats. Intestinal absorption and liver metabolism might be two key factors that resulted in the gender difference in exposure and pharmacokinetics of Atractylenolide III in rats. This study provides supportive data for clinical rational application of C. pilosula in individualized medication therapy.

Retinal nerve fiber layer defects and chronic kidney disease: the Kailuan Eye Study.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials.

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Synthesis of Silver(I) Complexes through In Situ Reactions of dppeda with dmp in the Presence of Silver Halides for Photocatalysis.

Due to the unique photosensitivity of silver compounds, they exhibit good photocatalytic activity as photocatalysts in the degradation of water pollutants. However, silver compounds have poor cycling stability and are prone to decomposition and reaction under light to form metallic silver, which greatly limits their practical application. Herein, a (2-(2-(diphenylphosphaneyl)ethyl)-9-methyl-1.10-phenanthroline (PSNNP)) pincer ligand was designed for stabilizing the central metal. The in situ-formed PSNNP ligand could be readily generated in one pot with the participation of silver halides. The reaction of silver halides with dppeda (N,N,N',N'-tetra(diphenylphosphanylmethyl)ethylene diamine) in the presence of dmp (2,9-dimethyl-1,10-phenanthroline) in acetonitrile afforded complexes Ag2X2 (PSNNP)2 (complexes 1, 2) (X = Cl, Br). Single-crystal X-ray diffraction shows that the tridentate coordination of the pincer ligand provides strong binding with metal centers and leads to high stability of the pincer metal unit. The removal rate of rhodamine B (RhB) by complexes 1 and 2 can reach up to 100%, demonstrating an excellent photocatalytic degradation performance for organic dyes. The important effect of PSNNP ligands on photocatalytic properties after coordination with central metals was studied through experiments and discrete Fourier transform (DFT) calculations. The photocatalytic reaction mechanism of complexes 1 and 2 was also studied. This result provides an effective pathway for the first synthesis of PSNNP and interesting insights into photocatalytic degradation chemistry.

Mechanism of action of Taohong Siwu decoction in the alleviation of primary dysmenorrhea.

Background: As one of the most common gynecological disorders, PD significantly impacts the quality of life for women. TSD, a well-known traditional Chinese medical prescription, has gained popularity for its use in treating gynecological cold coagulation and blood stasis syndromes such as PD. However, the lack of comprehensive data hinders our understanding of its molecular mechanism. Purpose: The objective of the present study is to investigate the therapeutic effects of TSD on PD and elucidate its plausible mechanism. Methods: HPLC was employed to confirm the presence of the principal metabolites of TSD. The rat model of PD was induced by OT exposure following IWM and EB pretreatment, and subsequently treated with TSD via gastric gavage. The effects and potential mechanisms of TSD on PD rats were explored, encompassing general behavior, morphological alterations in the uterus and ovaries, biochemical indicators in the uterus and serum, and levels of proteins related to the PI3K/AKT signaling pathway. Results: Gallic acid, hydroxysafflower yellow A, albiflorin, paeoniflorin, and ferulic acid were determined to be the primary active metabolites of TSD. The pharmacological studies yielded results indicating the successful establishment of the PD model in rats. Additionally, TSD demonstrated its ability to protect PD rats by ameliorating general behavior, mitigating pathological damage to uterine and ovarian tissues, and modulating the expression levels of correlated factors (PGE2, PGF2α, Ca2+, TXB2, IL-6, TNF-α, NO, and COX-2) as well as p-PI3K/PI3K and p-AKT/AKT proteins. Conclusion: TSD exhibited protective effects against PD in rats through its interaction with multiple targets including P13K/AKT signaling pathway, indicating that TSD holds therapeutic potential for PD treatment and providing evidence supporting the rational utilization of TSD.

(±)-Involucrasin D, a pair of enantiomeric bisflavonoid from the roots of Shuteria involucrata and its anti-inflammatory activity.

An undescribed bisflavonoid, named involucrasin D (1), along with two known flavonoids, 2(S)7,3',5'-trihydroxydihydroflavone (2) and sigmone (3) were isolated from the roots of Shuteria involucrata. A further chiral separation of 1 to yielded a pair of enantiomers (+)-1 and (-)-1. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Among them, bisflavonoid 1 and its enantiomers displayed remarkable anti-inflammatory effects by inhibiting the production of TNF-α and IL-6 in a dose-dependent manner.

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

[This corrects the article DOI: 10.3389/fpsyt.2024.1354999.].

The effects of ambient temperature and feeding regimens on cecum bacteria composition and circadian rhythm in growing rabbits.

Seasonal environmental shifts and improper eating habits are the important causes of diarrhea in children and growing animals. Whether adjusting feeding time at varying temperatures can modify cecal bacterial structure and improve diarrhea remains unknown. Three batches growing rabbits with two groups per batch were raised under different feeding regimens (fed at daytime vs. nighttime) in spring, summer and winter separately, and contents were collected at six time points in 1 day and used 16S rRNA sequencing to investigate the effects of feeding regimens and season on the composition and circadian rhythms of cecum bacteria. Randomized forest regression screened 12 genera that were significantly associated with seasonal ambient temperature changes. Nighttime feeding reduced the abundance of the conditionally pathogenic bacteria Desulfovibrio and Alistipes in summer and Campylobacter in winter. And also increases the circadian rhythmic Amplicon Sequence Variants in the cecum, enhancing the rhythm of bacterial metabolic activity. This rhythmic metabolic profile of cecum bacteria may be conducive to the digestion and absorption of nutrients in the host cecum. In addition, this study has identified 9 genera that were affected by the combination of seasons and feeding time. In general, we found that seasons and feeding time and their combinations affect cecum composition and circadian rhythms, and that daytime feeding during summer and winter disrupts the balance of cecum bacteria of growing rabbits, which may adversely affect cecum health and induce diarrhea risk.

Quality assurance of postharvest grapes against Botrytis cinerea by terbinafine.

Worldwide, fruit is an indispensable treasure house of nutrition for human beings, occupying a vital position of human diet. Postharvest fruit storage requires efficient antifungal agents to control Botrytis cinerea, which is a vital postharvest disease affecting fruit and leading to enormous losses. However, with the enormous abuse of existing antifungal drugs, the problem of drug-resistant fungi is imminent, making the controlling diseases caused by pathogenic fungi even more challenging. Drug repurposing is an efficient alternative method, we evaluated a well-known antifungal chemical, terbinafine, against the agricultural pathogen, B. cinerea in vitro, as a result, terbinafine showed strong antifungal activity. Furthermore, the in vivo antifungal activity of terbinafine was evaluated, the results showed that terbinafine could reduce the decay area on grapes. Terbinafine could disrupt the cell membrane integrity, increase cell membrane permeability, and eventual cell death of B. cinerea. In addition, terbinafine reduced decay incidence, and weight loss and maintained the soluble solids, titratable acidity, ascorbic acid, total phenolic, and malondialdehyde content during the storage period of grapes. Overall, terbinafine could be an antifungal preservative for postharvest table grapes fresh-keeping.

Cu-based catalysts with the co-existence of single atoms and nanoparticles for basic electrocatalytic oxygen reduction reaction.

Developing efficient and stable oxygen reduction reaction (ORR) catalysts to replace the precious Pt/C is very important for the industrial application of proton-exchange membrane fuel cells. Herein, using bismuth-based metal-organic frameworks as the substrate to disperse copper ions, we prepared a catalyst containing both Cu single atoms and Cu nanoparticles (CuSACuNP/BiCN) by a pyrolysis method. In 0.1 M KOH electrolyte, the electrocatalytic ORR performance of CuSACuNP/BiCN was superior to that of commercial Pt/C. With a hierarchical porous architecture, CuSACuNP/BiCN displayed a half-wave potential of 0.86 V vs. RHE and a diffusion-limiting current density of 5.82 mA cm-2 with a four-electron transfer process. In addition, it was stable during a 12-hour durability test. This study provides guidance for the synthesis of advanced Cu-based nano-single-atom catalytic materials for ORR applications.

Ormosianines A-P, Structurally Diverse Quinolizidine Alkaloids with AChE Inhibitory Effects from Ormosia yunnanensis.

Sixteen new quinolizidine alkaloids (QAs), named ormosianines A-P (1-16), and 18 known congeners (17-34) were isolated from the stems and leaves of Ormosia yunnanensis. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A (1) and B (2) are the first examples of cytisine and Ormosia-type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia-type QAs, including 1, 16, 24, and 27-29, are good AChE inhibitors. Ormosianine A (1) exhibited more potent AChE inhibitory activity with an IC50 value of 1.55 µM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480.

The relationship between childhood traumatic experience and suicidal tendency in non-suicidal self-injury behavior patients.

BACKGROUND: Individuals with non-suicidal self-injury (NSSI) behavior are usually prone to repeated, intentional, direct harm to their own bodies that is not allowed by society without suicidal ideation. Under this behavior guidance, childhood traumatic experience may easily cause a series of psychological comorbidity symptoms, such as anxiety and depression, finally leading to a suicidal tendency. METHODS: A total of 311 adolescent NSSI behavioral patients were recruited at the Ningbo Kangning hospital, Zhejiang Province according to the DSM-5 diagnostic criteria. Demographic data, childhood abuse and neglect, internet addiction, self-esteem, anxiety, and suicidal tendency were evaluated. A structural equation model with a path induction mechanism was constructed to evaluate the relationship between distal and proximal factors related to suicidal tendencies due to childhood traumatic experiences in NSSI behavioral individuals. RESULTS: Among the 311 subjects included in the survey, 250 (80.39%) suffered traumatic experiences, such as emotional abuse/physical abuse/sexual abuse/emotional neglect or physical neglect in their childhood, 303 (97.43%) had suicidal ideation, 271 (87.14%) showed the total score of self-esteem, 148 (47.59%) had different degrees of Internet addiction tendency, and 286 (91.96%) showed obvious anxiety. The established path model fit well (GFI = 0.996, RMSEA = 0.03), and the model showed that self-esteem, anxiety, and childhood traumatic experience had standardized coefficients of -0.235 (z = -4.742, p < 0.01), 0.322 (z = 6.296, p < 0.01), 0.205 (z = 4.047, p < 0.01), respectively, with suicidal ideation path, suggesting that self-esteem, Internet addiction, and anxiety showed significant mediating effects in the process of childhood traumatic experience affecting suicidal ideation. CONCLUSION: In the context of childhood traumatic experience, it is often accompanied by a series of regulatory behaviors such as Internet addiction, self-esteem, and so on, which finally leads to anxiety, mental symptoms, and even suicidal tendencies. The results provide effective support for the structural equation modeling to evaluate the multi-level influence of NSSI behavior individuals and emphasize that childhood familial factors may lead to psychiatric comorbidity symptoms and suicidal behavior.

Analysis of risk and protective factors associated with retinal nerve fiber layer defect in a Chinese adult population.

AIM: To investigate the risk and protective factors associated with the retinal nerve fiber layer defect (RNFLD) in a Chinese adult population. METHODS: This study was a cross-sectional population-based investigation including employees and retirees of a coal mining company in Kailuan City, Hebei Province. All the study participants underwent a comprehensive systemic and ophthalmic examination. RNFLD was diagnosed on fundus photographs. Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD. RESULTS: The community-based study included 14 440 participants. There were 10 473 participants in our study, including 7120 males (68.0%) and 3353 females (32.0%). The age range was 45-108y, averaging 59.56±8.66y. Totally 568 participants had RNFLD and the prevalence rate was 5.42%. A higher prevalence of RNFLD was associated with older age [P<0.001, odds ratio (OR): 1.032; 95% confidence interval (CI): 1.018-1.046], longer axial length (P=0.010, OR: 1.190; 95%CI: 1.042-1.359), hypertension (P=0.007, OR: 0.639; 95%CI: 0.460-0.887), and diabetes mellitus (P=0.019, OR: 0.684; 95%CI: 0.499-0.939). The protective factors of RNFLD were visual acuity (P=0.038, OR: 0.617; 95%CI: 0.391-0.975), and central anterior chamber depth (P=0.046, OR: 0.595; 95%CI: 0.358-0.990). CONCLUSION: In our cross-sectional community-based study, with an age range of 45-108y, RNFLD is associated with older age, longer axial length, hypertension, and diabetes mellitus. The protective factors of RNFLD are visual acuity and central anterior chamber depth. These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.

The Effect of the COVID-19 Pandemic on the Decision-making Process of Mandibular Impacted Third Molar Extraction.

Objectives: In this study, we investigated the impact of the COVID-19 pandemic on the decision-making process for impacted mandibular third molar removal and related clinical teaching. Methods: From April 21 to April 28, 2020, we distributed a self-constructed survey via the Wenjuanxing software platform to oral clinicians engaged in the extraction of mandibular third molars. Results: We received 321 valid responses. Overall, 22.4% of clinicians were temporarily not performing tooth extractions in outpatient clinics and 50.2% of clinicians were temporarily not performing impacted tooth extractions. The main reason cited was that aerosol-generating high-speed handpieces were not recommended for use during the pandemic, opting instead for the surgical handpiece with copious saline irrigation as the main method for bone removal; the hammer-and-chisel method was considered to be too traumatic and posed too high of a risk for iatrogenic injury. Conclusions: The implementation of disease control measures during the COVID-19 pandemic significantly affected clinical decision-making regarding impacted mandibular third molar extractions; the main reason cited was the contraindication of using aerosol-generating high-speed handpieces. The hammer-and-chisel method may represent a valuable surgical application under the requirements for epidemic prevention and control. We provide a new idea for the extraction of interrupted permanent molars in the context of epidemic prevention and control is provided.

MicroRNA-592 Inhibits the Growth of Ovarian Cancer Cells by Targeting ERBB3.

Objectives: Ovarian cancer is the most lethal gynecologic malignancy, and targeted therapy for different pathological types and molecular phenotypes is urgent to be studied. Studies have shown that MicroRNA-592 (miR-592) plays an important negative regulatory role in the occurrence of gastrointestinal malignancies, breast cancer, non-small cell lung cancer, and glioma, but the expression of miR-592 in ovarian cancer and the mechanism of action are still unclear. Methods: The expressions of miR-592 were examined by RT-PCR and Western Blot. Cell viability and migratory capacity were detected by CCK-8 and transwell assay. TargetScan (http://www.targetscan.org) was analyzed to predict potential targets of miR-592. Then Dual-luciferase reporter gene assay was performed to verify the targeting relationship between miR-592 and ERBB3. A mouse xenograft model was applied to confirm the effect of miR-592. Results: In our study, we found that the expression of miR-592 is reduced in epithelial ovarian cancer tissues. The exogenous expression of miR-592 inhibits the proliferation, migration, and invasion in epithelial ovarian cancer tumor cells. Furthermore, the exogenous expression of miR-592 inhibits tumor growth in the nude mouse xenograft model. Therefore, miR-592 may play a role of tumor suppressor miRNA in the occurrence and development of ovarian cancer. Further experiments demonstrated that tumor-related ERBB3 is a target gene mediated by miRNA-592. The dual-luciferase reporter system was used to identify miRNA-592 target genes; qPCR and Western Blot were used to detect the expression of ERBB3. Mechanical experiments confirmed that miRNA-592 negatively regulated ERBB3.Conclusion: Together, these findings identify a heretofore unrecognized link between miR-592 and ERBB3 and suggest that targeting on miR-592 warrants attention as a novel and potential therapeutic strategy for ovarian cancer.

Dimeric benzylisoquinoline alkaloids from Thalictrum delavayi and their biological activities.

A phytochemical investigation of the whole plants of T. delavayi led to the isolation of five new dimeric benzylisoquinoline alkaloids, thalidelavines A-E (1-5), together with six known congeners (6-11). The structures and absolute configurations of new compounds were established based on analyses of spectroscopic data, ECD calculations, and single crystal X-ray crystallography. Thalidelavines A-E (1-5) were structurally complex bisbenzylisoquinoline alkaloids with various configurations. These isolated alkaloids were evaluated for their cytotoxic and immunosuppressive effects. Among them, both 9 and 10 displayed significant cytotoxicities against T98G cell lines with an IC50 value of 2.1 µM, compared with the positive CPT-11 (IC50 = 3.0 µM). In addition, 5-7 showed remarkable immunosuppressive effects. These findings not only enrich the structural diversity of bisbenzylisoquinoline alkaloids, but also provide potential candidates for the further development of the antitumor and immunosuppressive agents.

Association of MBOAT7 rs641738 polymorphism with hepatocellular carcinoma susceptibility: A systematic review and meta-analysis.

BACKGROUND: The MBOAT7 rs641738 single-nucleotide polymorphism (SNP) has been proven to influence various liver diseases, but its association with hepatocellular carcinoma (HCC) susceptibility has been debated. To address this discrepancy, we conducted the current systematic review and meta-analysis. AIM: To perform a systematic review and meta-analysis on association of MBOAT7 SNP and HCC susceptibility. METHODS: We performed a systematic review in PubMed, Web of Science, Scopus, and EMBASE; applied specific inclusion and exclusion criteria; and extracted the data. Meta-analysis was conducted with the meta package in R. Sensitivity and subgroup analyses were also performed. This meta-analysis was registered in PROSPERO (CRD42023458046). RESULTS: Eight studies were included in the systematic review, and 12 cohorts from 6 studies were included in the meta-analysis. Our meta-analysis revealed an association between the MBOAT7 SNP and HCC susceptibility in both the dominant [odds ratio (OR): 1.14, 95% confidence interval (95%CI): 1.02-1.26, P = 0.020] and recessive (OR: 1.21, 95%CI: 1.05-1.39, P = 0.008) models. Subgroup analysis revealed that stratification of the included patients by geographical origin showed a significant association in Asia (OR: 1.20, 95%CI: 1.03-1.39). CONCLUSION: This meta-analysis underscores the contribution of the MBOAT7 rs641738 SNP to hepatocarcinogenesis, especially in Asian populations, which warrants further investigation.

The Influence of Diabetes, Hypertension, and Hyperlipidemia on the Onset of Age-Related Macular Degeneration in North China: The Kailuan Eye Study.

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion: There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.

Effect of ursodeoxycholic acid on gallstone formation after bariatric surgery: An updated meta-analysis.

OBJECTIVE: Bariatric surgery increases the risk of postoperative gallstone formation. Many studies have proposed ursodeoxycholic acid (UDCA) as a preventive agent for postoperative gallstone formation. This study aimed to investigate the effect of UDCA on gallstone formation after bariatric surgery in patients without preoperative gallstones. METHODS: PubMed, the Web of Science, the Cochrane Library, and EBSCO were searched for articles assessing the effect of UDCA on gallstone formation after bariatric surgery. The outcome was the incidence of postoperative gallstones. Odds ratios were used to assess dichotomous variables, and random-effects models were used for statistical analyses. RESULTS: A total of 18 studies including 4,827 participants met the inclusion criteria. The statistical results showed that the incidence of gallstones in the UDCA group was significantly lower than in the control group. Furthermore, the occurrence of symptomatic gallstones and cholecystectomy was significantly reduced. CONCLUSIONS: In patients without preoperative gallstones, UDCA can effectively prevent the formation of gallstones after bariatric surgery. In addition, UDCA can significantly reduce the occurrence of symptomatic gallstones and the risk of postoperative cholecystectomy. Doses of 500 to 600 mg/d can be used as a measure to prevent postoperative gallstone formation.