Mediating role of accelerated aging in the association between depression and mortality risk: findings from NHANES.

OBJECTIVE: To investigate the association between depression, accelerated biological aging, and mortality risk, and to assess whether accelerated aging mediates the relationship between major depression and mortality risk. METHODS: A prospective cohort of 12,761 participants aged 20 years or older from the 2005-2010 cycle of the National Health and Nutrition Examination Survey (NHANES) was analyzed. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores of ≥ 10 indicating major depression. Accelerated biological aging was measured using phenotypic age acceleration (PhenoAgeAccel). Multivariable linear regression models and subgroup analyses were used to examine the association between depression and accelerated aging, while weighted multivariable Cox proportional hazards regression models and subgroup analyses assessed the impact of major depression on mortality risk. Mediation analysis was performed to assess whether PhenoAgeAccel mediated the relationship between major depression and mortality outcomes. RESULTS: Among the 12,761 adults, the weighted mean age was 46.6 years, with 48.8% being male, and 6.9% experiencing major depression. The results showed a positive association between major depression and PhenoAgeAccel (ß: 0.61, 95% CI: 0.06-1.16). Over a median follow-up duration of 11.3 years (interquartile range: 9.9-13.1), major depression was associated with increased all-cause mortality (HR: 1.35, 95% CI: 1.13-1.62) and cardiovascular mortality (HR: 1.73, 95% CI: 1.18-2.54). However, the relationship with cancer mortality was not statistically significant after full adjustment for confounding factors. The mediation analysis further revealed that PhenoAgeAccel accounted for 10.32% and 5.12% of the associations between major depression and all-cause mortality, and cardiovascular mortality, respectively. CONCLUSION: Depression is associated with accelerated aging and contributes to increased all-cause and cardiovascular mortality. Accelerated aging partially mediates the association between major depression and mortality risk. Our findings highlight the urgent need to incorporate mental health care into public health strategies to delay population aging and reduce mortality risk.

Using gold-based nanomaterials for fighting pathogenic bacteria: from detection to therapy.

Owing to the unique quantum size effect and surface effect, gold-based nanomaterials (GNMs) are promising for pathogen detection and broad-spectrum antimicrobial activity. This review summarizes recent research on GNMs as sensors for detecting pathogens and as tools for their elimination. Firstly, the need for pathogen detection is briefly introduced with an overview of the physicochemical properties of gold nanomaterials. And then strategies for the application of GNMs in pathogen detection are discussed. Colorimetric, fluorescence, surface-enhanced Raman scattering (SERS) techniques, dark-field microscopy detection and electrochemical methods can enable efficient, sensitive, and specific pathogen detection. The third section describes the antimicrobial applications of GNMs. They can be used for antimicrobial agent delivery and photothermal conversion and can act synergistically with photosensitizers to achieve the precise killing of pathogens. In addition, GNMs are promising for integrated pathogen detection and treatment; for example, combinations of colorimetric or SERS detection with photothermal sterilization have been demonstrated. Finally, future outlooks for the applications of GNMs in pathogen detection and treatment are summarized.

KA-mediated excitotoxicity induces neuronal ferroptosis through activation of ferritinophagy.

OBJECTIVES: This study aims to elucidate the role of Fe2+ overload in kainic acid (KA)-induced excitotoxicity, investigate the involvement of ferritinophagy selective cargo receptor NCOA4 in the pathogenesis of excitotoxicity. METHODS: Western blotting was used to detect the expression of FTH1, NCOA4, Lamp2, TfR, FPN, and DMT1 after KA stereotaxic injection into the unilateral striatum of mice. Colocalization of Fe2+ with lysosomes in KA-treated primary cortical neurons was observed by using confocal microscopy. Desferrioxamine (DFO) was added to chelate free iron, a CCK8 kit was used to measure cell viability, and the Fe2+ levels were detected by FerroOrange. BODIPY C11 was used to determine intracellular lipid reactive oxygen species (ROS) levels, and the mRNA levels of PTGS2, a biomarker of ferroptosis, were measured by fluorescent quantitative PCR. 3-Methyladenine (3-MA) was employed to inhibit KA-induced activation of autophagy, and changes in ferritinophagy-related protein expression and the indicated biomarkers of ferroptosis were detected. Endogenous NCOA4 was knocked down by lentivirus transfection, and cell viability and intracellular Fe2+ levels were observed after KA treatment. RESULTS: Western blot results showed that the expression of NCOA4, DMT1, and Lamp2 was significantly upregulated, while FTH1 was downregulated, but there were no significant changes in TfR and FPN. The fluorescence results indicated that KA enhanced the colocalization of free Fe2+ with lysosomes in neurons. DFO intervention could effectively rescue cell damage, reduce intracellular lipid peroxidation, and decrease the increased transcript levels of PTGS2 caused by KA. Pretreatment with 3-MA effectively reversed KA-induced ferritinophagy and ferroptosis. Endogenous interference with NCOA4 significantly improved cell viability and reduced intracellular free Fe2+ levels in KA-treated cells. CONCLUSION: KA-induced excitotoxicity activates ferritinophagy, and targeting ferritinophagy effectively inhibits downstream ferroptosis. Interference with NCOA4 effectively attenuates KA-induced neuronal damage. This study provides a potential therapeutic target for excitotoxicity related disease conditions.

Psychometric validation of the Chinese version of the dry eye-related quality-of-life score questionnaire.

AIM: To psychometrically validate the Chinese version of the dry eye-related quality-of-life score questionnaire (DEQS-CHN) among Chinese patients with dry eye. METHODS: This study involved 231 participants, including 191 with dry eye disease (DED) comprising the dry eye disease group, and 40 healthy participants forming the control group. Participants were required to complete the DEQS-CHN, and Chinese dry eye questionnaire and undergo clinical tests including the fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I test. To assess the internal consistency and retest reliability, Cronbach's α and the intraclass correlation coefficient (ICC) were employed. Content validity was assessed by item-level content validity index (ICV) and an average scale-level content validity index (S-CVI/Ave). Construct validity was assessed by confirmatory factor analysis. The concurrent validity was assessed by calculating correlations between DEQS-CHN and Chinese dry eye questionnaire. Discriminative validity was evaluated through non-parametric tests, with receiver operating characteristic (ROC) curve serving as conclusive indicators of the questionnaire's distinguishing capability. RESULTS: The Cronbach's α coefficients for frequency and degree of ocular symptoms, impact on daily life, and summary score were 0.736, 0.704, 0.811, 0.818, 0.861, and 0.860, respectively, and the ICC were 0.611, 0.677, 0.715, 0.769, 0.711, and 0.779, respectively. All I-CVI scores ranged from 0.833 to 1.000, with an S-CVI/Ave of 0.956. Confirmatory factor analysis results exhibited a well-fitting model consistent with the original questionnaire [χ 2/df=2.653, incremental fit index (IFI)=0.924, comparative fit index (CFI)=0.924, Tucker-Lewis index (TLI)=0.909, and root mean square error of approximation (RMSEA)=0.065]. There was a moderate positive correlation between the DEQS-CHN and the Chinese dry eye questionnaire (r 2=0.588). The dry eye group demonstrated significantly higher scores compared to the control group, and the area under the curve (AUC) value was 0.8092. CONCLUSION: The DEQS-CHN has been demonstrated as a valid and reliable instrument for assessing the impact of dry eye disease on the quality of life among Chinese individuals with DED.

Treatment of acute dacryocystitis by translacrimal canalicular drainage and D-silicone intubation.

AIM: To demonstrate the outcomes of translacrimal canalicular drainage using a lacrimal probe and intranasal drainage by D-silicone intubation for acute dacryocystitis (AD). METHODS: This retrospective study included 23 patients with AD and had undergone abscess decompression with the use of lacrimal probe and intranasal drainage by D-silicone intubation between January 2019 and December 2022. Patients received abscess decompression and systemic antibiotic-corticosteroid from the time of diagnosis. D-silicone tube was inserted within 10d after diagnosis and removed 3-6mo after intubation. The procedure and outcomes of this method were evaluated. RESULTS: All patients showed improvement of signs and symptoms of AD within 72h. No intraoperative and postoperative complications were observed. No recurrence of lacrimal sac abscesses occurred after D-silicone tube removed. CONCLUSION: Lacrimal probe and D-silicone intubation appear to be a feasible, minimally invasive, safe, and effective method, which could be a reasonable choice in the treatment of AD.

Evaluating the Efficacy of Wrist-Ankle Acupuncture Combined With Patient-Controlled Intravenous Analgesia for Managing Post Uvulopalatopharyngoplasty.

OBJECTIVE: The aim of this study is to investigate the impact of combining wrist-ankle acupuncture with patient-controlled intravenous analgesia (PCIA) on active pain and food intake in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) after undergoing uvulopalatopharyngoplasty (UPPP). METHODS: Sixty patients with OSAHS who underwent UPPP at our hospital's Department of Otorhinolaryngology from January 2020 to October 2023 were selected and randomly divided into 2 groups of 30 each: an observation group and a control group. The control group received general anesthesia administered by an anesthesiologist and used a PCIA pump. In addition to this treatment, the observation group received the combined intervention of wrist-ankle acupuncture. Active pain levels were monitored at 0, 6, 12, 24, 36, and 48 hours after UPPP, and food intake was observed at 24, 36, and 48 hours postoperation. The results were compared and recorded for both groups. RESULTS: The analgesic effect on active pain in the observation group was significantly greater than in the control group at 6, 12, 24, 36, and 48 hours postoperation, and the differences were statistically significant (P<0.05). In addition, when comparing food intake scores at 24, 36, and 48 hours postoperation, the observation group had significantly higher food intake than the control group, and the differences were statistically significant (P<0.05). CONCLUSIONS: The combined intervention of wrist-ankle acupuncture and PCIA provides effective pain relief for OSAHS patients after UPPP, enhances their food intake, improves their quality of life, and supports early recovery.

Protein phosphatase 4 maintains the survival of primordial follicles by regulating autophagy in oocytes.

In mammalian ovary, the primordial follicle pool serves as the source of developing follicles and fertilizable ova. To maintain the normal length of female reproductive life, the primordial follicles must have adequate number and be kept in a quiescent state before menopause. However, the molecular mechanisms underlying primordial follicle survival are poorly understood. Here, we provide genetic evidence showing that lacking protein phosphatase 4 (PPP4) in oocytes, a member of PP2A-like subfamily, results in infertility in female mice. A large quantity of primordial follicles has been depleted around the primordial follicle pool formation phase and the ovarian reserve is exhausted at about 7 months old. Further investigation demonstrates that depletion of PPP4 causes the abnormal activation of mTOR, which suppresses autophagy in primordial follicle oocytes. The abnormal primordial follicle oocytes are eventually erased by pregranulosa cells in the manner of lysosome invading. These results show that autophagy prevents primordial follicles over loss and PPP4-mTOR pathway governs autophagy during the primordial follicle formation and dormant period.

Psychometric evaluation of the Chinese version of the Academic Resilience Scale-30 (C-ARS-30) in college students.

Background: Amidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored. Objective: This study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education. Methods: A convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach's alpha and test-retest reliability. Results: The C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale's 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach's α = 0.930) and test-retest reliability (0.794, p < 0.01). Conclusion: The C-ARS-30 is a reliable and valid instrument for assessing academic resilience among Chinese college students, offering a valuable tool for educational and psychological evaluations.

Visible-Light Mediated Nickel-Catalyzed Asymmetric Difunctionalizations of Alkenes.

Difunctionalizations of alkenes represent one of the most straightforward protocols to build molecular complexity due to the simultaneous construction of two vicinal bonds cross π-bond of alkenes. It is extremely attractive yet challenging to control the stereochemistry outcome of this event. Over the past years, visible-light and Ni-catalyzed asymmetric difunctionalizations of alkenes provide an environmental benign and promising solution for the construction of saturated carbon centers with the control of regio- and enantioselectivity. In this Concept, the initiative and progress of regio- and enantioselective difunctionalizations of alkenes enabled by visible-light and nickel catalysis has been summarized. Moreover, further efforts and directions for the development of visible-light mediated Ni-catalyzed asymmetric difunctionalizations of alkenes has been discussed.

[Spatial and Temporal Scale Effects of Landscape Pattern on Riverine Nitrogen and Phosphorus Nutrients in the Qingshan Lake Watershed].

The influences of landscape pattern on water quality are dependent on spatial-temporal scales. However, the effects of landscape composition, landscape configuration, and landscape slope metrics on seasonal water quality at different spatial scales remain unclear. Based on the total nitrogen, total phosphorus, nitrate-N, and ammonium-N data from 26 sampling sites in the Qingshan Lake watershed, this study coupled landscape pattern analysis, redundancy analysis, and partial redundancy analysis to quantify the spatiotemporal scale effects of landscape pattern on riverine nitrogen （N） and phosphorus （P） concentrations. The results showed that： ① The explanatory ability of landscape pattern at the sub-watershed scale on riverine N and P concentrations was 6.8%-8.4% higher than that at the buffer scale, and this effect was more obvious in the dry season. ② At the sub-watershed scale, the percentage of forestland and the interspersion and juxtaposition degree of residential land had a greater influence on riverine N and P concentrations. At the buffer scale, the slope of farmland and residential land and the aggregation degree of forestland patches were the key factors affecting riverine N and P concentrations. ③ The contribution rate of landscape configuration to riverine N and P concentration variations （20.1%-36.5%） was the highest. The sensitivity of the effect of landscape configuration on riverine N and P concentrations to seasonal changes was the highest, and the effect of landscape slope on riverine N and P concentrations had the highest sensitivity to spatial scale changes. Therefore, landscape pattern-regulated non-point source pollution should be considered from a multi-scale perspective. These results can provide scientific basis for the formulation of landscape pattern optimization measures aiming at non-point source pollution control.

Association of visceral adiposity index with phenotypic age acceleration: insight from NHANES 1999-2010.

BACKGROUND: Obesity correlates with accelerated aging. This study aims to investigate the association between the visceral adiposity index (VAI) and accelerated aging. METHODS: Biological aging was evaluated by phenotypic age acceleration (PhenoAgeAccel). Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2010, we employed weighted multivariable logistic regression models, along with subgroup analysis, to examine the association between VAI and PhenoAgeAccel. Moreover, smooth curve fitting was utilized to identify potential nonlinear association, complemented by a two-piece linear regression model to investigate threshold effects. RESULTS: Of the included 11,340 participants aged 20 years and older, the mean (95% CI) age was 46.569 (45.946, 47.191) years, and 49.189% were male. The mean (95% CI) VAI for all participants was 2.176 (2.114, 2.238), and the mean (95% CI) PhenoAgeAccel was -6.306 (-6.618, -5.994) years. In the fully adjusted model, each incremental unit increase of VAI was associated with a 0.312-year increase in PhenoAgeAccel (ß = 0.312, 95% CI: 0.217, 0.408). This positive association was more statistically significant among individuals with cancer. Furthermore, a segmented association was observed between VAI and PhenoAgeAccel, with a turning point identified at 10.543. Below this threshold, VAI exhibited a positive correlation with PhenoAgeAccel (ß = 0.617, 95% CI: 0.499, 0.735), while beyond it, the association became nonsignificant. CONCLUSION: This study demonstrated a positive association between VAI and accelerated aging within a nationally representative population. The findings suggest that controlling adiposity may exert anti-aging effects and help prevent aging-related diseases.

Comparative transcriptome analysis provides comprehensive insight into the molecular mechanisms of heat adaption in Plutella xylostella.

Plutella xylostella is one of the most destructive pests for cruciferous vegetables, and is adaptability to different environmental stressors. However, we still know little about the molecular mechanisms of how P. xylostella adapt to thermal stress. Here, the comparative transcriptome analysis was conducted from the samples of control (27 °C, CK) and heat treatment (40 °C, 40 T) P. xylostella. The results showed 1253 genes were differentially expressed, with 624 and 629 genes up- and down-regulated respectively. The annotation analysis demonstrated that "Energy production and conversion", "Protein processing in endoplasmic reticulum", "Peroxisome" and "Tyrosine metabolism" pathways were significantly enriched. Additionally, we found the expression levels of heat shock protein genes (Hsps), cuticle related genes and mitochondrial genes were significantly up-regulated in 40 T insects, suggesting their vital roles in improving adaption to heat stress. Importantly, the SOD activity and MDA content of P. xylostella were both identified to be increased under high temperature stress, indicating the elevated antioxidant reactions might be involved in response to heat stress. In conclusion, the present study offered us an overview of gene expression changes after 40 °C treatments, and found some critical pathways and genes of P. xylostella might play the critical roles in resisting heat stress.

AcornHRD: an HRD algorithm highly associated with anthracycline-based neoadjuvant chemotherapy in breast cancer in China.

PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.

Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity.

Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species. Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.

[Clinical study of Bushen Culuan Formula in treatment of ovulatory disorder infertility caused by hyperprolactinemia].

This paper aims to study the therapeutic effect and safety of Bushen Culuan Formula in the treatment of patients with infertility caused by hyperprolactinemia. Sixty patients with infertility caused by hyperprolactinemia of kidney deficiency and blood stasis were divided into the treatment group(Bushen Culuan Formula + Bromocriptine Mesylate Tablets placebo) and the control group(Bromocriptine Mesylate Tablets + Bushen Culuan Formula placebo), and ovulation rate, pregnancy rate, serum sex hormones, basal body temperature(BBT), and traditional Chinese medicine(TCM) symptom scores were observed. The results showed the clinical effective rate was 90.00% in the treatment group and 80.00% in the control group. The treatment group was able to significantly reduce the PRL level and increase the pregnancy rate, and it was superior to the control group in increasing the BBT biphasic ratio, improving the TCM symptom scores, and enhancing the ovulation rate. The results show that Bushen Culuan Formula is safe and reliable in treating ovulatory disorder infertility caused by hyperprolactinemia, with remarkable effects.

[Examples of Professor MA Kun's treatment of infertility caused by uterine fibroids using method of tonifying kidney and activating blood].

Uterine fibroids are a prevalent factor that impacts fertility in women of reproductive age. This study discusses the theoretical foundation and formula principles of Professor MA Kun's clinical treatment for infertility caused by uterine fibroids. The kidney stores essence and is responsible for reproduction, while blood serves as a vital material basis for women's physiological functions. Kidney deficiency is the fundamental pathogenesis of infertility, and imbalances in kidney Qi and essence or deficiencies in kidney Yin and Yang can result in blood stasis. Blood stasis plays a significant role throughout this condition by impeding the flow of blood, which is crucial for nourishing Qi. Therefore, both kidney deficiency and blood stasis are key factors contributing to infertility caused by uterine fibroids. Professor MA Kun treats infertility caused by uterine fibroids using an approach that involves tonifying the kidneys and activating blood circulation based on changes in Qi and blood during the menstrual cycle as well as follicular growth processes. By identifying stage-specific evidence, appropriate treatments can be applied accordingly. During menstruation when the uterus opens and menstrual blood flows out, promoting follicular development through nourishing kidney Yin and activating blood circulation becomes essential. In later stages of menstruation, additional measures are taken to remove blood stasis, alleviate symptoms, disperse knots, attack pathogens while simultaneously replenishing vital energy. During intermenstrual periods when Yin holds greater importance than Yang, tonifying the kidneys and activating blood circulation helps facilitate smooth discharge of eggs by promoting transformation between Yin and Yang energies. Premenstrual period to warm kidney Yang to promote pregnant egg implantation, and at the same time to dredge the liver and regulate Qi, Qi elimination stagnation, complementary in the line, with the symptoms of additional subtractions. Clinical effect is remarkable, for the reference of colleagues.

[Study on mechanism of regulation of sex hormones in treatment of hyperprolactinemia-induced ovulatory disorder infertility with Bushen Culuan Formula].

Transcriptomics was used to investigate the mechanism of action of Bushen Culuan Formula in the treatment of infertility caused by hyperprolactinemia(HPRL), and animal experiments were carried out to verify the results. After establishing an animal model of HPRL-induced infertility, the mice were divided into normal group, model group, Bushen Culuan Formula groups with high-, medium-, and low-doses, and bromocriptine group, and they were observed in terms of the estrous cycle, gonadal index, serum sex hormones, morphology of ovary and mammary gland, follicle count, and fertility. The results showed that the Bushen Culuan Formula could effectively restore the estrous cycle, down-regulate the levels of prolactin(PRL), follicle-stimulating hormone(FSH), and luteinizing hormone(LH), up-regulate the level of estradiol(E_2), increase the number of primordial follicles and sinus follicles, and improve the ovulation rate and fertility of mice. Through RNA sequencing combined with biosignature analysis, Bushen Culuan Formula may regulate the metabolism of lipids, antioxidant enzymes, and other substances in the cells of the ovary and pituitary gland through the signaling pathways of cAMP-PKA, Kiss-1/GPR54, and Hippo and exert therapeutic effects. The results of animal experiments showed that Bushen Culuan Formula could up-regulate serum dopamine(DA) level and pituitary DRD2 expression, down-regulate hypothalamus and ovary cAMP levels, as well as protein expressions of the pituitary gland and ovary PKA, CREB, and p-CREB, and treat HPRL-induced infertility by regulating the cAMP-PKA signaling pathway.

[Bushen Culuan Formula in treatment of infertility caused by polycystic ovary syndrome].

This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.

Multidirectional Intervention of Chinese Herbal Medicine in the Prevention and Treatment of Atherosclerosis: From Endothelial Protection to Immunomodulation.

Atherosclerosis is a significant risk factor for developing cardiovascular disease and a leading cause of death worldwide. The occurrence of atherosclerosis is closely related to factors such as endothelial injury, lipid deposition, immunity, and inflammation. Conventional statins, currently used in atherosclerosis treatment, have numerous adverse side effects that limit their clinical utility, prompting the urgent need to identify safer and more effective therapeutic alternatives. Growing evidence indicates the significant potential of Chinese herbs in atherosclerosis treatment. Herbal monomer components, such as natural flavonoid compounds extracted from herbs like Coptis chinensis and Panax notoginseng, have been utilized for their lipid-lowering and inflammation-inhibiting effects in atherosclerosis treatment. These herbs can be used as single components in treating diseases and with other Chinese medicines to form herbal combinations. This approach targets the disease mechanism in multiple ways, enhancing the therapeutic effects. Thus, this review examines the roles of Chinese herbal medicine monomers and Chinese herbal compounds in inhibiting atherosclerosis, including regulating lipids, improving endothelial function, reducing oxidative stress, regulating inflammation and the immune response, and apoptosis. By highlighting these roles, our study offers new perspectives on atherosclerosis treatment with Chinese herbs and is anticipated to contribute to advancements in related research fields.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.