ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Objective:To observe the effects of Bushen Antai Mixture on nuclear transcription factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/nuclear transcription factor-κB (NF-κB) in placental tissue of recurrent spontaneous abortion (RSA) mice.Methods:The CBA/J mice (female) and DBA/2 (male), CBA/J mice (female) and BALB/c (male) were caged at a ratio of 2 : 1 to establish RSA and normal pregnant mice, respectively. The next morning, the vaginal plug was found or the sperm was seen under the microscope as the successful modeling, which was counted as the first day of pregnancy. CBA/J×BALB/c mice were set as normal group, and the RSA model pregnant mice were divided into model group, progesterone group, and Bushen Antai Mixture low-, medium-, and high-dosage groups using a random number table method, with 6 mice in each group. The normal group and the model group were given distilled water by gavage. Bushen Antai Mixture low-, medium-, and high-dosage groups were given 3.9 g/kg, 11.7 g/kg and 23.4 g/kg Bushen Antai Mixture by gavage. The progesterone group was given progesterone capsule aqueous solution 26 mg/kg by gavage for 14 consecutive days. The embryo loss rate of mice was calculated. The pathological changes of placental tissues were observed by HE staining. The expressions of Nrf2, HO-1 and NF-κB protein and mRNA in placental tissues were detected by Western blot and RT-qPCR.Results:Compared with the model group, the embryo loss rate of mice in the Bushen Antai Mixture low-, medium-, and high-dosage groups and the progesterone group significantly decreased ( P<0.05, P<0.01); the pathological morphology of placental tissue improved; the expressions of Nrf2, HO-1 protein and mRNA in placental tissue significantly increased ( P<0.05, P<0.01), and the expression of NF-κB protein and mRNA significantly decreased ( P<0.05, P<0.01). Conclusion:Bushen Antai Mixture may may treat RSA by activating the Nrf2/HO-1 pathway, inhibiting NF - κB expression, and improving oxidative stress and inflammatory response in the placental tissue of RSA pregnant mice.

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

OBJECTIVE: To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated. RESULTS: In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). CONCLUSION The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans ; China/epidemiology* ; Female ; Male ; Adult ; Middle Aged ; Prevalence ; Young Adult ; Adolescent ; Aged ; Child ; Headache Disorders/epidemiology* ; Disability-Adjusted Life Years ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over