Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

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.

Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

A pyrene-phenol-based fluorescent probe PyP which showed typical intramolecular charge transfer(ICT)and monomer-excimer activities was synthesized by using pyrene carboxaldehyde hydrazone and 4-tert-butyl-2,6-diformylphenol as the raw materials.The effects of solvents on PyP were studied,and the results showed that the color of protic polar solvents(Ethanol,N,N-dimethylformamide,methanol and H2O)were successfully identified.Based on the solvent polarity-regulated PyP monomer-excimer switching,the rapid and highly sensitive ratiometric probe,"Turn-off"and"Turn-on"multimodal probes were established for detection of trace water content in organic solvents(Dimethyl sulfoxide,N,N-dimethylformamide,ethanol and methanol),with detection limits(3σ/k)of 0.0021％,0.046％,0.062％and 0.024％.The method was successfully used to detect water content in dimethyl sulfoxide,N,N-dimethy lformamide,ethanol and methanol commercial organic solvents,with recoveries ranging from 97.2％to 108.0％.The developed method showed good accuracy and stability,and had good application prospect.

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.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C