Based on the traditional Chinese medicine(TCM) theory of "kidney-brain interaction", a two-sample Mendelian randomization(MR) analysis was conducted to investigate the causal effects of chronic kidney disease(CKD) on Alzheimer's disease(AD) and analyze the potential mechanisms of kidney-tonifying and essence-replenishing TCM to improve AD. From the perspective that CKD is closely related to the core pathogenesis of AD, namely "kidney deficiency, essence loss, and marrow reduction", genome-wide association study(GWAS) data was used, with the inverse variance weighting(IVW) method as the main approach to reveal the causal association between CKD and AD. Sensitivity analysis was conducted to evaluate the robustness of the results. To further investigate the causal effects of CKD on AD, two different AD datasets were used as outcomes, and the urinary albumin-to-creatinine ratio(UACR) data was used as the exposure for a supplementary analysis. On this basis, the modern scientific mechanism of the kidney-tonifying and essence-replenishing method for improving AD was further explored. The IVW analysis show that CKD(ieu-b-2: OR=1.084, 95%CI[1.011, 1.163], P=0.024; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.001], P=0.002) and UACR(ieu-b-2: OR=1.247, 95%CI[1.021, 1.522], P=0.031; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.003], P=0.015) both have significant causal effects on AD in different datasets, with CKD increasing the risk of AD. The sensitivity analysis further confirmed the reliability of the results. Genetic studies have shown that CKD has a significant causal effect on AD, suggesting that controlling CKD is an important intervention measure for preventing and treating AD. Therefore, further research on CKD's role in AD is crucial in clinical practice. The research enriches the theoretical implication of "kidney-brain interaction", deepens the understanding of AD' etiology, and provides further insights and directions for the prevention and treatment of AD with TCM, specifically from a kidney-based perspective.
Humans ; Alzheimer Disease/genetics* ; Renal Insufficiency, Chronic/genetics* ; Kidney/metabolism* ; Brain/physiopathology* ; Genome-Wide Association Study ; Medicine, Chinese Traditional ; Mendelian Randomization Analysis

It has been popular and challenging to undertake researches on the delay of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). As key cells for tumor initiation, cancer stem cells (CSC) play an important role in the process of resistance to EGFR-TKI. Although preliminary studies found that traditional Chinese medicine (TCM) could inhibit CSC properties and delay EGFR-TKI resistance, the specific molecular mechanism remains unclear. By summarizing the empirical syndrome treatment of EGFR-TKI resistance via TCM and combining recent researches on TCM intervention in CSC to delay EGFR-TKI resistance, this review discussed the potential molecular pathways and mechanisms of deceleration in resistance to EGFR-TKI by TCM via inhibiting CSC characteristics, in order to expand the research ideas of TCM in combination with targeted therapy.
Humans ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Medicine, Chinese Traditional ; Neoplasms/drug therapy* ; Animals ; Drugs, Chinese Herbal/therapeutic use*

Objective To investigate the effect and mechanism of baicalin on blood lipid metabolism and immune function in rats with gestational diabetes mellitus (GDM). Methods Female rats fed with high-fat and high-sugar diet and male rats fed with ordinary diet were caged together to prepare pregnant rats, and the GDM rat model was established by intraperitoneal injection of streptozotocin (35 mg/kg). GDM rats were randomly divided into a model group, a fasudil (FA) (RhoA/RocK inhibitor) group (10 mg/kg), low-dose (100 mg/kg) and high-dose (200 mg/kg) baicalin groups, and a high-dose baicalin combined with LPA (RhoA/RocK activator) group (200 mg/kg baicalin+1 mg/kg LPA ), with 12 rats in each group. Another 12 pregnant rats fed with high-fat and high-sugar diet were selected as the control group. After 2 weeks of corresponding drug intervention in each group, the level of fasting blood glucose (FBG) was detected by blood glucose meter. The level of fasting insulin (FINS) in serum was detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) in serum, and the levels of immunomodulator tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-10 in peripheral blood were detected by the kit. The histopathological changes of liver were observed by HE staining. The proportion of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The mRNA and protein expressions of Ras homolog gene family member A (RhoA), Rho associated coiled-coil forming protein kinase 1 (ROCK1), and ROCK2 in liver tissue were detected by real-time quantitative PCR and Western blot. Results Compared with the control group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the model group were higher; the level of HDL-C in serum, the percentage of IL-10 levels, CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were lower. Compared with the model group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the the FA group and low-dose and high-dose baicalin groups were lower; the level of HDL-C in serum, IL-10 level, the percentage of CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were higher. LPA could obviously weaken the improvement effects of baicalin on blood lipid metabolism and immune function in GDM rats. Conclusion Baicalin may improve blood lipid metabolism and immune function in GDM rats by inhibiting the RhoA/ROCK pathway.
Animals ; Female ; Diabetes, Gestational/metabolism* ; Pregnancy ; rho-Associated Kinases/genetics* ; Flavonoids/pharmacology* ; Rats ; rhoA GTP-Binding Protein/genetics* ; Lipid Metabolism/drug effects* ; Male ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Blood Glucose/metabolism* ; Lipids/blood* ; Tumor Necrosis Factor-alpha/blood* ; rho GTP-Binding Proteins

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Purpose To investigate the predictive value of chest CT-based radiomics for spread through air spaces in stage T1 peripheral type lung cancer.Materials and Methods A total of 173 patients with surgically pathologically confirmed stage T1 non-small cell lung cancer were retrospectively collected and divided into positive group(49 cases)and negative group(124 cases)according to the presence or absence of spread through air spaces.All lesions were randomly divided into training set(122 cases)and validation set(51 cases)according to the ratio of 7∶3.The primary area of lung cancer(the main body of the lesion),the peripheral infiltrative area(a 5-mm annular area expanding outward along the edge of the lesion)and the tumor margin area(a 5-mm annular area retracting inward along the edge of the lesion)were used as areas of interest to extract imaging histological features.Three imaging histological models were established for the primary area of lung cancer,the peripheral infiltrative area and the tumor margin area,and combined with the morphological features of CT to establish three combined models.The efficacy of each model was evaluated and the optimal model was selected.Results The lobulation signs of positive group was significantly more than that of negative group(χ2=9.946,P=0.002).The area under the curve(AUC)of the imaging histological model based on the three regions of interest were 0.899,0.825,0.840 for the training group and 0.876,0.811 and 0.832 for the validation group,respectively.The model with the highest AUC was the primary tumor imaging model(P=0.043,P<0.001,P=0.017),the AUC of the combined model established by adding the lobar sign were 0.917,0.835 and 0.851,respectively.The AUC of the three regions of interest in the validation group were 0.912,0.832,and 0.845 and the highest AUC was found in the primary tumor area(P<0.001,P=0.017,P=0.049).Conclusion It is feasible to study lung cancer with airway metastasis via CT-based radiomics,taken lobulation signs as the risk predictive factor.

Objective:To understand the relevant situation of people seeking tattoo removal in laser cosmetic clinics.Methods:A face-to-face questionnaire survey was conducted among respondents seeking tattoo removal who visited the Laser Cosmetic Clinic of the Provincial Hospital Affiliated to Shandong First Medical University from June 2021 to May 2022. The questionnaire survey content included 4 categories and a total of 30 questions: basic information of the tattoo respondents, tattoo-related situations, respondents’ cognition of tattoos, and tattoo removal needs. The questionnaire responses were statistically analyzed, and differences were analyzed according to the gender, age of the tattoo respondents, and educational level at the time of tattooing. Descriptive statistical analysis was conducted on the general information of the questionnaire; Mantel-Haenszel chi-square test or Pearson’s chi-squared test were used for the analysis of the difference in the composition ratio of each data.Results:A total of 150 questionnaires were distributed and 142 valid questionnaires were collected. There were 81 male and 61 female tattoo respondents, with an age of (21.8±4.9) years (13-41 years). The result of the survey showed that 52.8%(75/142) of the respondents were minors (<18 years old) at the time of tattooing, and 97.2%(138/142) were <24 years old at the time of tattooing; 67.6% (96/142) regretted the act of tattooing; 73.2%(104/142) of the respondents themselves asked for the removal of tattoos; who removed their tattoos for personal development (joining the army, working, studying) was 68.3%(97/142); only 23.2%(33/142) of the respondents understood the harms of tattoos; and 21.8%(31/142) of the respondents suffered from adverse reactions after getting tattoos. The percentage of respondents who hid their tattoos from their family members was 82.4%(117/142); the percentage of respondents whose family members approved of the tattoos was only 25.4%(36/142). Analysis of variance showed that there was no correlation between the education level of the respondents and their knowledge of the tattoo risks( P>0.05); the reasons for removing tattoos were correlated with the age and gender of the respondents at the time of consultation ( P<0.01); the size of tattoos was correlated with the gender of the respondents ( P<0.01) and the female respondents were more inclined to choose a small tattoo; the age of tattooing of the respondents was correlated with the level of education of the respondents when they had tattooed themselves ( P<0.01), the proportion of tattoos aged <18 years old was highest among respondents with junior high school education at the time of tattooing [76.2%(32/42)], and this proportion tended to decrease significantly as the education level at the time of tattooing increased. Conclusion:The respondents seeking tattoo removal in the laser cosmetic clinic are mainly teenagers. About half of the respondents were minors at the time of tattooing, and most of them were not aware of the tattoo risks. There is a certain correlation between the age of the respondents and their educational background at the time of tattooing. There are certain differences in the reasons for removing tattoos among respondents depending on gender and age. There is no correlation between the educational background of the respondents and their understanding of the tattoo risks.

Objective:To understand the relevant situation of people seeking tattoo removal in laser cosmetic clinics.Methods:A face-to-face questionnaire survey was conducted among respondents seeking tattoo removal who visited the Laser Cosmetic Clinic of the Provincial Hospital Affiliated to Shandong First Medical University from June 2021 to May 2022. The questionnaire survey content included 4 categories and a total of 30 questions: basic information of the tattoo respondents, tattoo-related situations, respondents’ cognition of tattoos, and tattoo removal needs. The questionnaire responses were statistically analyzed, and differences were analyzed according to the gender, age of the tattoo respondents, and educational level at the time of tattooing. Descriptive statistical analysis was conducted on the general information of the questionnaire; Mantel-Haenszel chi-square test or Pearson’s chi-squared test were used for the analysis of the difference in the composition ratio of each data.Results:A total of 150 questionnaires were distributed and 142 valid questionnaires were collected. There were 81 male and 61 female tattoo respondents, with an age of (21.8±4.9) years (13-41 years). The result of the survey showed that 52.8%(75/142) of the respondents were minors (<18 years old) at the time of tattooing, and 97.2%(138/142) were <24 years old at the time of tattooing; 67.6% (96/142) regretted the act of tattooing; 73.2%(104/142) of the respondents themselves asked for the removal of tattoos; who removed their tattoos for personal development (joining the army, working, studying) was 68.3%(97/142); only 23.2%(33/142) of the respondents understood the harms of tattoos; and 21.8%(31/142) of the respondents suffered from adverse reactions after getting tattoos. The percentage of respondents who hid their tattoos from their family members was 82.4%(117/142); the percentage of respondents whose family members approved of the tattoos was only 25.4%(36/142). Analysis of variance showed that there was no correlation between the education level of the respondents and their knowledge of the tattoo risks( P>0.05); the reasons for removing tattoos were correlated with the age and gender of the respondents at the time of consultation ( P<0.01); the size of tattoos was correlated with the gender of the respondents ( P<0.01) and the female respondents were more inclined to choose a small tattoo; the age of tattooing of the respondents was correlated with the level of education of the respondents when they had tattooed themselves ( P<0.01), the proportion of tattoos aged <18 years old was highest among respondents with junior high school education at the time of tattooing [76.2%(32/42)], and this proportion tended to decrease significantly as the education level at the time of tattooing increased. Conclusion:The respondents seeking tattoo removal in the laser cosmetic clinic are mainly teenagers. About half of the respondents were minors at the time of tattooing, and most of them were not aware of the tattoo risks. There is a certain correlation between the age of the respondents and their educational background at the time of tattooing. There are certain differences in the reasons for removing tattoos among respondents depending on gender and age. There is no correlation between the educational background of the respondents and their understanding of the tattoo risks.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.