OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Background With the progression of industrialization, an increasing number of emerging contaminants are entering aquatic environments, posing significant threats to the safety of drinking water. Therefore, establishing a system for identifying unknown hazardous factors and implementing safety warning mechanisms for drinking water is of paramount importance. Among these efforts, non-target screening plays a critical role, but its effectiveness is largely constrained by the scope of coverage of sample pre-treatment methods. Objective To integrate modern chromatography/mass spectrometry techniques with advanced data mining methods to develop a non-discriminatory sample pre-treatment method for comprehensive enrichment of unknown contaminants in drinking water, laying a technical foundation for the discovery and identification of unknown organic hazardous factors in drinking water. Methods A non-discriminatory pre-treatment method based on supramolecular and solid-phase extraction was developed. The final target compounds including 333 pesticides, 194 pharmaceuticals and personal care products (PPCPs), and 59 per- and polyfluoroalkyl substances (PFASs) were used for optimizing the pre-treatment method, confirming its coverage. The impacts of different eluents on the absolute recovery rates of target compounds were compared to select the conditions with the highest recovery for sample pre-treatment. The effects of different supramolecular solvents and salt concentrations on target compound recovery were also evaluated to determine the most suitable solvent and salt concentration. Results The solid-phase extraction elution solvents, supramolecular extraction solvents, and salt concentrations were optimized based on the target compound recovery rates. The optimal recovery conditions were achieved using 2 mL methanol, 2 mL methanol (containing 1% formic acid), 2 mL ethyl acetate, 2 mL dichloromethane, hexanediol supramolecular solvent, and 426 mg salt. The detection method developed based on these conditions showed a good linear relationship for all target compounds in the range of 0.1-100.0 ng·mL⁻¹, with R² > 0.99. The method’s limit of detection ranged from 0.01 ng⁻¹ to 0.95 ng⁻¹, and 95% of target compounds were recovered in the range of 20%-120%, with relative standard deviation (RSD) less than 30%, indicating good precision. Conclusion The combined pre-treatment method of solid-phase extraction and supramolecular solvent extraction can effectively enrich contaminants in drinking water across low, medium, and high polarities, enabling broad-spectrum enrichment of diverse trace contaminants in drinking water. It provides technical support for broad-spectrum, high-throughput screening and identification of organic pollutants in drinking water, and also serves as a reference for establishing urban drinking water public safety warning systems.

ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days， and samples were collected on days 0， 2， 4， 6， 8， and 10. The changes of biomass， effective components， primary metabolites， secondary metabolites， antioxidant enzymes， and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group， the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group， the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%， respectively. On the other hand， the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone， which showed increases of 14.6% and 1.6%， respectively， in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites， while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

BACKGROUND:At present,it is found that both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology can repair damaged blood vessels,promote vascular regeneration,rebuild blood supply in the femoral head,restore normal blood supply,and further promote osteogenesis.Both of them have certain advantages in early intervention of steroid-induced necrosis of femoral head.It can also further understand the mechanism of blood activating and stasis removing herbs and platelet-rich plasma technology in improving steroid-induced necrosis of the femoral head,and provide new ideas for future treatment. OBJECTIVE:To review the research progress of the mechanism of the combination of blood activating and blood stasis removing herbs and platelet-rich plasma technology on steroid-induced necrosis of the femoral head according to the related literature at home and abroad. METHODS:PubMed,Web of Science,Metstr,CNKI and WanFang databases were searched for relevant articles."Traditional Chinese medicine,signal pathways,steroid induced necrosis of femoral head,vascular endothelial growth factor,platelet rich plasma"were used as the Chinese and English search terms separately.The time limit for searching the literature was from January 2000 to July 2022,and 75 related articles were finally included. RESULTS AND CONCLUSION:Both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology have certain advantages in intervening the early stage of steroid-induced necrosis of femoral head.For traditional Chinese medicine,both single and compound drugs can effectively alleviate the further development of steroid-induced necrosis of the femoral head.The specific mechanism is as follows:(1)The traditional Chinese medicine for activating blood circulation and removing blood stasis has a significant anticoagulation effect,which can antagonize the abnormal(hypercoagulable)state of blood caused by hormone drugs,and further restore the normal blood supply in the femoral head.(2)Traditional Chinese medicine for activating blood circulation and removing blood stasis can repair damaged vascular endothelium,regenerate blood vessels and remodel blood supply in the femoral head by activating vascular endothelial growth factor.(3)The traditional Chinese medicine of promoting blood circulation and removing blood stasis has the obvious effect of removing blood stasis,which can reduce the accumulation of fat cells in the bone marrow cavity and relieve the pressure in the femoral head.(4)Traditional Chinese medicine for promoting blood circulation and removing blood stasis can regulate relevant signal pathways,maintain bone metabolism,promote the differentiation and balance of osteoblasts and osteoclasts,and effectively reduce steroid-induced necrosis of the femoral head.In addition,platelet-rich plasma contains a large amount of high concentration of cell growth factor,which plays a positive role in osteogenesis and vascular regeneration,and can also improve the abnormal state of the blood.Traditional Chinese medicine for activating blood circulation and removing blood stasis combined with platelet-rich plasma technology can play their biological roles,and the intervention effect is more significant.

Background Natural pyrethrins have long been widely used in the fields of environmental and household hygiene. Studies have reported that natural pyrethrins have potential liver toxicity, but their specific mechanisms are still unclear yet. Objective To explore the effect of natural pyrethrins on DNA damage in human liver cells. Methods This study used human liver cell QSG7701 as an in vitro testing model. After exposure to DMSO and a series of concentrations of natural pyrethrins (5, 10, 20, and 40 μg·mL⁻¹) for 6 and 24 h, reactive oxygen species (ROS) was detected by fluorescence microscopy using a fluorescence probe, thiobarbituric acid reactive substance (TBARS) by colorimetric method using a microplate reader, DNA damage by comet assay through observing DNA fragment migration under microscope, and phospho H2AX (γH2AX) and 8-oxoguanine (8-oxoG) by immunofluorescence assay using a laser confocal microscope. Results As the exposure concentration of natural pyrethrins increased, the fluorescence intensity of ROS significantly increased in a concentration-dependent manner. The differences in ROS between the 10 μg·mL⁻¹ and above groups and the control group were statistically significant (P<0.01), and the ROS levels in the 20 μg·mL⁻¹ and 40 μg·mL⁻¹ treatment groups were 2.17 and 3.05 times higher than that in the control group respectively. The TBARS level increased in a concentration-dependent manner in natural pyrethrins treated cells (P<0.01), and the levels in the 20 μg·mL⁻¹ and 40 μg·mL⁻¹ treatment groups were 2.46 and 3.01 times higher than that in the control group respectively. The results of comet assay showed trailing formation of cellular DNA in each dose group; as the exposure concentration of natural pyrethrins increased, indicators such as tail DNA content (TDNA%), tail length (TL), tail moment (TM), and Olive tail moment (OTM) increased in a concentration-dependent manner. Compared with the control group, the differences in the indicators between the 20 μg·mL⁻¹ and above groups and the control group were statistically significant (P<0.01), especially in the 40 μg·mL⁻¹ treatment groups, where TDNA%, TL, TM, and OTM were (46.92 ± 3.52) %, (64.67± 4.16) μm, 30.96 ± 2.94, and 22.64 ± 3.89, respectively. The cellular immunofluorescence results showed that natural pyrethrins induced the formation of γH2AX and 8-oxoG, the fluorescence intensities of γH2AX and 8-oxoG increased in a concentration-dependent manner, and the differences between the 10 μg·mL⁻¹ and above groups and the control group were statistically significant (P<0.01). Conclusion Natural pyrethrins could induce DNA damage in human liver cells, and ROS-mediated oxidative stress may play an important role in its liver cell genotoxicity.

Objective: To explore the characteristics of executive function of developmental dyslexic children and the relationship with social adaptability, in order to provide a scientific basis for promoting healthy development of developmental dyslexic children. Methods: From June to September 2023, 85 students in the developmental dyslexia group, 85 students in the biological agematched group and 85 students in the reading levelmatched group were selected from the third to sixth grades of two elementary school in a region of Xinjiang by cluster random sampling method. Their executive function was assessed by the Stroop procedure, the 2-back procedure and the numerical conversion procedure, respectively, and their social adaptive ability was assessed by the Social Adaptation Scale for Children and Adolescents. An analysis of variance (ANOVA) was used to compare the differences in executive function and social adjustment among the three groups, and Pearsons correlation was used to analyze the relationship between executive function and social adjustment in developmental dyslexic children. Results: Children in the developmental dyslexia group had lower correctness on the Stroop colorword task (0.72±0.21), the 2-back task (0.32±0.13), the digitswitching task (0.54±0.16) and the total score of social adjustment (165.39±31.36) than children in the biological agematched (0.80±0.19,0.38±0.11,0.61±0.15,181.71±31.85) and reading levelmatched group (0.79±0.17,0.35±0.07,0.58±0.15,175.71±27.48) (F=4.54,5.05,4.97,6.31,P<0.01). The inhibition (Stroop colorword task correct rate) and conversion subcomponent (digitswitching task correct rate) of the executive function of children in the developmental dyslexia group were both positively correlated with their social adaptive ability (r=0.34,0.43), and the refreshing subcomponent of the executive function (2-back task correct rate) was negatively correlated with their social adaptive ability (r=-0.27) (P<0.05). Conclusions Children with developmental dyslexia have executive function deficits and social maladjustment, and their executive function is related to social adjustment. Measures should be taken to improve the executive function of developmental dyslexic children and to improve their social adaptation.

Objective To investigate the association of sleep disorders with the development and progression of nonalcoholic fatty liver disease(NAFLD).Methods A total of 1 868 participants from the health examination cohort and fatty liver cohort of Beijing Friendship Hospital from June 2022 to June 2023 were enrolled as subjects.Related data were collected from all subjects,including age,sex,education level,chronic medical history,and biochemical parameters,and all subjects completed Pittsburgh Sleep Quality Index(PSQI)scale independently.According to the diagnostic criteria,the subjects were divided into non-NAFLD group with 1 122 subjects and NAFLD group with 746 subjects,and according to the stage of progression,the patients in the NAFLD group were further divided into simple fatty liver group(SFL group with 624 subjects)and nonalcoholic steatohepatitis(NASH)group with 122 subjects.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between three groups.The chi-square test was used for comparison of categorical data between the three groups.The binary Logistic regression analysis was used to investigate the association between sleep factors and NAFLD,and the multinomial Logistic regression analysis was used to investigate the association between sleep factors and the different stages of NAFLD;two multivariate models were constructed for adjustment of potential confounding factors,i.e.,an age-sex adjustment model and a multivariate adjustment model,and the multivariate adjustment model adjusted the factors of age,sex,education level,smoking,diabetes,hypertension,body mass index(BMI),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C).Results There were significant differences in age,sex,BMI,education level,smoking,diabetes,hypertension,alanine aminotransferase,TG,and HDL-C between the non-NAFLD,SFL,and NASH groups(all P<0.05).There were also significant differences between the three groups in the total score of PSQI scale and the proportion of subjects with a score of 0—3 points for the 7 sleep components(all P<0.05).The multivariate adjustment model showed no significant association between sleep disorders and SFL,while long sleep latency(odds ratio[OR]=4.04,95%confidence interval[CI]:2.33—7.03,P<0.001),short sleep duration(OR=3.53,95%CI:1.83—6.82,P<0.001),and severe sleep disorders(OR=2.96,95%CI:1.48—5.93,P=0.002)were closely associated with the risk of NASH.Conclusion Overall sleep condition and its components of sleep disorders are not significantly associated with the simple fatty liver;however,long sleep latency,short sleep duration,and severe sleep disorders can increase the risk of NASH,which should be taken seriously in clinical practice.

OBJECTIVE To observe the clinical efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced liver cancer. METHODS Sixty patients with advanced liver cancer who were treated in our hospital from March 2020 to November 2021 were selected as the study subjects， and then were randomly divided into study group and control group， with 30 cases in each group. The control group was treated with Sorafenib tosylate tablets orally （0.4 g，bid）， and the study group was additionally given Camrelizumab for injection intravenously （200 mg， every 3 weeks） based on the control group； for all patients， the treatment was stopped until disease progression or intolerable side effects occurred. The clinical efficacy， progression-free survival （PFS）， total survival （OS） and 1-year survival rate of the two groups were compared， and the incidence of adverse reactions in two groups， and immune-related adverse reactions in the study group during treatment were recorded. RESULTS The objective remission rate of the study group was significantly higher than the control group （36.7% vs. 13.3%， P＜0.05）， and the median OS and median PFS were significantly longer than the control group （OS： 12.6 months vs. 7.9 months； PFS： 8.2 months vs. 5.3 months， P＜0.05）. There was no significant difference in the 1-year survival rate and the incidence of elevated aspartate aminotransferase and alanine aminotransferase， rash or pruritus， anorexia， diarrhea， fatigue and hypertension between the two groups （P＞0.05）. The adverse events immune-related in the study group mainly included 21 cases of reactive capillary hyperplasia （70.0%）， 6 cases of hypothyroidism （20.0%）， and 1 case of immune-associated pneumonia （3.3%）， which were improved or tolerable after symptomatic treatment. CONCLUSIONS Camrelizumab combined with sorafenib in the treatment of advanced liver cancer can effectively control and delay the disease progression， prolong the survival period of patients， and the adverse reactions can be tolerated.