Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

OBJECTIVE To analyze the relationship between LPR and common pharyngeal diseases and its risk factors.METHODS A total of 280 patients who were admitted to the Inpatient Department of Otolaryngology Head and Neck Surgery or Laryngoscopy Room of the First Affiliated Hospital of Harbin Medical University due to throat discomfort from September 2022 to May 2023 were selected as the study objects.All enrolled patients were required to complete the RSI and RFS scoring scales.According to the 2022 LPRD expert Consensus,RSI>13 and/or RFS>7 were classified as LPR group,and RSI≤13 and RFS≤7 are classified as non-LPR group.Chi-square test was used to analyze the differences in the incidence of common pharyngeal diseases such as upper respiratory tract papilloma,epiglottic cyst,vocal cord polyp,vocal cord leucoplakia,vocal cord cancer and hypopharyngeal cancer among different groups.Univariate Chi-square test analysis and multivariate binary logistic regression analysis were performed for gender,age,BMI,smoking and drinking history.All differences were statistically significant with P<0.05.RESULTS The prevalence of LPR in 280 patients with throat discomfort was 70.0%(196/280).There were statistically significant differences in the incidence of LPR group and non-LPR group in patients with vocal cord polyp(χ2=4.228,P<0.05),vocal cord leukoplakia(χ2=12.283,P<0.05),vocal cord cancer(χ2=4.103,P<0.05)and hypopharyngeal cancer(χ2=4.907,P<0.05),while there was no significant difference in the incidence of LPR group and non-LPR group in patients with papilloma of upper respiratory tract(χ2=0.183,P>0.05)and epiglottic cyst(χ2=0.556,P>0.05).Univariate analysis showed that there were significant differences in the incidence rates of smoking(χ2=20.403,P<0.05)and drinking(χ2=7.704,P<0.05)between the LPR group and the non-LPR group,while gender(χ2=0.01,P>0.05),age(χ2=8.147,P>0.05),BMI(χ2=2.060,P>0.05)had no significant difference.Multivariate logistic regression analysis showed that smoking(OR=3.390,95%CI:1.761-6.526,P<0.05)was an independent risk factor for LPR.CONCLUSION There is a high co-prevalence of LPR with vocal cord polyps,vocal cord leukoplakia,vocal cord cancer and hypopharyngeal cancer.Therefore,LPR should be evaluated when treating throat related diseases,and LPR should be actively treated if necessary.In addition,smoking and drinking are risk factors for LPR,so it is necessary to stop smoking and drinking alcohol when treating LPR.

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

OBJECTIVE To study the anti-ulcerative colitis(UC) effect of Sargentodoxae Caulis and explore its mechanism. METHODS The UC mice model induced by dextran sodium sulfate was used to evaluate the anti-UC effect of Sargentodoxae Caulis. The ingredients of Sargentodoxae Caulis were obtained according to the CNKI and PubMed website, component targets were screened by SwissTargetPrediction database, GEO gene chip was used to extract UC differential genes, then a network of "ingredients-targets-disease" of the Sargentodoxae Caulis was constructed. After screening the core targets, protein interaction and cluster analysis, biological process and pathway enrichment analysis were performed, and the reliability of network analysis was preliminarily verified by molecular docking and literatures. RESULTS Sargentodoxae Caulis could significantly improve the disease activity index score, colon shortening and colonic histopathological changes of UC mice, and had a good anti-UC effect. The network analysis found that the core components of the anti-UC of Sargentodoxae Caulis include (+)-Dihydroxyurearetic acid, Isorhaponigenin and Pinosylvin, and 63 core targets, such as EGFR, STAT1 and LCK, regulating PI3K-Akt signal pathway and cancer proteoglycan and other related signal pathways of immune anti-inflammatory and anti-cancer, and it could affect the biological processes such as amino acid modification, kinase activity regulation, cell reaction and oxidative stress to treat UC. Molecular docking and literature showed that the constructed network had high reliability. CONCLUSION Sargentodoxae Caulis has a good anti-UC effect, and its mechanism may be closely related to the regulation of intestinal immune inflammation and cell proliferation, differentiation and migration. It has the characteristics of multi-component, multi-target and multi-way.

Taking the Ligustrum lucidum extract as an example, this study investigated the influence of external mechanical forces under different processing conditions on the crystallographic solid form and the key parameter of drug dissolution rate, so as to provide guidance for the preparation and quality control of traditional Chinese medicine preparations. Under different pulverization and tableting conditions, the change of crystallographic solid form of L. lucidum extract was observed by polarizing light microscope. Meanwhile, the effect of this change on the dissolution rate was investigated, and the mathematical relationship between crystal content and dissolution rate was analyzed. The results showed that the process of ball milling and tableting had a significant impact on the crystallographic solid form of L. lucidum extract. The amorphous extract displayed crystal transformation, which induced a significant decline in dissolution rate. Further studies revealed that there was a negative linear relationship between crystal content and dissolution rate. The results of this study indicated that the crystallographic solid form transformation of traditional Chinese medicine extracts might occur during the preparation process, which may cause potential risks to the quality of traditional Chinese medicine preparations. It is suggested that we should pay attention to and strengthen the investigation of the crystallographic solid form during the preparation process, so as to guarantee the safety, effectiveness, and quality controllability of traditional Chinese medicine preparations.

Purpose To explore the effect of compressed sensing(CS)technique with different acceleration factors on the quality of cardiac magnetic resonance cine sequences and feasibility of clinical application.Materials and Methods From January to July 2021,40 healthy volunteers were prospectively recruited for cardiac magnetic resonance cine imaging in Hefei First People's Hospital.Four scan protocols of volunteers were designed:SENSE 2 and CS-cine sequences with acceleration factors of 3,4 and 8.The imaging slices include four chamber heart,short axis heart,left ventricular two chamber heart and three chamber heart.Subjective score of image quality,left ventricular cardiac function and 16-segment myocardial thickness of SENSE 2 and CS3,CS4 and CS8 were compared and analyzed.Results Taking SENSE 2 image as the standard score of 5,the scores of CS3 and CS4 were above 3,and the scores of CS8 were below 3.There was no significant difference between the scores of four chamber heart and short axis heart images of CS3 and SENSE 2 sequence(all P>0.05).There were statistically significant differences in the subjective scores of image quality between the left ventricular two chamber heart and three chamber heart groups of each sequence(all P<0.05).There was no statistically significant difference in left ventricular function(left ventricular ejection fraction,left ventricular end systolic volume,left ventricular end diastolic volume,left ventricular stroke volume,left ventricular end-diastolic mass)(F=0.027,0.182,0.057,0.140,0.545)and myocardial thickness(F=0.052-7.366)among the four imaging schemes(all P>0.05).Conclusion Cardiac cine based on compressed sensing technology have good application prospects.With the increase of acceleration factors,the scanning time gradually decreases,and the corresponding image quality will also decrease.When the acceleration factor is 4,that is,the scanning time of the conventional cine sequence is reduced by 50%,the left ventricular function and myocardial thickness can still be accurately measured,and the image quality basically meets the diagnostic requirements.

Objective:To study the application value of narrow-band imaging in the diagnosis of laryngopharyngeal reflux. Methods:A total of 275 patients admitted to the inpatient department or laryngoscopy room of the Otolaryngology Head and Neck Surgery Department of the First Affiliated Hospital of Harbin Medical University from September 2022 to April 2023 due to throat discomfort were selected as the research subjects. All of them completed RSI, RFS scoring scales and electronic laryngoscopy（including ordinary white light and NBI）. According to the expert consensus of LPRD in 2022, RSI and RFS scoring scale were used as diagnostic criteria to divide them into LPR group and non-LPR group. Chi-square test was used to analyze the differences of positive rates of characteristic manifestations under NBI among different groups. The consistency of NBI and scale diagnostic methods was analyzed by Kappa, and RSI and RFS scoring were used as diagnostic criteria, The diagnostic efficiency of NBI method was analyzed. Results:There were 190 people in the LPR group, 157 of whom showed characteristic performance under the NBI mode, with a positive rate of 82.6%（157/190）; there were 85 people in the non-LPR group, with a positive rate of 18.8%（16/85）. There was a statistically significant difference in the positive rate between the two groups（χ²=102.47, P<0.05）. The consistency rate between RSI, RFS and NBI was 82.2%（226/275）. Kappa consistency analysis was used, and Kappa=0.605（P<0.05）, indicating good consistency between the two diagnostic methods. Using RSI and RFS as diagnostic criteria for LPR, the sensitivity of NBI diagnostic method was 82.6%（157/190）, specificity 81.2%（69/85）, positive predictive value 90.8%（157/173） and negative predictive value 67.6%（69/102）. Conclusion:Narrow-band imaging, as a new endoscopic imaging technique, can show small changes in mucosal surface micro vessels and play an important role in the diagnosis of laryngopharyngeal reflux.
Humans ; Laryngopharyngeal Reflux/diagnostic imaging* ; Narrow Band Imaging ; Laryngoscopy/methods* ; Pharynx ; Predictive Value of Tests

OBJECTIVE To analyze the patterns and characteristics of drug-related administrative penalty cases with medical institutions as parties from 2020 to 2022 in order to further improve drug management in medical institutions. METHODS A retrospective statistical analysis was used to summarize the drug-related administrative penalty decisions with medical institutions as parties， and to match them with the provisions of the Drug Administration Law （2019 version） for statistical analysis. RESULTS There were 144 complete administrative penalty decisions with medical institutions as parties. Analyzed by cause， 126 cases of administrative punishment for inferior drugs accounted for 87.50%， of which expired drugs accounted for more than 50.00% of the inferior drug cases； 15 cases （10.42%） were for purchasing drugs from enterprises or individuals not qualified to operate drugs. Analyzed by the range of punishment amount of the cases， 34 cases （23.61%） resulted in lighter penalties， while 81 cases （56.25%） resulted in reduced penalties. CONCLUSIONS There are extremely few medical institutions that have received administrative penalties for drug management violations. Medical institutions should strengthen the awareness of law-abiding， and know the red line of drug management and the illegal behavior that is easy to occur， so as to better strengthen drug quality management.

OBJECTIVE To study the correlation between color and inner quality during the processing of Prunus mume carbon， and provide reference for the determination of processing end point of P. mume carbon. METHODS The chromaticity value of P. mume carbon powder was measured by colorimeter， and the inner quality of P. mume carbon was measured by selecting the contents of water， water-soluble extract， citric acid and tannin. The dynamic change trend of the chromaticity value， water， water- soluble extract， the contents of citric acid and tannin in P. mume carbon under different processing time was analyzed. The correlation between color and the above indexe contents was analyzed， and the regression equation of inner quality-chromaticity value was established. Combined with principal component analysis （PCA）， hierarchical cluster analysis （CA） and partial least squares discriminant analysis （PLS-DA）， the difference of P. mume carbon at different processing times was analyzed to determine the processing end point. RESULTS With the extension of processing time， the sample color gradually deepened； the chromaticity values L* and E* of the samples increased at first and then decreased， the chromaticity values a* and b* decreased， and finally all tended to be stable. The content of water-soluble extract， citric acid and tannin in the sample increased at first and then decreased， the water content of the sample decreased with time and finally stabilized. Correlation analysis showed that water， water-soluble extract， citric acid and tannin were positively correlated with L*， a*， b* and E*（P＜0.001）. PCA and HCA showed that P. mume carbon under different processing time could be clustered into two categories： the processed samples of 0-30 min and those of 40-60 min. PLS-DA showed that water and water-soluble extract were important quality indexes and b* was an important chrominance index in the processing of P. mume carbon. The chromaticity value of the samples processed for 50 min and 60 min were not significantly different. The contents of water， water- soluble extract， citric acid and tannin in the samples processed for 60 min were less than those processed for 50 min. CONCLUSIONS There is a certain correlation between the color and the inner quality of P. mume carbon. The processing time of P. mume carbon should be 40-50 min.