OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.

Objective:To investigate the distribution of iodine and other chemical elements in soil, grain and vegetables in different water iodine areas of Xi'an City, and to provide theoretical basis for prevention and treatment of iodine related diseases and water improvement measures.Methods:From September to November 2021, a stratified cluster sampling method was used to select three survey villages in Xi'an, namely Yehu Village, Xingbei Village, and Quanzhong Village, where the iodine level of residents' drinking water < 10, 10 - 100, and > 100 μg/L. Drinking water samples were collected from seven survey sites based on the source of domestic drinking water to determine the iodine level of the water. At the same time, soil samples of cultivated land, residents' grains (wheat, corn), and vegetables were collected from survey villages to determine the content of 14 elements including calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, selenium, iodine, and fluoride.Results:The iodine level in the water of 7 survey sites in three survey villages was 5.80, 6.40, 25.51, 42.20, 53.90, 111.65, and 177.63 μg/L, respectively. A total of 70 samples of soil, 65 samples of wheat, 76 samples of corn, and 141 samples of vegetables were collected. Among them, the levels of various elements in vegetables and grains were lower than those in the soil. Only calcium and fluoride were higher in vegetables than in grains, while iron, chromium, copper, zinc, selenium, and iodine were lower in vegetables than in grains. According to the range of water iodine level, there were statistically significant differences in the content of calcium, iron, chromium, nickel, copper, zinc, mercury, iodine, and fluoride in soils from different water iodine regions ( Fcalcium, iron, chromium, nickel = 42.04, 13.55, 12.22, 11.20, Hcopper, zinc, mercury, iodine, fluoride = 14.27, 9.19, 14.72, 25.14, 16.50, P < 0.05). The comparison of magnesium, zinc, cadmium, arsenic, and selenium content in wheat showed statistically significant differences ( Fadmium, selenium = 6.34, 3.31, Hmagnesium, zinc, arsenic = 6.12, 11.55, 6.23, P < 0.05). The comparison of calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, iodine, and fluoride content in corn showed statistically significant differences ( Fmagnesium, chromium, nickel, copper, zinc, iodine = 18.89, 13.76, 17.86, 24.17, 28.46, 15.96, Hcalcium, iron, cadmium, lead, arsenic, mercury, fluoride = 11.57, 40.53, 26.50, 33.05, 33.73, 36.01, 29.21, P < 0.05). The comparison of calcium, iron, magnesium, chromium, zinc, cadmium, lead, arsenic, mercury, and selenium content in vegetables showed statistically significant differences ( H = 23.93, 8.12, 10.03, 7.01, 16.09, 18.36, 23.07, 6.51, 27.67, 7.86, P < 0.05). Conclusions:There are significant differences in the distribution of 14 elements in soil, grain, and vegetables in different water iodine regions. In addition to drinking water, precise guidance should also be provided based on the iodine content in soil, grain, and vegetables in different water iodine areas.

OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.

This study aims to determine the therapeutic effect and then elucidate the molecular mechanism of Dietary Yangrong Decoction(DYRT)on blood deficiency syndrome based on net-work pharmacology and study its active compounds.The molecular mechanism of DYRT in the treatment of blood deficiency syndrome was predicted by network pharmacology.The blood defi-ciency of rats was established using cyclophosphamide and acetophenohydrazine jointly,which was divided into a blank control group,a model group,a Men's Yangrong Decoction group(MYRT)(positive control group),a medicinal group and food-based Yangrong Decoction group.The active components were analyzed by liquid chromatography-mass spectrometry(HPLC-MS),the periph-eral hemogram was detected by an automatic biochemical analyzer,the levels of hematopoietic regulatory factors in serum were determined by ELISA,and the relative expression of EPO in kid-ney and PI3K,AKT,GM-CSF in bone marrow were measured by RT-PCR.The results showed that DYRT had 57 active ingredients and 128 potential targets for the treatment of spleen deficien-cy syndrome.1 835 items were obtained by GO enrichment analysis,and 20 pathways were ob-tained by KEGG enrichment analysis;DYRT and MYRT were identified by HPLC-MS to contain 12 same blood active compounds.Animal experiments showed that,compared with the model group,the number of red blood cells,the number of platelets and the content of hemoglobin in the DYRT group were significantly increased,and the number of white blood cells was significantly decreased(P＜0.05).The contents of EPO,IL-3,IL-6 and GM-CSF in serum were significantly in-creased,and the content of TNF-α was significantly decreased(P＜0.05).The relative expression levels of EPO in kidney and PI3K,AKT and GM-CSF mRNA in bone marrow were significantly increased(P＜0.05).Compared with the MYRT group,the number of white blood cells in the DYRT group was significantly reduced,the content of GM-CSF in serum was significantly in-creased,and the content of EPO and GM-CSF mRNA was significantly increased(P＜0.05).In conclusion,DYRT contains the same active compounds as MYRT,which can regulate hematopoi-etic factors,thereby activating the PI3K/AKT pathway to restore hematopoietic function and im-prove the blood deficiency state of the body.

Objective:To explore the regulatory mechanism of OIP5-AS1 in chronic periodontitis(CP).Methods:Human perio-dontal ligament stem cells(PDLSC)were treated with LPS to establish an in vitro model of CP.Real-time quantitative polymerase chain reaction(qRT-PCR)was performed to detect the expression of OIP5-AS1,miR-143-3p and fibroblast growth factor 1(FGF1)mRNA in periodontal ligament tissues and PDLSCs of CP patients and healthy volunteers.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)method was performed to detect cell viability.Enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of inflammatory cytokines interleukin-1 β(IL-1 β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).Western blot was performed to detect Bax,Bcl-2 and FGF1 protein levels.A dual-luciferase reporter assay was performed to validate the targeting relationship between miR-143-3p and OIP5-AS1/FGF1.Results:The expression of OIP5-AS1 and FGF1 were decreased,and the expression of miR-143-3p was increased in CP patients and LPS-treated PDLSCs(P＜0.05).In LPS-treated PDLSCs,OIP5-AS1 overexpression promoted cell viability and inhibited inflammation and apoptosis(P＜0.05).In addition,OIP5-AS1 targeted miR-143-3p and negatively regulated miR-143-3p expression(P＜0.05).In LPS-treated PDLSCs,up-regulation of miR-143-3p attenuated the inhibitory effect of OIP5-AS1 overexpression on LPS-induced PDLSC dam-age(P＜0.05).miR-143-3p targeted FGF1 and negatively regulated FGF1 expression(P＜0.05).FGF1 overexpression attenuated the effect of co-overexpression of miR-143-3p and IP5-AS1 on LPS-induced damage(P＜0.05).Conclusion:OIP5-AS1 may at-tenuate LPS-induced PDLSC inflammatory response and apoptosis and enhance cell viability by regulating the miR-143-3p/FGF1 axis,which may provide a new target for CP therapy.

Objective:To explore the regulatory mechanism of OIP5-AS1 in chronic periodontitis(CP).Methods:Human perio-dontal ligament stem cells(PDLSC)were treated with LPS to establish an in vitro model of CP.Real-time quantitative polymerase chain reaction(qRT-PCR)was performed to detect the expression of OIP5-AS1,miR-143-3p and fibroblast growth factor 1(FGF1)mRNA in periodontal ligament tissues and PDLSCs of CP patients and healthy volunteers.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)method was performed to detect cell viability.Enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of inflammatory cytokines interleukin-1 β(IL-1 β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).Western blot was performed to detect Bax,Bcl-2 and FGF1 protein levels.A dual-luciferase reporter assay was performed to validate the targeting relationship between miR-143-3p and OIP5-AS1/FGF1.Results:The expression of OIP5-AS1 and FGF1 were decreased,and the expression of miR-143-3p was increased in CP patients and LPS-treated PDLSCs(P＜0.05).In LPS-treated PDLSCs,OIP5-AS1 overexpression promoted cell viability and inhibited inflammation and apoptosis(P＜0.05).In addition,OIP5-AS1 targeted miR-143-3p and negatively regulated miR-143-3p expression(P＜0.05).In LPS-treated PDLSCs,up-regulation of miR-143-3p attenuated the inhibitory effect of OIP5-AS1 overexpression on LPS-induced PDLSC dam-age(P＜0.05).miR-143-3p targeted FGF1 and negatively regulated FGF1 expression(P＜0.05).FGF1 overexpression attenuated the effect of co-overexpression of miR-143-3p and IP5-AS1 on LPS-induced damage(P＜0.05).Conclusion:OIP5-AS1 may at-tenuate LPS-induced PDLSC inflammatory response and apoptosis and enhance cell viability by regulating the miR-143-3p/FGF1 axis,which may provide a new target for CP therapy.

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.