Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To assess the deformation of the bladder-neck opening and the impact of the bladder-neck angle(BNA)on urination in male patients by fluid-structure interaction(FSI)analysis.Methods:We established geometric models of the blad-der,prostate and urethra were established,incorporating both normal and enlarged BNAs,and assessed the effects of BNA alteration on urinary flow by FSI simulation of the flow rate and pressure of the urine within the bladder,bladder neck and urethra,and that of pros-tate displacement as well.We retrospectively analyzed the clinical data on 145 male patients from the Second Hospital of Hebei Medical University between June 2020 and June 2023,39 with acute urine retention(the AUR group)and 106 without(the non-AUR group),and evaluate the impact of BNA on urination based on the urinary flow rate and prostate volume.Results:Comparative simulation a-nalysis showed significant differences in the total urethral pressure and flow rate between the normal and enlarged BNA models(P＜0.05).The maximum prostate displacement was found at the bladder neck,with moderate displacement and unchanged urethral diame-ter in the normal BNA model,but significant displacement and a reduced urethral opening diameter in the enlarged BNA model.FSI analysis confirmed an evident impact of enlarged BNA on urination,more significant in the AUR than in the non-AUR patients(P＜0.05).The BNAs in the patients with the maximum urinary flow rate(Qmax)of＜10,10-15 or＞15 ml/s were 83.7°±2.5°,67.5°±1.8° and 65.1°±4.8° respectively,with statistically significant difference between the former one and the latter two groups(P＜0.05).The BNAs in the patients with normal prostate volume or BPH of grade Ⅰ,Ⅱ,Ⅲ or Ⅳ were 65.0°±3.7°,67.2°±3.1°,71.5°±2.0°,82.8°±3.5° and 105.8°±6.0°,respectively(P＜0.05),with statistically significant difference between BPH grades Ⅲ and Ⅳ(P＜0.05)as well as between these two and the other three groups(P＜0.05),but not among the normal prostate volume,BPH grade Ⅰ and BPH grade Ⅱ groups(P＞0.05).Spearman correlation analysis indicated that BNA was strongly correlated with total prostate volume(TPV),transition zone volume(TZV),intravesical prostatic protrusion(IPP),prostatic urethral angle(PUA),IPSS,and Qmax(P＜0.05).Conclusion:Changes in BNA affect urination and are closely associated with the se-verity of prostate hyperplasia.The BNA may be an important anatomical factor for assessing the severity of lower urinary tract symptoms in BPH patients.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To analyze the safety of idarubicin or daunorubicin combined with cytarabine in the treatment of patients with acute myeloid leukemia.Methods The Chinese Biomedical Database,Chinese Journal Full-text Database,Chinese Science and Technology Journal Full-text Database,Wanfang Database,Embase,PubMed,Cochrane Library were searched.The randomized controlled trials(RCTs)of idarubicin combined with cytarabine(treatment group)and daunorubicin combined with cytarabine(control group)were collected.The search time was from 2014-01-01 to 2024-02-23.RevMan 5.4 software was used to perform meta-analysis,sensitivity analysis and publication bias analysis on adverse drug reactions of the included studies.Results A total of 11 RCTs involving 1 818 patients were included in the Meta-analysis.The treatment and control groups were enrolled 912 and 906 cases,respectively.The results of meta-analysis showed that the total incidence of adverse drug reactions in the treatment group and the control group was 22.9％(56 cases/245 cases)and 42.9％(105 cases/245 cases),respectively,and the difference was statistically significant[relative risk(RR)=0.53,95％confidence interval(CI)=0.41-0.69,P＜0.001)].In the specific adverse drug reactions,there were no statistically significant differences in the incidence of hematological toxicity,digestive system toxicity,cardiac toxicity,liver and kidney toxicity,infection,bleeding between the two groups(all P＞0.05).Sensitivity analysis showed that the results were stable and reliable.The results of publication bias analysis showed that this study was less likely to have publication bias.Conclusion The incidence of adverse drug reactions of idarubicin combined with cytarabine in the treatment of patients with acute myeloid leukemia is significantly lower than that of daunorubicin combined with cytarabine,so the former has better safety.

Objective To compare the efficacy and safety of Saccharomyces boulardii and other probiotics in the treatment of pediatric diarrhea.Methods Retrieved from PubMed,Embase,CBM,Wanfang data,CNKI and VIP,randomized controlled trial(RCTs)about Saccharomyces boulardii(treatment group)vs other probiotics(control group)were collected.After screening the literature,extracting data and evaluating the quality,Meta-analysis was performed by using RevMan 5.3 and Stata 17.0 software.Results A total of 30 RCTs were included,involving 3 082 children.Results of Meta-analysis showed there was no statistical significance in the duration of diarrhea[mean difference(MD)=-0.65,95％confidence interval(CI)=-1.44-0.14,P＞0.05]or the total incidence of adverse reactions[odds ratio(OR)=0.85,95％CI=0.44-1.62,P＞0.05].The total effective rate(OR=1.60,95％CI=1.08-2.36,P＜0.05)and the number of stools(MD=-0.66,95％CI=-1.00--0.32,P＜0.01)in the treatment group were significantly better than control group.There was statistically significant difference in the duration of diarrhea between the two groups treated with diarrhea with fever(MD=1.81,95％CI=1.12-2.49,P＜0.01)and rotavirus gastroenteritis(MD=-0.92,95％CI=-1.20--0.64,P＜0.01).In the treatment of diarrhea with fever,the duration of diarrhea in the control group was significantly shorter than that in the treatment group.The duration of diarrhea in the treatment group was significantly shorter than that control group.At the same time,the duration of diarrhea in children with diarrhea treated with treatment group was significantly shorter than that of control group Bifidobacterium tetragenous viable(MD=-0.84,95％CI=-1.09--0.58,P＜0.01)and control group combined Bacillus subtilis and Enterococcus faecium enteric-coated(MD=-1.35,95％CI=-2.30-0.39,P＜0.01).Conclusion The safety of Saccharomyces boulardii are similar to other probiotics.The efficacy and the number of stools with Saccharomyces boulardii are significantly better than other probiotics in the treatment of diarrhea.The duration of diarrhea in Saccharomyces boulardii group was significantly shorter than other probiotics,while in the treatment of antibiotic-associated diarrhea,the duration of diarrhea of Saccharomyces boulardii was the same as that of other probiotics.However,the duration of diarrhea in children with diarrhea treated with Saccharomyces boulardii was significantly longer than other probiotics.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Objective To investigate the role of magnesium ion(Mg2+)in cisplatin-induced acute kidney injury(Cis-AKI)in kidney organoids and HK-2 cells,as well as the potential mechanism.Methods Initially,we utilized human-derived induced pluripotent stem cells(iPSCs)to construct kidney organoids,and then built a Cis-AKI model based on kidney organoids.HE staining was used to observe the structure of kidney organoids,and immunofluorescence staining was used to observe the localization of markers and the expression of cleaved caspase-3.qRT-PCR was conducted to detect mRNA levels of tubular and glomerular markers,as well as inflammatory factors.Subsequently,the kidney organoids were randomly divided into control group,cisplatin group(Cis group),and Mg2+pretreatment group(Cis+Mg2+group).CCK-8 and ATP content assays were employed to evaluate the cell viability of renal tubular epithelial cells.TUNEL staining was performed to detect the apoptosis of renal tubular epithelial cells.Western blot was utilized to detect the expression of apoptosis-associated proteins(Bcl-2,Bax,cleaved caspase-3)and organic cation transporter 2(OCT2).Immunofluorescence was used to detect the localization and expression of OCT2.Results On the 10th day,the tubular structure in kidney organoids was visible,with abundant expression of renal markers.Treatment with 10 μmol/L cisplatin resulted in structural damage to kidney organoids,significantly increased expression of cleaved caspase-3 and mRNA levels of inflammatory factors,and significantly decreased ATP content.Compared with the Cis group,the Cis+Mg2+group showed increased ATP content in kidney organoids,reduced number of TUNEL-positive cells,significantly decreased expression of apoptosis-associated proteins,and significantly decreased expression of OCT2.However,there was no significant improvement in HK-2 cell viability,the number of TUNEL-positive cells,or apoptosis-associated proteins in the Cis+Mg2+group,and HK-2 cells did not express OCT2.Conclusion Kidney organoid is an ideal in vitro model to study the pathogenesis and treatment of Cis-AKI.Mg2+pretreatment can significantly reduce the damage of kidney organoids induced by cisplatin,and the mechanism may be related to the downregulation of OCT2.