Root caries is a prevalent chronic oral disease with an average global prevalence of 41.5%, characterized by high incidence, low rate of treatment, and high rate of retreatment. Root caries is primarily caused by core microbiome-induced dysbiosis and has multiple risk factors, including gingival recession, root surface exposure, and salivary dysfunction. The traditional preventive measures and treatments such as fluoride, mineralizing agents, and restorative materials, are unable to restore or maintain oral microecological homeostasis. Recent studies have demonstrated that probiotics, prebiotics, synbiotics, and antimicrobial peptides may prevent and treat root caries by reversing dysbiosis. In addition, these biotherapeutics can reduce acid production by acidiferous bacteria, promote alkali production (hydrogen peroxide and ammonia) by alkali-producing bacteria, inhibit biofilm formation, decrease extracellular polysaccharide production, and suppress microbial adhesion and aggregation. It is expected to play an important role in the prevention and control of root caries. This article aims to review oral probiotics (Streptococcus oligofermentans, Streptococcus oralis subsp. dentisani, and Streptococcus salivarius), prebiotics (arginine, nitrates, and synthetic compounds), synbiotics, and antimicrobial peptides (gallic acid-polyphemusin I and LH12) to provide evidence and guidance for root caries management through microecological modulation.

Objective To evaluate the efficacy and safety of budesonide combined with pulmonary surfactant(PS)in the treatment of meconium aspiration syndrome(MAS)in neonates.Methods PubMed,Cochrane Central Register of Controlled Trials(Central),Embase,Web of Science,SinoMed,VIP,WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials(RCTs)of budesonide combined with PS in the treatment of neonatal MAS from inception to September 2,2023.Two researchers independently screened literature,extracted data and assessed the risk of bias of the included studies,meta-analyses were performed by using the RevMan 5.4 software.Results A total of 6 RCTs involving 544 patients were included.The results of meta-analysis showed that compared with PS group,budesonide combined with PS group had higher overall effective rate(RR=1.29,95％CI 1.17 to 1.41,P＜0.001),shorter hospital stay(MD=-6.35,95％CI-9.25 to-3.46,P＜0.001)and shorter time of oxygen inhalation(MD=-1.61,95％CI-2.23 to-0.98,P＜0.001),shorter the duration of ventilator use(MD=-26.46,95％CI-35.98 to-16.95,P＜0.001),improved the blood gas analysis indexes at each time after treatment(P＜0.05);In terms of safety,the incidence of total complications and adverse reactions in budesonide combined with PS group was significantly lower(RR=0.35,95％CI 0.25 to 0.47,P＜0.001).Subgroup analysis showed that the incidence of persistent pulmonary hypertension of the newborn(PPHN)in the budesonide combined with PS group was decreased(RR=0.38,95％CI 0.19 to 0.74,P=0.004),and the incidence of pneumorrhagia was decreased(RR=0.26,95％CI 0.10 to 0.69,P=0.007),and the difference was statistically significant;the incidence of heart failure and sepsis was not statistically significant compared with the PS group(P＞0.05).Conclusion Current evidence shows that budesonide combined with PS in the treatment of neonatal meconium aspiration syndrome can improve the symptoms and signs of MAS children,improve the blood gas analysis index,accelerate disease rehabilitation,shorten the course of the disease,can help reduce the risk of complications and PPHN,pneumorrhagia,and doesn't increase the incidence of heart failure,sepsis.Due to the limited quantity of the included studies,more high-quality and large-sample RCTs are needed to further validate the above conclusions.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Objective:To investigate the effect of IKKε on autophagy during abdominal aortic aneurysm formation in mice.Methods:We stimulated ApoE -/- mice and ApoE -/-IKKε -/- mice with AngⅡ and saline for 28 days. Metaboilic levels and aortic diameter of ApoE -/- mice and ApoE -/-IKKε -/- mice were measured. The arterial fibrosis of mice was detected by Masson staining and HE staining, mitochondrial reactive oxides were detected by fluorescence assay, the expression levels of autophagy factors LC3B and Beclin-1 were detected by immunohistochemistry, and the protein level of LC3B was detected by Western blot. Results:There was no significant difference in metaboilic levels between ApoE -/- mice and ApoE -/- IKKε -/- mice. However, the aortic diameterf ApoE -/-IKKε -/- mice was significantly less than that of ApoE -/- mice. The fibrosis level of ApoE -/-IKKε -/- mice was significantly lower than that of ApoE -/- mice. Furthermore, ROS in ApoE -/-IKKε -/- mice was lower than that in ApoE -/- mice. In addition, immunohistochemical and western blot showed that the expression levels of LC3B and Beclin-1 in ApoE -/-IKKε -/- mice were significantly lower than in ApoE -/- mice. Conclusion:IKKε -/- deficiency can significantly inhibit autophagy, thus reducing the development of abdominal aortic aneurysm in mice.

Objective:To assess the value of amide proton transfer weighted (APTw) imaging in the evaluation of pH changes in infarct core (IC) and ischemic penumbra (IP) in subacute cerebral infarction.Methods:The data of twenty-three subacute cerebral infarction patients with unilateral steno-occlusive disease of the middle cerebral artery (subacute infarction group) from April to November 2019 in the First Affiliated Hospital of Dalian Medical University were prospectively analyzed. Fifteen healthy volunteers were enrolled in this study as the control group. All subjects underwent conventional MRI, DWI, 3D-pseudo continuous arterial spin labeling (3D-pCASL) and APTw sequences. Based on DWI images, relative cerebral blood flow (rCBF) and APTw images to determine the region of IC, blood flow penumbra [cerebral blood flow(CBF)-DWI mismatch area, IP CBF] and metabolic penumbra (APTw-DWI mismatched area, IP APT). 3D ROIs were used to semi-automatically measure the APTw signals and the volume of IC and IP CBF of the patients in subacute infarction group. The comparison of APTw signals between the infarct side and the contralateral side in the subacute infarction group, the comparison of bilateral APTw signals in the control group, and the comparison of APTw signals in the IC and IP CBF regions were performed by paired-sample t test or Wilcoxon signed-rank test. The paired-sample t test or Mann-Whitney U test was used to compare the APTw signals between the two groups. The Friedman test was applied to compare the difference of volumes among IP CBF1.5, IP CBF2.5 and IP APT . Results:There was no significant difference of the APTw signals among the IC, the contralateral side in the subacute infarction group and the control group ( P>0.05). The APTw signals of IP CBF and IC of the infarction group were statistically different ( P<0.05). Compared with the contralateral side of IP CBF1.5 (3.7±1.7, -1.84±1.48, 5.57±2.75), the APTwmax (3.07±1.41, t=-3.012, P=0.006), APTw min [-1.30 (-1.74, -0.57), Z=-2.099, P=0.036], and APTwmax-min(4.51±2.58, t=-3.273, P=0.003) signals in the IP CBF1.5 were decreased ( P<0.05). Compared with the contralateral side of IP CBF2.5 [-1.53 (-2.80, -0.91), 5.31±2.61], the APTw min [-1.08 (-1.60, -0.49), Z=-2.616, P=0.009] and APTwmax-min (4.41±2.72, t=-3.228, P=0.004) signals in the IP CBF2.5 were decreased. The volumes of IP CBF1.5 [107.51(50.08, 138.61)mm 3], IP APT [99.00 (53.27, 121.335) mm 3] and IP CBF2.5 [89.91 (51.53, 139.87) mm 3] were successively reduced (χ2=7.913, P=0.019), and the volume of IP CBF2.5 was significantly smaller than that of IP CBF1.5 ( P=0.037). Conclusion:The acid-base metabolism in the IC of subacute cerebral infarction is not obvious, but the blood flow penumbra has local acid-base metabolism imbalance, and the range of metabolic penumbra coincides with the blood flow penumbra.

Objective: To study the hearing status and analyze the related influencing factors in noise-exposed workers in an automobile manufacture enterprise, and put forward suggestions for prevention of noise-induced hearing loss. Methods: Noise exposure level testing, audiometry testing and questionnaires were performed for noise exposed workers in the automobile manufacture enterprise. To analyze the relationship between different factors and noise-induced hearing loss by cumulative noise exposure(CNE) calculated 8-hour continuous A-weighted equivalent noise level and seniority. Results: The detection rate of hearing loss in noise-exposed workers was 22.8%. The noise exposure intensity of stamping workshop is higher than other workshop, and the hearing loss detection rate of stamping workshop workers is higher than other workshop workers. The detection rate of hearing loss has significant difference in L_{Aeq·8 h}, seniority, CNE, age, high temperature and wearing earplugs (P<0.05). The results of logistic regression analysis showed that CNE, age and high-temperature were risk factors for noise-induced hearing loss (P<0.05 and OR>1) and there was an increasing tendency of hearing loss with increase in length of service and CNE, while using of earplugs was a protective factor (P<0.05 and OR<1). With the increase of CNE, the incidence of hearing loss is the rising trend. Conclusion It is suggested to strengthen the noise control and individual protection and improve the high-temperature working environment, which plays an important role in reducing the occurrence of noise-induced hearing loss.

The quality control processes for herbal medicines have been problematic. Flavonoids are the major active components of Huangqin Tang (HQT, a traditional Chinese medicine formula). In this study, we used a combinative method approach consisting of chromatographic fingerprinting (high performance liquid chromatography; HPLC), quantitative methods and a pharmacodynamic evaluation model to analyze the flavonoids of HQT obtained from different sources. Ten batches of HQT were analyzed by the HPLC fingerprinting method and 26 common peaks were detected, of which 23 peaks corresponded with the chemical profile of HQT. In addition, 11 major compounds were identified by LC-MS analysis (liquid chromatography-tandem mass spectrometer; LC-MS (n) ) and quantified by the HPLC quantitative method approach. The studied 10 batches of HQT were found to be homogeneous in their composition with a similarity between 0.990 and 1.000. The distribution of the 11 identified compounds was found to be very similar among the batches. Only slight pharmacodynamic differences were detected between the different batches, confirming the homogeneity of HQT. The results of this study prove that the combination of chromatographic fingerprinting and quantitative analysis can be readily used for comprehensive quality control of herbal medicines.

To investigate the effect of huangqin tang on expression of cytokines and NF-κB p65 in rats with ulcerative colitis (UC), and to probe into its underlying mechanisms of action. The mode of UC rats with cell immunoreactivity was made using compound method (trinitrobenzene sulfonic acid and ethanol). Rats were randomly divided into control group, model group, SASP group and high dose, middle dose and low dose of huangqin tang group. The food intake, body weight and microscopic damage of rats in each group were evaluated after being treated for five days. The blood and colon tissue were also collected. Production of NO was detected by Griess assay, the expression levels of IL-6, TNF-α, PGE2 were detected by ELISA. ICH method was undertaken to determine the expression of NF-κB p65 protein in colon tissue. The food intake and body weight of model group rats were lower than that of control group. The expression levels of NO, IL-6, TNF-α, PGE2 in serum and NF-κB p65 protein of colon tissue in model group were higher than that of control group. The above indexes were ameliorated in high and middle dose of huangqin tang groups. But there was no significant difference with SASP group. NF-κB p65 may be involved in the pathogenesis of UC, and huangqin tang can inhibit the relative activity of NF-κB p65, and decrease the expression levels of NO, IL-6, TNF-α and PGE2.

Objective To investigate the effects of Saussurea involucrate by cell culture on increasing the calcium content and bone density after 90 days feed in ovariectomized rats. Methods Osteoporosis model rats were induced by ovariectomy, treated with 16.7、33.3、100 mg/(kg?d)cell culture of Saussurea involucrate for 90 days. Body weight was observed, calcium content was measured through atomic absorption method and the bone density was detected by bone sonometers. Results cell culture of Saussurea involucrate(16.7、33.3、100 mg/kg)can increase the calcium content[(380.1 ± 1.9)mg/g、(370.7 ± 1.1)mg/g、(363.5 ± 2.4)mg/g] significantly(P<0.01)than the model group; increase distal femoral bone mineral density[(0.041 ± 0.017)g/cm2、(0.042±0.023)g/cm2、(0.040±0.008)g/cm2] significantly(P<0.01 or 0.05) than the model group(0.022±0.014)g/cm2; and also increase the middle femoral bone mineral density, the low-dose group (0.305±0.030)g/cm2 significantly (P<0.05) than the model group(0.259±0.061)g/cm2. Conclusion The cell culture of Saussurea involucrate has the effect of increasing the bone density.

The pharmacodynamic (PD) and pharmacokinetic (PK) properties of Huangqin Tang (HQT) were investigated in yeast-induced febrile rats. Blood sample and rectal temperature data of the rats were collected at different times after single oral administration of HQT at 20 g x kg(-1). The plasma concentrations of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid were quantified by a sensitive liquid chromatography-tandem mass spectrometric (LC-MS) method. The blood concentrations of PGE2, 1L-1β and TNF-α were detected by radioimmunoassay (RIA). All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The potential relationship between the mean concentration of eight constituents and the antifebrile efficacy was investigated by calculating Pearson correlation coefficients. It was found that HQT had significant antifebrile efficacy in yeast-induced febrile rats, but had no effect to normal rats. The antifebrile effect of HQT can be attributed to the inhibition of PGE2, 1L-1β and TNF-α. The constituents (baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid) in febrile rats had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC than those in normal rats. Febrile condition could affect the pharmacokinetic behaviour of HQT in vivo; the flavonoids with the same backbone showed the similar fate in the body; baicalein and wogonin had a strong positive correlation (R > 0.66, P ≤ 0.02) with the antifebrile efficacy determined. Together, these constituents demonstrated different pharmacokinetic properties in the febrile body.