Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the effect of final vowel types on the voice onset time(VOT)of differ-ent stops in children with hearing impairment,and to provide a basis for the acquisition and correction of stop sounds.Methods A total of 22 hearing-impaired children aged 3～6 and 22 children with normal hearing were ran-domly selected-18 consonant-vowel(CV)syllables composed of 6 stops and 3 single finals were recorded,using first tone.Using Praat 6.1.29 software to analyze and extract the stops VOT.Two-way ANOVA was used for each stop,the dependent variable was VOT,and the independent variables were hearing status and final type.Results Children in the hearing-impaired group had articulation errors in/t/,/g/,and/k/.Hearing status had significant effect on the main effect of plosives/g/,/p/,/t/,/k/(P＜0.05),and the VOT of slurs/g/,/p/,/t/,/k/in the normal hearing group significantly greater than the hearing-impaired group(P＜0.05).The main effect of finals on the VOT of the stops/b/,/p/and/t/was significant(P＜0.05).Hearing status and final type had an interac-tive effect on the stop/t/,and the simple main effect showed that the difference in VOT of/ti/between the hear-ing-impaired group and the normal hearing group was greater than that of/ta/and/tu/.Conclusion The stops/g/,/p//t/,/k/VOT of hearing-impaired children are smaller than those of with normal hearing.The difference in VOT of/ti/sound between the hearing impaired group and the normal hearing group is greater than that of/ta/sound and/tu/sound.In the teaching of the initial/t/sound for hearing-impaired children,we can start with/ta/and/tu/with less difference,and the/ti/sound is consolidated later.Pay attention to breathing and oral exercise training,to lay a good foundation for clear pronunciation.

Objective:To describe the epidemiological distribution of hemorrhoids in a physical exami-nation population in China,which could provide evidence for precision prevention and early intervention of hemorrhoids.Methods:Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design,which collected information by a questionnaire and physical examination results from each subject.The epidemiological distribution of hemorrhoids was described using Logistic models.The gender-,age-,and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China(2010).Results:A total of 2 940 295 adult subjects were included in the study,of whom the average age was(41.7±14.0)years,and 52.6％were females.The standardized detection rate of hemorrhoids was higher for females(43.7％)than that for males(17.7％;P＜0.001)in this study.In the females,the age distribution of hemorrhoids was inverted U-shaped,with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years(63.5％).In the males,the standardized detection rate of hemorrhoids increased along with age,with the highest percentage of 17.2％in the age group of 50-59 years,and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly(P＜0.001 for trend test).The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females(P＜0.001).The standardized detection rate of hemorrhoids showed a positive corre-lation with body mass index(P＜0.001 for trend test in males).Conclusion:The detection rate of hemorrhoids varied to gender,age,obesity,and hypertension status,which could help to identify the risk factors and the high-risk sub-groups,and hence to strengthen health education and early detection accordingly,which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population.This study was conducted in a physical examination population,and the conclusions of this study should be extrapolated with caution.

Objective:To investigate the effect of hyperbaric oxygen（HBO）combined with rosuvastatin on the levels of D-dimer（D-D），lipoprotein-associated phospholipase A2（Lp-PLA2），and high-sensitivity C-reactive protein（hs-CRP）in patients with type 2 diabetes mellitus（T2DM）combined with coronary heart disease（CHD）.Method:The clinical data of 167 T2DM patients combined with CHD admitted to Linyi Central Hospital from July 2019 to July 2021 were retrospectively analyzed. They were divided into two groups according to different treatment methods. The control group（ n=78）was given conventional treatment and oral rosuvastatin，and the study group（ n=89）was treated with HBO on the basis of the treatment in the control group. The effective rate，blood viscosity，and the levels of D-D，Lp-PLA2，and hs-CRP were compared between the two groups. Results:After treatment，the effective rate in the study group［93.23%（83/89）］was significantly higher than that of the control group［82.05%（64/78）］，and the difference was statistically significant（ P<0.05 or P<0.01）；the serum levels of D-D，Lp-PLA2，hs-CRP，and blood viscosity in the study group were significantly lower than those of the control group，and the differences were statistically significant（ P<0.05 or P<0.01）. Conclusion:HBO combined with rosuvastatin in the treatment of T2DM patients combined with CHD can be more effective than using rosuvastatin alone in reducing D-D，Lp-PLA2，hs-CRP levels，and blood viscosity，thus achieving better clinical efficacy.

Objective:To investigate the effect of hyperbaric oxygen（HBO）combined with rosuvastatin on the levels of D-dimer（D-D），lipoprotein-associated phospholipase A2（Lp-PLA2），and high-sensitivity C-reactive protein（hs-CRP）in patients with type 2 diabetes mellitus（T2DM）combined with coronary heart disease（CHD）.Method:The clinical data of 167 T2DM patients combined with CHD admitted to Linyi Central Hospital from July 2019 to July 2021 were retrospectively analyzed. They were divided into two groups according to different treatment methods. The control group（ n=78）was given conventional treatment and oral rosuvastatin，and the study group（ n=89）was treated with HBO on the basis of the treatment in the control group. The effective rate，blood viscosity，and the levels of D-D，Lp-PLA2，and hs-CRP were compared between the two groups. Results:After treatment，the effective rate in the study group［93.23%（83/89）］was significantly higher than that of the control group［82.05%（64/78）］，and the difference was statistically significant（ P<0.05 or P<0.01）；the serum levels of D-D，Lp-PLA2，hs-CRP，and blood viscosity in the study group were significantly lower than those of the control group，and the differences were statistically significant（ P<0.05 or P<0.01）. Conclusion:HBO combined with rosuvastatin in the treatment of T2DM patients combined with CHD can be more effective than using rosuvastatin alone in reducing D-D，Lp-PLA2，hs-CRP levels，and blood viscosity，thus achieving better clinical efficacy.

Objective:To analysis the risk factors and safety of administration of norepinephrine (NE) via peripheral vein line (PVL) in patients with septic shock.Methods:A single-center retrospective study was conducted. According to the Lanzhou University Second Hospital information system (HIS) and nursing adverse events report cards, patients with septic shock administrated with NE via PVL to correct the hypotension from January 1st 2015 to December 31st, 2019 were enrolled. The patients' general information, placement location of peripheral venous catheter and venousneedle type, characteristics of NE usage and patient general condition when extravasation occurred were collected. The univariate analysis and Logistic regression were used to analyze risk factors associated with extravasation. Also, the receiver operator characteristic curve (ROC curve) was drawn, and the predictive value of risk factors for extravasation was analyzed.Results:A total of 1 022 cases with NE were enrolled. After a preliminary screening, a total of 910 cases with NE were used to correct low blood pressure, including 116 cases of peripheral venous infusion. The average age was (52.91±18.69) years old, with majority of female (77 cases, 66.4%). Basic diseases were mainly chronic obstructive pulmonary disease (COPD, 100 cases, 86.2%), followed by hypertension(91 cases, 78.4%), coronary heart disease (87 cases, 75.0%), type 2 diabetes (74 cases, 63.8%) respectively, the primary disease was septic shock in 109 cases (94.0%). A total of 147 peripheral venous catheters were inserted, and the most common site of puncture was the forearm [78.9% (116/147)], followed by the hand [12.2% (18/147)] and the median cubital vein [8.8% (13/147)]. 89.9% of the needles were 20 G in diameter, and 75 cases (64.7%) were converted to central venous catheters (CVC) during subsequent treatment due to continuous infusion of NE. Six patients (5.2%) had extravasation, the median time of extravasation was 29 (23-39) hours, and the median time of NE was 23 (11-53) hours, including 2 patients with an infusion concentration of 60 mg/L and 4 patients with an infusion concentration of 120 mg/L.The infusion speed was 0.5-1.0 μg·kg -1·min -1, and the average speed of infusion was (0.75±0.04) μg·kg -1·min -1 when extravasation. Univariate and binary Logistic regression analysis showed that the risk factors related to the occurrence of extravasation included: ① patient factors: the presence of basic diseases, hypertension [odds ratio ( OR) = 3.11, 95% confidence interval (95% CI) was 3.09-3.12, P = 0.001] and edema ( OR = 1.79, 95% CI was 1.32-2.99, P = 0.032). ② Factors of infusion fluid itself: long-term (> 24 hours) infusion ( OR = 2.91, 95% CI was 1.04-5.96, P = 0.040), infusion concentration > 60 mg/L ( OR = 1.88, 95% CI was 1.32-3.99, P = 0.024), infusion speed > 0.3 μg·kg -1·min -1 ( OR = 2.43, 95% CI was 2.38-2.51, P = 0.029) and diameter of needles < 20 G ( OR = 3.11, 95% CI was 3.09-3.22, P = 0.033).③ Medical personnel factors: lack of observation and assessment ( OR = 1.09, 95% CI was 1.03-6.77, P = 0.043). The ROC curve analysis showed that: edema, long-term infusion (> 24 hours), infusion rate > 0.3 μg·kg -1·min -1and diameter of needles < 20 G had a certain predictive value for extravasation of NE through peripheral venous infusion in patients with septic shock, the area under ROC curve (AUC) was 0.610, 0.762, 0.672, 0.629, 95% CI was 0.508-0.713, 0.675-0.849, 0.571-0.772, 0.525-0.732, and P values were 0.044, 0.000, 0.002, 0.019, respectively. Conclusions:Hypertension, edema, long-term infusion (> 24 hours), infusion concentration > 60 mg/L, infusion speed > 0.3 μg·kg -1·min -1, diameter of needle < 20 G, and lack of observation and evaluation by medical staff regularly were risk factors affecting the safety of peripheral intravenous NE in patients with septic shock. Peripheral NE should be avoided in the presence of the above risk factors.

Objective:To investigate the relationship between blood lipid level and low birth weight infants in late pregnancy.Methods:Data of 303 low birth weight newborns delivered in ShengJing Hospital affiliated to China Medical University were collected from January 2018 to February 2020, and 303 cases of full-term normal birth weight infants delivered in our hospital during the same period (birth weight 2500 ~ 3999 g) for retrospective study.The general situation of puerpera was analyzed, including age, gestational age, times of pregnancy, times of labor, weight growth during pregnancy, pre pregnancy body mass index, and blood lipid indexes of puerpera within one week before termination of pregnancy, including triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A, apolipoprotein B.Results:The normal birth weight group was (31.60±3.90) years old, the weight gain during pregnancy was (16.29±5.31) kg, and the triglyceride levels was(3.21±1.33) mmol/L.The low birth weight group was (30.30±4.65) years old, the weight gain during pregnancy was (14.45±8.08) kg, and the triglyceride level was(2.88±1.37) mmol/L, and there were differences between groups( P<0.01). In the low term birth weight group, birth weight was negatively correlated with maternal age ( r=-0.24, P=0.01), positively correlated with gestational age ( r=0.24, P=0.02), and negatively correlated with pregnancy weight gain ( r=-0.26, P<0.01), and was positively correlated with triglyceride ( r=0.15, P=0.01) and total cholesterol ( r=0.20, P<0.01). Conclusion:The incidence of full-term low birth weight infants is closely related to the blood lipid level, age, gestational age at delivery and the growth of body weight during pregnancy.

Objective:To analyze the clinical efficacy of hyperbaric oxygen (HBO) combined with atorvastatin on patients with coronary heart disease and its effects on the changes of hemorheological indexes.Methods:A total of 150 patients with coronary heart disease admitted to the Department of Cardiology of Linyi Central Hospital from December 2016 to December 2018 were included into a retrospective analysis, who were randomly divided into the combination group and the control group, with 75 cases each. The control group was treated with atorvastatin on the basis of routine treatment, and the combination group was treated with HBO on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared after the treatment, and the changes of vascular inflammatory factors, D-dimer, and hemorheological indexes were compared before and after treatment.Results:After HBO combined with atorvastatin treatment, the total clinical effective rate of the combination group was 93.33%, which was significantly higher than that of the control group (82.67%) ( χ2=4.040, P<0.05); after 4 courses of treatment, the levels of hs-CRP, Lp-PLA2, LDL-C, and D-dimer in the two groups were significantly lower than those before treatment ( P<0.05), and those in the combination group were significantly lower than those in the control group ( P<0.05); after the treatment, the hemorheological indexes, i. e. whole blood high shear viscosity, whole blood middle shear viscosity, whole blood low shear viscosity, plasma viscosity, and fibrinogen, in the two groups were statistically significant lower than those before treatment ( P<0.05), and those in the combination group were significantly lower than those in the control group ( P<0.05). Conclusion:HBO combined with atorvastatin has a significant clinical effect in the treatment of coronary heart disease, which can significantly reduce the inflammatory reaction of blood vessels, and improve the hemorheological indexes.

Objective:To analyze the clinical efficacy of hyperbaric oxygen (HBO) combined with atorvastatin on patients with coronary heart disease and its effects on the changes of hemorheological indexes.Methods:A total of 150 patients with coronary heart disease admitted to the Department of Cardiology of Linyi Central Hospital from December 2016 to December 2018 were included into a retrospective analysis, who were randomly divided into the combination group and the control group, with 75 cases each. The control group was treated with atorvastatin on the basis of routine treatment, and the combination group was treated with HBO on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared after the treatment, and the changes of vascular inflammatory factors, D-dimer, and hemorheological indexes were compared before and after treatment.Results:After HBO combined with atorvastatin treatment, the total clinical effective rate of the combination group was 93.33%, which was significantly higher than that of the control group (82.67%) ( χ2=4.040, P<0.05); after 4 courses of treatment, the levels of hs-CRP, Lp-PLA2, LDL-C, and D-dimer in the two groups were significantly lower than those before treatment ( P<0.05), and those in the combination group were significantly lower than those in the control group ( P<0.05); after the treatment, the hemorheological indexes, i. e. whole blood high shear viscosity, whole blood middle shear viscosity, whole blood low shear viscosity, plasma viscosity, and fibrinogen, in the two groups were statistically significant lower than those before treatment ( P<0.05), and those in the combination group were significantly lower than those in the control group ( P<0.05). Conclusion:HBO combined with atorvastatin has a significant clinical effect in the treatment of coronary heart disease, which can significantly reduce the inflammatory reaction of blood vessels, and improve the hemorheological indexes.