Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Objective To construct intrauterine adhesion (IUA) mouse models induced by two different concentrations of ethanol injury, compare the phenotypes, and optimize a more stable IUA modeling method. Methods Twenty 8-week-old female C57BL/6N mice were randomly divided into two groups: the 95% ethanol injury group and the 50% ethanol injury group. Using a self-control method, the left uterine horn was infused with ethanol to establish the IUA model, while the right uterine horn was infused with saline as the sham operation. Five mice from each group were euthanized on day 7 and 15 after modeling, and uterine tissues were collected. Hematoxylin-eosin (HE) staining was used to observe the endometrial pathology, and Masson staining was used to assess the degree of endometrial fibrosis. Quantitative real-time PCR was employed to detect the expression levels of fibrosis markers and pro-inflammatory factors in the uterine tissues. Results Compared to the sham operation, these two ethanol injury led to a significant reduction in elasticity of the uterus, an increase in inflammatory infiltration, and a marked increase in the degree of fibrosis on day 7 after modeling (P<0.05). The 95% ethanol injury group showed a significant decrease in endometrial thickness (P<0.05), whereas no significant change was observed in the 50% ethanol injury group when compared to the sham operation (P>0.05). The expression levels of fibrotic marker molecules collagen type Ⅳ alpha 1 chain (Col4A1), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly elevated in the 50% ethanol injury group when compared to the sham operation (P<0.05), although there was an increasing trend of the same markers in the 95% ethanol injury group, the differences were not statistically significant (P>0.05). On day 15 after modeling, the histopathological changes in both ethanol injury groups were not significant when compared to the sham operation, the expression levels of Col4A1, TGF-β, TNF-α and IL-1β remained significantly higher in the 50% ethanol injury group (P<0.05), while only IL-1β was significantly elevated in the 95% ethanol injury group (P<0.05). Conclusion Uterine infusion with 95% ethanol results in more marked histopathological changes in the IUA mouse model compared to the 50% ethanol injury group. The 95% ethanol injury model is suitable for histopathological studies. However, the 50% ethanol injury group shows higher expression levels of fibrosis markers and pro-inflammatory factors compared to the 95% ethanol injury group, suggesting that the 50% ethanol injury model is more suitable for molecular pathological study.

Lattice strain ruthenium nanoparticles uniformly and stably supported on nitrogen-modified carbon nanosheets(RuNPs/NC)were prepared via simple wet-chemical and subsequent pyrolysis method.The nitrogen doped NC could effectively improve their uniform dispersion and lattice compression of RuNPs.Through changing the pyrolysis temperature,the nitrogen content,types and degree of lattice strain of RuNPs could be effectively tuned,which could be used to adjust and control their peroxidase-like activity.The as-prepared RuNPs/NC-900 exhibited highest peroxidase-like activity,and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine(TMB)to produce a blue product with the maximum absorption at 652 nm in the presence of H2O2.The steady-state kinetic analysis indicated that the reaction catalyzed by RuNPs/NC followed the Michaelis-Menten kinetic model.Tannic acid(TA),gallic acid(GA)and ascorbic acid(AA)could effectively inhibit the RuNPs/NC-H2O2-triggered chromogenic reaction of TMB,resulting in color fading and decrease in absorbance.Based on this,a sensitive and accurate system was constructed for detection of TA,GA and AA.The detection limits(3σ/S)for TA,GA and AA were 0.014,0.014 and 0.29 μmol/L,respectively.This study not only developed a colorimetric sensing method based on RuNPs/NC nanozyme but also offered a new approach for the sensitive detection of antioxidants in food.

Objective:We applied a hypoxia-induced model of human fetal retinal microvascular endothelial cell (RMEC) to study the effect of carbonic anhydrase 9 (CA9) on cell proliferation.Methods:The eyeballs of spontaneously aborted fetuses in Guangdong Women and Children's Hospital were obtained, and the retinas were isolated. RMEC was obtained by trypsin and collagenase two-step enzyme digestion, and endothelial cells were identified by CD34. The fetal RMEC and the purchased adult RMEC were cultured in normoxic and hypoxic incubators (1%O 2+5%CO 2+94%N 2), and the expression of CA9 was detected by qPCR and Western blot. After knocking down the CA9 by small interference RNA technique, the cell proliferation was detected by CCK-8 method, and the cell viability was detected by CCK-8 after adding CA9 inhibitor U-104. Results:The primary RMEC was extracted successfully. Immunofluorescence staining showed the percentage of CD34 positive cells in the third-generation cells was nearly 100%. The expression of CA9 mRNA in immature fetus and adult RMEC under hypoxia culture was higher than that under normoxic culture (fetal 1% O 2 group vs. fetal 21% O 2 group: 67.80±10.31 vs. 1.00±0.04, P<0.001; adult 1% O 2 group vs. adult 21% O 2 group: 1.72±0.22 vs. 1.00±0.02, P=0.014). Western blot analysis showed significantly increased expression of CA9 in the fetal RMEC exposed to hypoxia, which aligned with the expression of CA9 mRNA. When fetal RMEC was transfected with siCA9 20 nM, the knockdown rate of CA9 was 95% ( P<0.001). CCK-8 assay showed significantly lower proliferation of fetal RMEC cells in siCA9 group compared to siNC group (0.57±0.05 vs. 0.90±0.03, P<0.001), which was reflected by the OD value. With the addition of 100 μM CA9 inhibitor U-104, the viability of fetal RMEC in the treated groupwas significantly lower than that in the untreated group (99.16%±3.82% vs. 119.10% ±1.72%, P=0.002). Conclusions:The expression of CA9 differed between adult and preterm fetus in our hypoxia-induced RMEC model. Inhibiting CA9 can inhibit the proliferation of retinal microvascular endothelial cells of preterm fetus.

ObjectiveOur recent study has demonstrated that extracellular acidification promotes lipid accumulation in macrophages via the activation of acid sensing ion channel 1 (ASIC1), but the underlying mechanism remains unclear. This study aims to explore the effect of extracellular acidification on macrophage lipophagy and the underlying mechanism. MethodsRAW264.7 macrophages were incubated with 25 mg/Lox-LDL in a pH 6.5 culture medium for 24 h to build macrophage-derived foam cell models induced by extracellular acidification. Then, RAW264.7 macrophages were cultured in the acidic medium of pH 6.5 with or without PcTx-1 (ASIC1 specific blocker, 10 μg/L) or Nec-1 (RIP1 specific inhibitor, 20 μmol/L) for 24 h, intracellular lipid accumulation was observed by oil red O staining. The expressions of total ASIC1, plasma membrane ASIC1, RIP1, p-RIP1 Ser166, TFEB, p-TFEB Ser142, LC3 and p62 were measured by Western blot. The co-localization of lipids (indicated by Bodipy) with LC3II (autophagosomes) and LAMP1 (lysosomes) was analyzed by a confocal laser scanning microscopy, respectively. Morphological changes of lipophagy in the cells were observed by using transmission electron microscopy. ABCA1-mediated cholesterol efflux was determined by cholesterol fluorescence kits. ResultsCompared with pH 7.4+ox-LDL group, the intracellular lipid accumulation in the pH 6.5+ox-LDL group was significantly increased. Meanwhile, the expressions of plasma membrane ASIC1, p-RIP1 Ser166, p-TFEB Ser142, and p62 proteins were elevated significantly, while LC3II protein level and LC3II/LC3I ratio were decreased. Accordingly, compared with pH 7.4+ox-LDL group, the macrophage lipophagy of the pH 6.5+ox-LDL group was inhibited as indicated by the decreased localization of lipid droplets with LC3 and LAMP1, a decrease in the number of lipophagosomes as well as an increase in lipid droplets. Furthermore, ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from the macrophages of pH 6.5+ox-LDL group reduced dramatically. However, these above effects of extracellular acidification on RAW264.7 macrophages were abolished by PcTx-1 and Nec-1, respectively. ConclusionThese findings suggest extracellular acidification promotes the phosphorylation of TFEB at Ser142 via activating ASIC1/RIP1 pathway, thereby impeding lipophagy in RAW 264.7 macrophages, and that ASIC1 may be a new potential target for preventing aberrant lipid accumulation diseases including atherosclerosis.

Objective To compare the efficacy of 30 g·L-1diquafosol sodium eye drops and 0.5 g·L-1 cyclospo-rine eye drops in patients with dry eye after femtosecond laser small incision lenticule extraction(SMILE).Methods A total of 37 patients(74 eyes)undergoing SMILE in Xi'an Fourth Hospital from January to February 2024 were selected as the subjects.Patients were randomly divided into the cyclosporine group(11 patients),diquafosol sodium group(16 pa-tients),and control group(10 patients)through a random number table method.There were no significant differences in the age and gender of patients in the three groups(both P＞0.05).Patients in the cyclosporine group were treated with 0.5 g·L-1 cyclosporine eye drops,twice a day,1 drop each time,for 3 months.Patients in the diquafosol sodium group were treated with 30 g·L-1 diquafosol sodium eye drops,6 times a day,1 drop each time,for 3 months.Patients in the control group were treated with sodium hyaluronate eye drops,3 times a day,1 drop each time,for 3 months,and the fre-quency of administration could be adjusted according to clinical symptoms.The visual acuity,intraocular pressure,redness scan(R-Scan),Schirmer tear test(SIT),non-invasive break-up time(NIBUT)and ocular surface disease index(OSDI)questionnaire scores were measured in all patients at 1 month and 3 months after the operation.SPSS 22.0 statistical soft-ware was used for data analysis,and visual acuity,intraocular pressure,R-Scan,SIT,NIBUT and OSDI scores were com-pared among the three groups before,1 month and 3 months after the operation.Results In the cyclosporine group,in-traocular pressures of patients at 1 month and 3 months postoperatively were significantly lower than the preoperative level;the NIBUT was significantly prolonged at 3 months after operation compared with the preoperative level;OSDI scores were significantly elevated at both 1 month and 3 months postoperatively compared with the preoperative level(all P＜0.05).In the diquafosol sodium group,intraocular pressure at 1 month and 3 months postoperatively was significantly lower than the preoperative level;the SIT at 3 months after the operation was lower than that before operation;OSDI was higher 1 month after operation than pre-operation and 3 months after operation(all P＜0.05).In the control group,intraocular pressure at 1 month and 3 months postoperatively was significantly lower than the preoperative level;the naked eye visual acuity 3 months after operation was better than the best corrected visual acuity before operation(all P＜0.05).There was no signif-icant difference in visual acuity,intraocular pressure and R-Scan among the three groups 1 month and 3 months after opera-tion(all P＞0.05).One month after the operation,SIT and NIBUT in the control group were higher than those in the cy-closporine group and diquafosol sodium group(all P＜0.05);the OSDI of diquafosol sodium group was higher than that of the cyclosporine group(P＜0.05).Conclusion Both cyclosporine eye drops and diquafosol sodium eye drops can re-lieve ocular surface discomfort after SMILE and cyclosporine eye drops are more helpful to improve tear film stability.

Objective:To analyze the relevant factors affecting postnatal glucose metabolism in pregnant women with gestational diabetes and construct a nomogram prediction model.Methods:Using a retrospective study method, 210 cases of gestational diabetes patients admitted to Danyang People′s Hospital from March 2019 to November 2021 were selected as the study subjects, and they were divided into 125 cases of normal group and 85 cases of abnormal group according to the postnatal glucose metabolism. The predictive value was analyzed using the subject work characteristics (ROC) curve experiment; the risk factors affecting abnormal postpartum glucose metabolism in pregnant women with gestational diabetes mellitus were analyzed using Logistic regression experiment; and the clinical efficacy of the column-line diagram model was verified using internal data.Results:There was no statistically significant difference between the two groups when comparing the general information such as age ( P>0.05); compared with the normal group, the abnormal group had higher values of total cholesterol (TG), postprandial 2 h blood glucose (OGTT 2 h), glycosylated hemoglobin, and pre-pregnancy body mass index (BMI): (4.23 ± 1.35) mmol/L vs. (3.65 ± 1.50) mmol/L, (9.36 ± 1.25) mmol/L vs. (8.20 ± 1.51) mmol/L, (8.31 ± 2.96)% vs. (6.73 ± 2.23)%, (24.96 ± 4.21) kg/m 2 vs. (23.20 ± 3.25) kg/m 2, and those with a family history of diabetes mellitus were higher: 47.06%(40/85) vs. 20.80%(26/125), there were statistical differences ( P<0.05); the area under the curve (AUC) of TG, OGTT 2 h, glycated hemoglobin, and pre-pregnancy BMI were 0.605, 0.720, 0.670, and 0.616, with optimal cut off values of 4.65 mmol/L, 8.33 mmol/L, 8.06%, and 25.27 kg/m 2; TG (>4.65 mmol/L), OGTT 2 h (>8.33 mmol/L), glycated hemoglobin (>8.06%), and preconception BMI (>25.27 kg/m 2), and family history of diabetes mellitus (yes) were risk factors for abnormal glucose metabolism in pregnant women ( P<0.05); the C-index of the risk of postpartum glucose metabolism in pregnant women with gestational diabetes mellitus predicted by the column chart model was 0.750 (95% CI 0.672 - 0.864). The model predicted that the threshold of the risk of postnatal glucose metabolism in pregnant women with gestational diabetes mellitus was >0.07. Conclusions:TG (>4.65 mmol/L ), OGTT 2 h (>8.33 mmol/L ), glycated haemoglobin (>8.06%), pre-pregnancy BMI (>25.27 kg/m 2), and family history of diabetes (yes) are risk factors for abnormal glucose metabolism in pregnant women, and the model constructed based on the variables have good predictive power.

Objective To investigate the evaluation of the nursing staff of the tertiary hospitals in Shenzhen City on the status quo of the nursing clinical support system,and to analyze its influencing factors so as to provide reference and basis for perfecting the nursing clinical support system.Methods The nursing staffs in 16 hospitals of 8 districts of Shenzhen City from December 2022 to January 2023 were selected as the survey subjects,and the general data questionnaire and the nursing clinical support system questionnaire were used for conducting the survey.Results A total of 572 questionnaires were collected,and 520 questionnaires were valid,with an effective recovery rate of 90.9％.The scores of each dimension in the nursing clinical sup-port system scale were(1.87±0.81)points for equipment and appliance support,(1.07±0.62)points for aux-iliary staff support,(1.91±0.80)points for the logistics departments support,(0.88±0.67)points for the auxiliary departments support.The results of univariate analysis showed that there were statistical differences in the equipment and appliance support scores among the nurses with different ages,different professional ti-tles and different education levels(P＜0.01);the scores of 4 dimensions had statistical differences among the nursing staffs with different departments(P＜0.01).All factors had statistically significant differences in the dimension of auxiliary department support(P＜0.05).Conclusion The popularity degree of nursing clinical support system in tertiary hospitals in Shenzhen City is high,and equipment and appliance show the character-istics of advancement and diversity.The hospital managers should strengthen the force of nursing clinical sup-port system and reduce the nursing staff to engage in non-nursing work.

AIM:To investigate the impact and regulatory mechanisms of zinc finger protein 36-like protein 1(ZFP36L1)on pancreatic carcinoma cell growth.METHODS:The ZFP36L1 expression in pancreatic carcinoma and its correlation with patient prognosis were analyzed using online databases UALCAN and GEPIA.Western blot was utilized to detect ZFP36L1 protein expression in pancreatic ductal cells(HPNE)and three different pancreatic carcinoma cell lines.CCK-8 and cell colony formation assays were performed to evaluate the effects of ZFP36L1 on pancreatic cancer cell prolif-eration.Wound healing and Transwell assays were used to assess the impact of ZFP36L1 expression changes on pancreatic carcinoma cell migration and invasion.Flow cytometry experiments were used to analyze the effect of ZFP36L1 on the pan-creatic carcinoma cell cycle process.Bioinformatics analysis was conducted to predict potential ZFP36L1 interacting pro-teins.Co-immunoprecipitation experiments were carried out to confirm the interaction between ZFP36L1 and mitogen-acti-vated protein kinase 14(MAPK14).Rescue experiments were performed to assess the function of MAPK14 in ZFP36L1-regulated pancreatic carcinoma cell growth.RESULTS:(1)ZFP36L1 is highly expressed in pancreatic carcinoma and is positively correlated with poor prognosis in pancreatic carcinoma patients.Compared to HPNE,ZFP36L1 is highly ex-pressed in MIA PaCa-2 and ASPC-1 cells,but relatively low in PANC-1 cells.(2)ZFP36L1 overexpression significantly increased the cell viability,colony formation,migration,and invasion abilities of PANC-1 and MIA PaCa-2 cells,while siRNA interference of ZFP36L1 led to opposite results.(3)ZFP36L1 promotes the entry of pancreatic carcinoma cells into the S phase of the cell cycle.(4)ZFP36L1 interacts with MAPK14 to regulate pancreatic cancer cell growth.MAPK14 overexpression reversed the cell viability and migration abilities of pancreatic carcinoma cells overexpressing ZFP36L1.Furthermore,it also decreased the cell viability and migration abilities of pancreatic carcinoma cells with ZFP36L1 inter-ference.CONCLUSION:ZFP36L1 is a potential oncogene in pancreatic carcinoma growth and may regulate pancreatic carcinoma cell growth through cell cycle modulation and interaction with MAPK14.

Aim To analyze the risk factor of the cardiac rupture(CR)in patients with acute ST-segment eleva-tion myocardial infarction(STEMI).Based on this,the nomogram model of acute STEMI patients with CR was estab-lished.Methods Through Ningxia Medical University General Hospital's big data research platform and hospital in-formation system retrieval,5 412 patients with acute STEMI from January 2015 to December 2019 were continuously includ-ed in the study,of which 91 patients with CR were included as CR group;5 321 patients non-combined with CR were in-cluded as non-CR group.LASSO regression,univariate and multivariate Logistic regression were used to analyze the risk factors of CR in patients with acute STEMI,and the CR nomogram predictive model was established.The nomogram mod-el was validated and evaluated by using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test and clinical decision curve analysis(DCA).Results LASSO regression results showed that age,female,hypertension history,first medical contact time,shock index,Killip grade,white blood cell count,d-dimer,lactic acid,anterior myocardial in-farction,β-blocker administration within 24 hours,angiotensin converting enzyme inhibitor/angiotensin receptor antagonist(ACEI/ARB)administration within 24 hours,emergency percutaneous coronary intervention(PCI)were 13 risk factors of CR(P＜0.05).The screened 13 risk factors were analyzed by univariate and multivariate Logistic regression,the results suggested that age,Killip grade,first medical contact time,white blood cell count,not undergoing emergency PCI and not taking ACEI/ARB drugs within 24 hours were the risk factors of CR in patients with acute STEMI.The acute STEMI with CR nomogram model was established according to the above 6 risk variables.The area under the ROC curve before and after the internal verification of the nomogram model was 0.946(95％CI:0.927～0.961),0.947(95％CI:0.927～0.959),and the sensitivity was 0.957 and 0.904,respectively,the specificity was 0.858 and 0.876,respectively,which indicated that the model had good discrimination degree.The Hosmer-Lemeshow test showed that the deviation between the predicted value and the observed value was not statistically significant(x2=12.70,P=0.122),indicating that the no-mogram model had a good calibration.The DCA curve indicated that the predictive probability threshold of the model was from 0.00 to 0.40,and the clinical net benefit was the highest,indicating that the model had good clinical efficacy.Conclusion The nomogram model established in this study has better distinction,calibration and clinical effectiveness.It can effectively predict the probability of acute STEMI with CR,and provide some help for clinical diagnosis and treat-ment,so as to reduce the incidence of CR.