Objective:To investigate the effect of hypoxia on the expression of forkhead box P3 (FOXP3) in human oral squamous cell carcinoma (OSCC) cells,and to clarify its possible epigenetic mechanism.Methods:Two kinds of OSCC cell lines,FaDu and OECM-1,were cultured under normoxic or hypoxic conditions for 18 h.The relative expression levels of FOXP3 mRNA and protein in the cells were detected by Real-time RT-PCR and Western blotting method.The histone modification levels on the FOXP3 gene promoter,including acetylation of histone 3 lysine 4 (H3K4ac),trimethylation of histone 3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3),were analyzed by Chromatin Immunocipitation (ChIP) and quantitative PCR (ChIP-qPCR).The relative expression levels of histone deacetylase 3 (HDAC3) mRNA and inhibitory rates of FOXP3 mRNA expression in the HDAC3-knockdown FaDu cells were investigated by Real-time qPCR and ChIP-qPCR.Results:Compared with normoxic condition,the relative expression levels of FOXP3 mRNA in FaDu and OECM-1 cells under hypoxic condition were decreased by 65.6% and 75.7% (P<0.01).The Western blotting results indicated that compared with normoxic condition,the expression levels of FOXP3 protein in FaDu and OECM-1 cells under hypoxic condition were decreased.The ChIP experiment results showed that compared with normoxic condition,the levels of H3K4ac and H3K4me3 on FOXP3 gene promoter in FaDu cells were decreased under hypoxic condition (P<0.01),while the H3K27me3 level was not changed.In HDAC3-knockdown FaDu cells,compared with control cells,the inhibitory rates of the expressions of H3K4ac and H3K4me3 on FOXP3 gene promoter under hypoxia condition were decreased (P<0.05),so did expressions the FOXP3 mRNA expression (P<0.05).Conclusion:Hypoxia could suppress the expression of FOXP3 by HDAC3-mediated down-regulation of H3K4ac on FOXP3 gene promoter in the human OSCC cells.

BACKGROUND:The traditional surgical treatment for stromal corneal dystrophy is penetrating keratoplasty.In recent years,more and more doctors are considering using deep lamellar keratoplasty to treat stromal corneal dystrophy.Few studies comparing penetrating keratoplasty and deep lamellar keratoplasty for stromal corneal dystrophy have been reported in China. OBJECTIVE:To compare the clinical efficacy of deep lamellar keratoplasty and penetrating keratoplasty in the treatment of stromal corneal dystrophy. METHODS:Fifty-seven patients(57 eyes)diagnosed with stromal corneal dystrophy and admitted at the General Hospital of Northern Theater Command from January 2000 to January 2018 were selected,including 18 males and 39 females,aged(52.9±20.0)years.They were divided into two groups based on the surgical procedure:21 cases(21 eyes)in the deep lamellar keratoplasty group and 36 cases(36 eyes)in the penetrating keratoplasty group.A 12-month follow-up was conducted to observe the best-corrected visual acuity,corneal endothelial cell density,corneal grafttransparency,intraoperative and postoperative complications,and recurrence of the original disease. RESULTS AND CONCLUSION:Visual acuity at 1,3,6,and 12 months postoperatively was higher than preoperatively in both groups(P<0.05).The postoperative best-corrected visual acuity between the two groups showed no significant difference(P>0.05).With the prolongation of postoperative time,the corneal endothelial cell density gradually decreased in the two groups,and the annual loss rate of corneal endothelial cell density in the penetrating keratoplasty group was higher than that of the deep lamellar keratoplasty group at 6 and 12 months postoperatively(P<0.05),while there was no significant difference in corneal grafttransparency between the two groups at 12 months postoperatively(P>0.05).There were six cases of complications in the deep lamellar keratoplasty group and 14 cases of complications in the penetrating keratoplasty group.There was no recurrence in 57 cases within 12 months after surgery,and the difference in recurrence rates between the two groups at 5 years after surgery was not significant(P>0.05).The graftsurvival rates at 5 years after surgery in the penetrating keratoplasty group and the deep lamellar keratoplasty group were 83%and 86%,respectively,and there was no significant difference between the two groups(P>0.05).To conclude,deep lamellar keratoplasty could be considered as an alternative to penetrating keratoplasty in the treatment of stromal corneal dystrophy.

Objective To comprehend the sense of competence and depression status for neonatal father and explore the relationship between them in order to provide evidence for the improvement of psychological and physical health. Methods A total of 180 3 days neonatal father had been chosen by convenience sampling method in 5 three-level hospitals in Xi′an. We utilized Edinburgh Postnatal Depression Scale and the Chinese version of the Parenting Sense of Competence Scale ( PSCS) to survey neonatal father by questionnaire and analyzed neonatal father′s sense of competence and depression by Spearman correlation analysis. Results The average score of neonatal father′s PSCS acquired (69. 74 ± 8. 40) while there were 35 (21. 08%) father felt depression. Parenting sense of competence had negative correlation with postpartum depression (r= -0. 510,-0. 507,-0. 326,respectively;P<0. 01). Conclusions The depression of neonatal father is one issue neglected which could impact on parenting sense of competence.

Objective To investigate the target blood pressure level of restrictive fluid resuscitation in patients with traumatic hemorrhagic shock. Methods Sixty patients with traumatic hemorrhagic shock admitted to the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2018 were enrolled. All patients were resuscitated with sodium acetate ringer solution after admission. According to the difference of mean arterial pressure (MAP) target, the patients were divided into low MAP (60 mmHg ≤ MAP < 65 mmHg, 1 mmHg = 0.133 kPa), middle MAP (65 mmHg ≤ MAP < 70 mmHg) and high MAP (70 mmHg ≤ MAP < 75 mmHg) groups by random number table using the admission order with 20 patients in each group. Those who failed to reach the target MAP after 30-minute resuscitation were excluded and supplementary cases were deferred. The restrictive fluid resuscitation phase was divided into three phases: before fluid resuscitation, liquid resuscitation for 30 minutes and 60 minutes. The most suitable resuscitation blood pressure level was further speculated by monitoring the inflammatory markers and hemodynamics in different periods in each group of patients. Pearson correlation analysis was used to detect the correlation of variables. Results Before fluid resuscitation, there was no significant difference in hemodynamics or expressions of serum cytokines among the three groups. Three groups of patients were resuscitated for 30 minutes to achieve the target blood pressure level and maintain 30 minutes. With the prolongation of fluid resuscitation time, the central venous pressure (CVP), cardiac output (CO) and cardiac index (CI) were increased slowly in the three groups, and reached a steady state at about 30 minutes after resuscitation, especially in the high MAP group and the middle MAP group. The expressions of serum inflammatory factors in the three groups were gradually increased with the prolongation of fluid resuscitation time. Compared with the low MAP group and the high MAP group, after 30 minutes of resuscitation the middle MAP group was superior to the other two groups in inhibiting the expressions of pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and promoting anti-inflammatory factors IL-10 [TNF-α mRNA (2-ΔΔCt):0.21±0.13 vs. 0.69±0.34, 0.57±0.35; IL-6 mRNA (2-ΔΔCt): 0.35±0.31 vs. 0.72±0.39, 0.59±0.42; IL-10 mRNA (2-ΔΔCt): 1.25±0.81 vs. 0.61±0.46, 0.82±0.53; all P < 0.05], but there was no significant difference in promoting the expression of IL-4 mRNA among three groups. At 60 minutes of resuscitation, compared with the low MAP group and the high MAP group, the middle MAP group could significantly inhibit the expressions of TNF-α, IL-6 and promote IL-10 [TNF-α mRNA (2-ΔΔCt): 0.72±0.35 vs. 1.05±0.54, 1.03±0.49; IL-6 mRNA (2-ΔΔCt): 0.57±0.50 vs. 1.27±0.72, 1.01±0.64; IL-10 mRNA (2-ΔΔCt): 1.41±0.90 vs. 0.81±0.48, 0.94±0.61; all P < 0.05]. Compared with the high MAP group, the middle MAP group had significant differences in promoting the expression of IL-4 mRNA (2-ΔΔCt: 1.32±0.62 vs. 0.91±0.60, P < 0.05). There was no significant difference in serum cytokine expressions at different time points of resuscitation between the low MAP group and the high MAP group (all P > 0.05). Correlation analysis showed that there was a strong linear correlation between MAP and mRNA expressions of TNF-α, IL-6, IL-10 in the middle MAP group (r value was 0.766, 0.719, 0.692, respectively, all P < 0.01), but had no correlation with IL-4 (r = 0.361, P = 0.059). Fitting linear regression analysis showed an increase in 1 mmHg per MAP, the expression of TNF-α mRNA increased by 0.027 [95% confidence interval (95%CI) = 0.023-0.031, P < 0.001], IL-6 mRNA increased by 0.021 (95%CI = 0.017-0.024, P < 0.001), and IL-10 mRNA increased by 0.049 (95%CI = 0.041-0.058, P < 0.001). Conclusions When patients with traumatic hemorrhagic shock received restrict fluid resuscitation at MAP of 65-70 mmHg, the effect of reducing systemic inflammatory response and improving hemodynamics is better than the target MAP at 60-65 mmHg or 70-75 mmHg. It is suggested that 65-70 mmHg may be an ideal target MAP level for restrictive fluid resuscitation.

Objective:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR), and to explore the risk factors leading to poor prognosis.Methods:The clinical data of 95 patients with ECPR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023 were retrospectively analyzed. According to the survival status at the time of discharge, the patients were divided into the survival group and death group. The difference of clinical data between the two groups was compared to explore the risk factors related to death and poor prognosis. Risk factors associated with death were identified by Binary Logistic regression analysis. Results:A total of 95 patients with ECPR were included in this study, 62 (65.3%) died and 33 (34.7%) survived at discharge. Patients in the death group had longer low blood flow time [40 (30, 52.5) min vs. 30 (24.5, 40) min ] and total cardiac arrest time[40 (30, 52.5) min vs. 30(24.5, 40) min], shorter total hospital stay [3 (2, 7.25) d vs. 19 (13.5, 31) d] and extracorporeal membrane oxygenation (ECMO) assisted time [26.5 (17, 50) h vs. 62 (44, 80.5) h], and more IHCA patients (56.5% vs. 33.3%) and less had spontaneous rhythm recovery before ECMO (37.1% vs. 84.8%). Initial lactate value [(14.008 ± 5.188) mmol/L vs.(11.23 ± 4.718) mmol/L], APACHEⅡ score [(30.10 ± 7.45) vs. (25.88 ± 7.68)] and SOFA score [12 (10.75, 16) vs. 10 (9.5, 13)] were higher ( P< 0.05). Conclusions:No spontaneous rhythm recovery before ECMO, high initial lactic acid and high SOFA score are independent risk factors for poor prognosis in ECPR patients.

Objective RY-15, a specific agonist of Sphingosine 1-phosphate Receptor 3, was synthesized for investigating the function and mechanism of S1PR3 in bacterial clearance. Methods Measure the ability of RY-15 with FITC to enter the THP-1 cell after coculture for 5 min, 10 min, 20 min, 30 min through confocal microscopy. The function of GY-5 and RY-15 in bacterial clearance was observed by gentamicin protection test. The phosphorylation level of ERK and p-ERK in THP-1 cell was detected by Western Blot after GY-5 and RY-15 stimulation for different times. Results According to confocal microscopy, RY-15 started to enter the THP-1 cell after stimulating for 10 min and the effect of entering cell was very obvious after stimulating for 30 min. Compared to GY-5 group, live bacteria in the macrophage were largely decreased in the RY-15 group( P<0.05). Conmpared to GY-5 group, the p-ERK level raised largely at different poins. Conclusions RY-15, a specific agonist of Sphingosine 1-phosphate Receptor 3, can promote bacterial clearance through entering cell and the phosphorylation level of ERK is a possible mechanism.

Objective:Explore the predictive value of the C-reactive protein to albumin ratio (CAR) and combined indicators for the prognosis of cardiac arrest (CA) patients.Methods:Retrospective analysis was conducted on patients who recovered spontaneous circulation after cardiopulmonary resuscitation (CPR) admitted to the First Affiliated Hospital of Zhengzhou University from January 2021 to May 2023. Patients were divided into survival and non-survival groups based on their status at discharge. Baseline characteristics, CPR data, and laboratory indicators were compared between the two groups. Statistically significant indicators were further analyzed using multivariate logistic regression to identify independent risk factors affecting the prognosis of CA patients. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of each independent factor and combined indicators for the prognosis of CA patients.Results:A total of 145 patients were included in the study, including 33 patients in the survival group and 112 patients in the non-survival group. There were statistically significant differences between the survival group and the non-survival group in terms of CPR duration, the dosage of vasopressor drugs used, ICU length of stay, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score at ICU admission, lactate, fibrinogen, aspartate aminotransferase, albumin, procalcitonin, C-reactive protein, CAR, myoglobin, and creatine kinase isoenzyme (all P < 0.05). Multivariate logistic regression analysis revealed that CAR and CPR duration were independent risk factors affecting the prognosis of CA patients (CAR: OR=2.372, 95% CI: 1.094~5.146, P=0.029; CPR duration: OR=1.170, 95% CI: 1.020~1.342, P=0.025). ROC curve analysis showed that the areas under the curve for CAR, CPR duration, and their combination in predicting patient prognosis were 0.792, 0.731, and 0.859, respectively. The cut-off values for CAR and CPR duration were 1.455 and 11.5 minutes, respectively. Conclusions:The CAR and CPR duration are independent risk factors affecting the prognosis of CA patients, and the predictive value is higher when both CAR and CPR duration are combined. A CAR greater than 1.455 and a CPR duration longer than 11.5 minutes suggest a poorer prognosis for the patients.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.