Ischemic stroke is a cerebrovascular disease with high incidence and disability rates. Non-coding RNAs， as important regulatory factors for gene expression， play a key role in the development and progression of ischemic stroke， but their specific mechanisms of action remain unclear. This article systematically reviews the expression characteristics and regulatory roles of microRNAs， long non-coding RNAs， and circular RNAs in ischemic stroke and reveals the pathophysiological mechanisms of non-coding RNAs in ischemic injury by regulating the processes of cell apoptosis and autophagy， inflammatory response， blood-brain barrier integrity， and neuroregeneration. In addition， non-coding RNAs have shown the potential as biomarkers for the prediction， diagnosis， and prognostic evaluation of ischemic stroke. This article also analyzes the limitations of current research and proposes future research directions， so as to provide a theoretical foundation for exploring the mechanism of action of non-coding RNAs in ischemic stroke and developing innovative diagnostic and therapeutic strategies.
Review

OBJECTIVE To explore the distribution and drug resistance trends of the main pathogens causing blood-stream infections(BSI)in neonatal intensive care unit(NICU)of Henan Province from 2014 to 2023 so as to pro-vide bases for prevention and control of hospital-associated infections in the neonates and reasonable use of antibi-otics in the whole province.METHODS The data regarding to the pathogens causing BSI in the NICU neonates and drug resistance were retrospectively collected from Jan.2014 to Dec.2023,and the statistical analysis was per-formed by SPSS 26.0 and WHONET 5.6 software.RESULTS Totally 27,984 strains of pathogens were collected from 2014 to 2023,13,547(48.41％)of which were gram-negative bacteria,and 14,437(51.59％)were gram-pos-itive bacteria.Klebsiella pneumoniae(4221 strains,15.08％),Escherichia coli(3735 strains,13.35％),Acine-tobacter baumannii(1288 strains,4.60％),Enterobacter cloacae(847 strains,3.12％)and Pseudomonas aerugi-nosa(655 strain,2.34％)were the major species of gram-negative bacteria;Staphylococcus aureus(4545 strains,16.24％),Staphylococcus epidermidis(3306 strains,11.81％),Staphylococcus haemolyticus(2048 strains,7.32％),Staphylococcus hominis(1085 strains,3.88％)and Enterococcus faecalis(946 strains,3.38％)were the predominant species of gram-positive bacteria.The drug resistant analysis indicated that the drug resistance rate of the K.pneumoniae strains to imipenem showed an upward trend during the past six years,peaking at 44.23％,and it began to decline in 2021;though the drug resistance rate of the E.coli strains to imipenem showed some fluctuations,it gener-ally presented a downward trend,peaking at 7.00％.The drug resistance rates of the K.pneumoniae strains to the third generation of cephalosporins and carbapenems were higher than those of the E.coli,and there was significant differ-ence in the antimicrobial prevalence trend between the two species of Enterobacter during the ten years(P＜0.05).CONCLUSIONS K.pneumoniae and coagulase-negative Staphylococcus are dominant among the pathogens causing BSI in the ICU neonates of the whole province,and the isolation rates of drug-resistant strains are high.It is grossly necessary for the reasonable clinical use of antibiotics to carry out the bacterial drug resistance surveillance.

Objective:To study the effects of arsenic exposure on neurological function including voluntary motor ability, anxiety, and short-term memory ability of rats, as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1 (NLGN1), glutamate receptor 2A (NR2A), and postsynaptic density protein 95 (PSD95).Methods:Forty 3-week-old male specific pathogen free (SPF) grade Wistar rats [weighing (453.97 ± 35.68) g] were selected and divided into four groups using a random number table: 0 (control group) and 2, 10, and 50 mg/L arsenic exposure groups, with 10 rats in each group. They were given deionized water and 2, 10, and 50 mg/L sodium arsenite solutions for 12 weeks, respectively. The open field experiment and Y-maze experiment were used to test the voluntary motor ability, anxiety, and short-term memory ability of rats. Nissl staining was used to observe the pathological damage of the hippocampus in the brain. Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1, NR2A, and PSD95 in the hippocampus, respectively.Results:The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group, the movement distances in the central area in the 2, 10, and 50 mg/L arsenic exposure groups were reduced compared to the control group, and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group ( P < 0.05). The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group ( P < 0.05). The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures, tightly arranged cells, appearing blue purple in color and clear visible nuclei. However, the number of Nissl bodies decreased, intercellular gaps increased, disordered arrangement increased, cytoplasmic staining was lighter, and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2, 10 and 50 mg/L arsenic exposure groups. The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1, NR2A, and PSD95 in the hippocampal tissues of the four groups ( F = 13.85, 44.94, 4.63, P < 0.05). The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group (0.65 ± 0.07, 0.69 ± 0.03 vs 1.00 ± 0.04, 0.51 ± 0.11, 0.51 ± 0.13 vs 1.00 ± 0.07, P < 0.05), and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group (0.51 ± 0.09 vs 1.00 ± 0.05, P < 0.05). Conclusion:Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1, NR2A, and PSD95.

Objective:To study the effects of arsenic exposure on neurological function including voluntary motor ability, anxiety, and short-term memory ability of rats, as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1 (NLGN1), glutamate receptor 2A (NR2A), and postsynaptic density protein 95 (PSD95).Methods:Forty 3-week-old male specific pathogen free (SPF) grade Wistar rats [weighing (453.97 ± 35.68) g] were selected and divided into four groups using a random number table: 0 (control group) and 2, 10, and 50 mg/L arsenic exposure groups, with 10 rats in each group. They were given deionized water and 2, 10, and 50 mg/L sodium arsenite solutions for 12 weeks, respectively. The open field experiment and Y-maze experiment were used to test the voluntary motor ability, anxiety, and short-term memory ability of rats. Nissl staining was used to observe the pathological damage of the hippocampus in the brain. Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1, NR2A, and PSD95 in the hippocampus, respectively.Results:The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group, the movement distances in the central area in the 2, 10, and 50 mg/L arsenic exposure groups were reduced compared to the control group, and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group ( P < 0.05). The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group ( P < 0.05). The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures, tightly arranged cells, appearing blue purple in color and clear visible nuclei. However, the number of Nissl bodies decreased, intercellular gaps increased, disordered arrangement increased, cytoplasmic staining was lighter, and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2, 10 and 50 mg/L arsenic exposure groups. The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1, NR2A, and PSD95 in the hippocampal tissues of the four groups ( F = 13.85, 44.94, 4.63, P < 0.05). The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group (0.65 ± 0.07, 0.69 ± 0.03 vs 1.00 ± 0.04, 0.51 ± 0.11, 0.51 ± 0.13 vs 1.00 ± 0.07, P < 0.05), and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group (0.51 ± 0.09 vs 1.00 ± 0.05, P < 0.05). Conclusion:Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1, NR2A, and PSD95.

OBJECTIVE To explore the distribution and drug resistance trends of the main pathogens causing blood-stream infections(BSI)in neonatal intensive care unit(NICU)of Henan Province from 2014 to 2023 so as to pro-vide bases for prevention and control of hospital-associated infections in the neonates and reasonable use of antibi-otics in the whole province.METHODS The data regarding to the pathogens causing BSI in the NICU neonates and drug resistance were retrospectively collected from Jan.2014 to Dec.2023,and the statistical analysis was per-formed by SPSS 26.0 and WHONET 5.6 software.RESULTS Totally 27,984 strains of pathogens were collected from 2014 to 2023,13,547(48.41％)of which were gram-negative bacteria,and 14,437(51.59％)were gram-pos-itive bacteria.Klebsiella pneumoniae(4221 strains,15.08％),Escherichia coli(3735 strains,13.35％),Acine-tobacter baumannii(1288 strains,4.60％),Enterobacter cloacae(847 strains,3.12％)and Pseudomonas aerugi-nosa(655 strain,2.34％)were the major species of gram-negative bacteria;Staphylococcus aureus(4545 strains,16.24％),Staphylococcus epidermidis(3306 strains,11.81％),Staphylococcus haemolyticus(2048 strains,7.32％),Staphylococcus hominis(1085 strains,3.88％)and Enterococcus faecalis(946 strains,3.38％)were the predominant species of gram-positive bacteria.The drug resistant analysis indicated that the drug resistance rate of the K.pneumoniae strains to imipenem showed an upward trend during the past six years,peaking at 44.23％,and it began to decline in 2021;though the drug resistance rate of the E.coli strains to imipenem showed some fluctuations,it gener-ally presented a downward trend,peaking at 7.00％.The drug resistance rates of the K.pneumoniae strains to the third generation of cephalosporins and carbapenems were higher than those of the E.coli,and there was significant differ-ence in the antimicrobial prevalence trend between the two species of Enterobacter during the ten years(P＜0.05).CONCLUSIONS K.pneumoniae and coagulase-negative Staphylococcus are dominant among the pathogens causing BSI in the ICU neonates of the whole province,and the isolation rates of drug-resistant strains are high.It is grossly necessary for the reasonable clinical use of antibiotics to carry out the bacterial drug resistance surveillance.

Objective:To investigate the clinical value of AB classification combined with Arima classification for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCC).Methods:From July 2017 to December 2022, 76 cases of SESCC receiving endoscopic submucosal dissection and intra-epithelial papillary capillary loops (IPCL) AB classification as type B2 in Ningbo Medical Center Lihuili Hospital and Jiangsu Province Hospital of Chinese Medicine were included in the study. IPCL was reclassified according to Arima classification. The depth of infiltration determined by pathology was the gold standard. The sensitivity, the specificity, the positive predictive value and the negative predictive value of B2-Arima combined classification in predicting the invasion depth of SESCC were analyzed.Results:In the 76 cases of type B2 IPCL lesions, 31 cases (40.79%) were T1a-MM/T1b-SM1 SESCC. The sensitivity, the specificity, the positive predictive value, the negative predictive value and the diagnostic accuracy of type B2 IPCL to predict T1a-MM/T1b-SM1 SESCC were 70.45% (31/44), 79.64% (176/221), 40.79% (31/76), 93.12% (176/189), and 78.11% (207/265), respectively. After Arima classification, the above corresponding indicators of type B2-4ML and type B2-AVA-4M IPCL in predicting T1a-MM/T1b-SM1 SESCC were 61.36% (27/44), 88.24% (195/221), 50.94% (27/53), 91.98% (195/212), 83.77% (222/265) and 38.64% (17/44), 94.57% (209/221), 58.62% (17/29), 88.56% (209/236), 85.28% (226/265), respectively.Conclusion:B2 IPCL combined with Arima classification can improve the diagnostic accuracy of T1a-MM/T1b-SM1 ESSCC.

The gastric fundus fornix and upper part of the gastric body pose challenges for endoscopic submucosal dissection (ESD), resulting in unsatisfactory resection outcomes for lesions in these areas,because of the difficulty in the endoscope reaching the lesion site. Drawing inspiration from the formation of α loop during flexible colonoscopy and double-channel multibending gastroscope, a single-channel treatment gastroscope was utilized to create a multibending state (referred to as single-channel endoscope multibending method, SCMB). This method was employed to treat 6 patients with lesions in the stomach at Digestive Endoscopy Center of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2021 to December 2021. There were 3 cases in the gastric fundus fornix, 2 cases in the greater curvature on the upper part of the gastric body, and 1 case in the posterior wall of gastric fundus and subcardia. After 2-3 attempts during surgery, SCMB was successfully performed in all cases within 60-120 seconds. All 6 cases completed successful endoscopic resection within 20-80 minutes without significant complications, including 4 cases of ESD and 2 cases of endoscopic full-thickness resection (EFR). Preliminary results indicate that SCMB method during ESD and its derivative technologies are both safe and effective for lesions in challenging areas where gastric ESD is difficult to perform. During surgery, this approach facilitates the front end of endoscope access to the lesion, providing a clear visual field and a stable dissection plane.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

Objective:To explore regulatory effects of short-chain fatty acids (SCFA) on hypoxia-induced oxidative stress and activation of pancreatic stellate cells (PSCs) .Methods:PSCs were cultured in normoxia or hypoxia conditions to establish normoxia or hypoxia group. PSCs were pre-treated with SCFA working solution (10 mmol/L sodium acetate, 0.5 mmol/L sodium propionate and 0.5 mmol/L sodium butyrate), and then cultured in hypoxia conditions to establish the hypoxia-SCFA group. PSCs pre-treated by normal saline was set as the hypoxia-control group. The relative growth viability of the cells was detected by the CCK-8 assay. Relative levels of reactive oxygen species (ROS) were detected by DCFH-DA fluorescence probe method. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. Protein expression of cyclin-associated marker cyclin A and cyclin D, hypoxic marker HIF1α, activation marker α-SMA, and antioxidant marker NRF2 and HO-1 was detected by western blotting.Results:The relative viability of PSCs in hypoxia group was significantly higher than that in normoxia group at 48 h (1.23±0.05 vs 0.99±0.04), but the relative viability of hypoxia-SCFA group was significantly lower than that of the hypoxic-control group at both 36 h and 48 h (0.69±0.01 vs 0.86±0.03, 0.86±0.02 vs 1.25±0.05). The relative level of ROS was significantly higher in hypoxia group than normoxia group (1.74±0.11 vs 1.00±0.10). The relative level of ROS was significantly lower in the hypoxia-SCFA group than the hypoxia-control group (1.39±0.14 vs 1.66±0.11). The fluorescence signals of JC-1 polymer in hypoxia group were significantly higher than those in normoxia group (1.36±0.05 vs 1.00±0.11), whereas the fluorescence signals of JC-1 polymer were significantly lower in hypoxia-SCFA group than in hypoxia-control group (1.11±0.03 vs 1.32±0.06). The expression of cyclin A, cyclin D, HIF1α, α-SMA, NRF2, and HO-1 was significantly higher in hypoxia group than those in normoxia group (1.19±0.01 vs 0.63±0.02, 0.93±0.02 vs 0.83±0.03, 1.18±0.07 vs 0.41±0.02, 1.19±0.14 vs 0.66±0.04, 1.22±0.11 vs 0.61±0.04, 1.28±0.12 vs 0.68±0.02), but the expression of cyclin A, cyclin D, α-SMA, NRF2, and HO-1 in Hypoxia-SCFA group was significantly lower than those in hypoxia-control group (0.79±0.04 vs 1.15±0.03, 0.88±0.01 vs 0.95±0.03, 0.87±0.01 vs 1.18±0.05, 0.84±0.01 vs 1.22±0.04, and 0.92±0.02 vs 1.27±0.06). All these differences were statistically significant (all P values <0.05) . Conclusions:SCFA significantly improves the oxidative stress state of PSCs under hypoxic conditions, maintains the stability of mitochondrial membrane potential, and inhibites hypoxia-induced activation of PSCs.

Objective To investigate the correlation between the level of circulating placental growth factor(PLGF)and the severity of preeclampsia(PE),maternal and infant outcomes and placental pathology.Methods A total of 159 PE patients were selected as the study subjects and divided into the PE1 group(62 PE patients with termination of pregnancy<34 weeks)and the PE2 group(97 PE patients with termination of pregnancy≥34 weeks)according to the gestational age of pregnancy termination.A total of 107 non-PE patients who gave birth during the same period were selected as the control group.Patients were divided into two groups according to the gestational age of termination:the non-PE1 group(41 non-PE patients with termination of pregnancy at<34 weeks)and the non-PE2 group(66 non-PE patients with termination of pregnancy at≥34 weeks).General data were collected in each group of pregnant women,including age,body mass index(BMI),admission systolic blood pressure,diastolic blood pressure,24 h urinary protein quantity,gestational times,presence of FGR and fetal embarrassment.General information of newborns during the operation were collected,for example,whether there was fecal contamination of amniotic fluid,neonatal asphyxia,and days of newborn stayed in NICU.PLGF in venous blood of pregnant women was detected on the day of delivery.The placenta was pathologically detected and scored.After delivery,blood gas of umbilical artery was analyzed,and PH(pH),base surplus(BE),lactic acid(LAC)were recorded.Results There were no significant differences in age,gestational times and delivery times between the PE1 group and the PE2 group and the corresponding the non-PE1 group and the non-PE2 group.BMI was higher in the PE1 group and the PE2 group than that in the non-PE1 group and the non-PE2 group.PLGF was lower in the PE1 group and the PE2 group than that in the non-PE1 group and the non-PE2 group,respectively,and PLGF was lower in the PE1 group than that in the PE2 group(P＜0.05).The 24 h urinary protein quantity,systolic blood pressure,diastolic blood pressure and pathological changes of placenta were higher in the PE1 group than those in the PE2 group(P＜0.05).There were no significant differences in fecal staining of amniotic fluid,fetal embarrassed condition and pH value of umbilical artery blood gas during delivery between the PE1 group and the PE2 group.Compared with the PE2 group,the proportion of neonatal asphyxia and FGR,the umbilical artery blood gas LAC were increased,the BE value was decreased,and the time of staying in NICU was prolonged in the PE1 group(P＜0.05).Conclusion The level of circulating PLGF is decreased in patients with preeclampsia.PLGF has certain value in evaluating PE and predicting adverse pregnancy outcome.