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 explore the regulatory effect of Lingzhu Granules on the PI3K/Akt signaling pathway in the rats with polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods Fe-male Sprague-Dawley(SD)rats aged 3 weeks d old were selected to establish the model by using the DHEA method.The intervention treatment was administered by different doses of Lingzhu Granules and the homeostasis model as-sessment of insulin resistance(HOMA-IR)was calculated.The relative expression levels of PI3K,Akt,GSK-3β and GLUT4 mRNA in the ovaries was detected by RT-PCR.The expression levels of PI3K and Akt were detected by Western blot.Results Compared with the model control group,the rat body weight in the medium and high doses Lingzhu Granules groups was significantly reduced(P＜0.05).The fasting blood glucose,fasting insulin and HOMA-IR index in the Lingzhu Granules low,medium and high doses groups were significantly lower than those in the model control group,and the differences were statistically significant(P＜0.01).The mRNA relative expression levels of PI3K,Akt,GSK-3β and GLUT4 in the Lingzhu Granules medium and high doses groups all were higher than those in the model control group(P＜0.05).The relative expression levels of PI3K and Akt in the ovarian tissue in the Lingzhu Granules low,medium and high doses groups were higher than those in the model control group,and the differences were statistically significant(P＜0.05).Conclusion Lingzhu Granules could effectively improve the insulin resistance status of PCOS rats by enhancing the synthesis of PI3K and Akt.

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 explore the therapeutic effect and mechanism of pachymic acid(PA)on Helicobacter py-lori(Hp)-associated gastritis in rats.Methods A rat model of Hp-associated gastritis was established;all rats were separated into control group(CT group),model group(group M),PA low-dose group(PA L group),PA high-dose group(PA H group),and PA H+phosphatidylinositol 3-kinase(PI3K)activator(740 Y-P)group;the gastric mucosal injury index(UI)of rats in each group was evaluated,transmission electron microscopy was applied to observe the morphology of gastric mucosal cells.HE staining was applied to evaluate the pathological characteristics of gastric mucosa.ELISA was applied to detect the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-10,induc-ible nitric oxide synthase(iNOS),and superoxide dismutase(SOD)in gastric tissue.Western blot method was applied to detect the expression of PI3K,phosphorylated PI3K(p-PI3K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,and p-NF-κB p65 proteins.Results Compared with the CT group,the gastric mucosa erosion,epithelial ede-ma,congestion,and severe ulcers were observed in the group M,with epithelial cell pyknosis and inflammatory cell in-filtration,the UI,IL-6,TNF-α,iNOS,and the expression levels of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins increased,the levels of IL-10 and SOD decreased(P<0.05);compared with group M,the gastric mucosal damage and inflammatory cell infiltration in the PA L and PA H groups were improved,the UI,IL-6,TNF-α,iNOS by the host animal and the expression of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins all decreased,the level of IL-10 and SOD was increased(P<0.05);compared with the PA H group,the pathological damage of the gastric mucosa in the PA H+740 Y-P group was aggravated,with epithelial cell pyknosis.The UI,IL-6,TNF-α,iNOS,and the expression of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins increased,the levels of IL-10 and SOD decreased(P<0.05).Conclusions PA might facilitate the treatment of Hp-associated gastritis in rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.

ObjectiveTo investigate the efficacy and safety of Shengxiantang in the treatment of early Parkinson's disease with autonomic dysfunction of Qi deficiency pattern. MethodA total of 82 eligible patients were randomized into control group （41 cases） and traditional Chinese medicine （TCM） group （41 cases）. On the basis of standardized treatment of western medicine， TCM group was prescribed Shengxiantang while control group were treated with placebo for 12 consecutive weeks additionally. Scale for Outcomes in Parkinson's Disease-Autonomic （SCOPA-AUT） questionnaire， Unified Parkinson's Disease Rating Scale （UPDRS）， Traditional Chinese Medicine Qi Deficiency Symptom Score of Parkinson's Disease （TCMQDSSPD）， serum levels of glutathione peroxidase （GPx） and superoxide dismutase （SOD）， daily dosage of pramipexole and levodopa and benserazide hydrochloride， and safety index were evaluated both before and after treatment. ResultAfter treatment， the total score of SCOPA-AUT， gastrointestinal score， urinary score， and thermoregulatory score in the control group were higher than those before treatment （P<0.01）， while the above sores in the TCM group were lower than those before treatment （P<0.05， P<0.01）. In addition， the cardiovascular score， pupillomotor score， and sexual score in two groups showed no significant difference from those before treatment. After treatment， the total score of SCOPA-AUT， gastrointestinal score， urinary score， and thermoregulatory score in the TCM group were lower than those in the control group （P<0.05， P<0.01）， and cardiovascular score， pupillomotor score， and sexual score showed no significant difference between two groups. After treatment， the total score of TCMQDSSPD， main symptom scores， and minor symptom scores in the control group had no significant difference from those before treatment. The total score of TCMQDSSPD and minor symptom scores of TCM group were lower than those before treatment （P<0.01）， while the main symptom scores of the TCM group showed no significant difference from those before treatment. After treatment， the UPDRS score， serum GPx and SOD levels， and daily dosage of pramipexole and levodopa and benserazide hydrochloride demonstrated no significant difference from those before treatment in the two groups and between the two groups. No abnormality was found in the safety indexes. ConclusionBased on the standardized treatment of western medicine， Shengxiantang can effectively and safely improve the autonomic symptoms of gastrointestinal system， urinary system， and thermoregulation， as well as the symptoms of Qi deficiency syndrome in early Parkinson's disease with autonomic dysfunction.

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.

Objective To evaluate the measurement uncertainty of the detecting procedure of amino acids and carnitines by the Waters ACQUITY TQD tandem mass spectrometer and PerkinElmer NeoBaseTM non‐derivatized MSMS kit ,and to discuss the meaning of evaluation .Methods According to the method provided by the Medical Laboratories‐Evaluation and Expression of Measurement Uncertainty ,the internal quality control was detected by using two different batch codes of kit for 20 d ,once before and after the routine sample detection on each working day ,the detector were randomly changed ,and then the measurement uncer‐tainty introduced by measurement reproducibility was calculated;the amino acid external assessment quality control data in 20 times of neonatal hereditary metabolic disease tandem mass spectrometry screening provided by the National Center for Clinical Laborato‐ry in 2014 and 2015 ,and the same and 16 times of carnitines external assessment quality control data were performed the statistics , and then the measurement uncertainty introduced by bias was calculated .Next the relative standard uncertainty and the relative ex‐panded uncertainty according to the measurement uncertainty introduced by bias and measurement reproducibility were calculated . The allowed total error indicators of amino acid and carnitines external quality assessment in the neonatal hereditary metabolic dis‐ease tandem mass spectrometry screening by the National Center for Clinical Laboratory were used as the target expanded uncer‐tainty .Results The relative expanded uncertainties of citrulline ,methionine ,phenylalanine ,propionyl carnitine ,octanoyl carnitine , dodecanoyl carnitine ,palmitoyl carnitine and octadecanoyl carnitine were 19 .1% -26 .1% (k=2) ,which were smaller than the tar‐get uncertainty .The relative expanded uncertainties of leucine ,tyrosine ,valine ,free carnitine were 31 .0% -43 .3% (k=2) ,which were greater than the target uncertainty .The uncertainty of isovaleryl carnitine needed to be estimated separately .Conclusion As‐sessing the measurement uncertainty of the detecting procedure of amino acids and carnitines by the non‐derivatized tandem mass spectrometer method can not only provide an opportunity for continuously improving the detection quality ,but also can help the ex‐perimental technique staffs to interpret the test data correctly and the clinician to use the detection reports correctly .

ObjectiveTo explore changes of serum adiponectin and insulin resistance in patients with endometrial cancer and to evaluate the clinical significance and correlation.MethodsThe serum levels ofadiponectinandfastinginsulinweredeterminedbyELISA, electro-chemilluminometryand radioimmunoassay in 35 patients with endometrial cancer [ all patients divided into two groups,A1 group belonged to without postmenopausal when first visiting (n =20),A2 group belonged to postmenopausal when first visiting (n ＝ 15 ) ] and 30 cases of health control.The result of homeostasis nodel assessment-insulin resistance (HOMA-IR) index was calculated.ResultsThe levels of adiponectin in A1 group was lower than that ofhealth control group [(6.7±1.1) versus (10.0 ±1.4) ng/L,P＜0.05],and HOMA-IR was higher than that of health control group ( 3.5 ± 1.8 versus 1.1 ± 0.7,P ＜ 0.05 ).While there were not significant difference between A2 group and health control group (P ＞ 0.05 ).Adiponectin and insulin resistance was negatively correlated ( r =- 0.389,P ＜ 0.05 ).Conclusion Adiponectin reducing and insulin resistance in reproductive age patients may be the independent factors to promote endometrial cancers.

Objective To evaluate the clinical effect of ambulatory labor analgesia used in latent phase of the first stage of labor, which include labor progress, Apgar score after ambulatory labor analgesia begun to use when the cervix was different size dilatated. Methods Seventy-five parturient primiparas who had no complication were randomly divided into three groups: group Ⅰ: ambulatory labor analgesia was begun to use when the cervix was 1.0 cm dilated, group Ⅱ: ambulatory labor analgesia was begun to use when the cervix was 2-3 cm dilated, group Ⅲ: control group without use of ambulatory labor analgesia. Analgesic effects were observed, changes of uterine contraction were recorded by fetal monitor. Meanwhile, total stage of labor ,outcome of delivery and Apgar score were recorded. Results Duration of total stage of labor had no significant difference between group Ⅰ and group Ⅲ.The duration of the first labor stage was significantly longer in group Ⅰ than that in group Ⅱ(P