ObjectiveThis study aims to enhance of the farnesyl pyrophosphate（FPP） pool in Saccharomyces cerevisiae by heterologously expressing different farnesyl diphosphate synthases（FPSs） from various plants， thereby increasing the production of terpenoid compounds by the engineered yeast. MethodsRNA from mixed samples of roots， stems， and leaves of seven plants including Arabidopsis thaliana， Rosa rugosa， Artemisia annua， Centella asiatica， Humulus lupulus， Medicago sativa， and Panax ginseng was extracted by column chromatography and reverse transcribed into the first strand of complementary DNA（cDNA）， and based on the transcriptome data of the seven species of plants， sequence-specific primers were designed for CaFPS， RrFPS， MsFPS， HiFPS， PgFPS， AtFPS， and AaFPS， the full-length of the genes was cloned， and the genes were analyzed for bioinformatics in order to construct a pESC yeast shuttle vector. These seven plant-derived FPSs were further heterologously expressed in the previous constructed β-elemene-producing yeast， and the yield of β-elemene was indicated for their catalytic acivities. ResultsThe coding sequences of CaFPS， RrFPS， MsFPS， HiFPS， PgFPS， AtFPS， and AaFPS were all of 1 021 bp in length and encoding 301 amino acids， all of which were similarly related to the endogenous FPS-encoding gene（ERG20） in S. cerevisiae. After heterologous expression， RrFPS was identified as the most effective in catalyzing the synthesis of FPP from isopentenyl pyrophosphate（IPP） and dimethylallyl pyrophosphate（DMAPP）. Compared to the control strains， the RrFPS overexpressed yeast strains YB-1-Rr and YB-3-Rr increased the production of β-elemene by 231.25% and 189.3%， respectively. ConclusionBy comparing the functions of FPS-encoding genes from seven different plant sources， it is determined that the protein encoded by the RrFPS from R. rugosa has the best catalytic ability， which can provide key genetic elements for the construction of engineered yeast strain constructs with high terpenoid production.

Objective To explore the influencing factors of over active bladder(OAB)in patients with cerebral small vessel disease(CSVD)and its correlation with CSVD imaging markers.Meth-ods A total of 163 elderly CSVD patients admitted in our hospital from January 2021 to Decem-ber 2022 were enrolled and divided into OAB group(37 cases)and non-OAB group(126 cases)based on the results of OAB rating scale.Mini-mental State Examination(MMSE)score,Fazekas scale score,and total CSVD burden score were recorded and compared between the two groups.Results The OAB group had older age,higher urinary frequency,larger proportions of nocturia,urgency,and urge incontinence ratio,increased Fazekas score,periventricular white matter hyper-intensity(PWMH)score and deep white matter hyperintensity(DWMH)score,and elevated total CSVD burden score and lower MMSE score than the non-OAB group(P＜0.05,P＜0.01).PWMH score and DWMH score were risk factors for the occurrence of OAB(P＜0.01).The OAB score was positively correlated with Fazekas score,PWMH score,and DWMH score in the CSVD patients(r=0.533,P=0.001;r=0.462,P=0.004;r=0.398,P=0.015).The occurrence of urgency urinary incontinence was positively correlated with Fazekas score and PWMH score in the CSVD patients(r=0.352,P=0.033;r=0.346,P=0.036).Conclusion PWMH and DWMH are risk factors for OAB occurrence in CSVD patients.

Objective To construct a quality control information system for the entire process of neonatal breastfeeding and evaluate its application effect.Methods Based on the"evidence-based guidelines for breastfeeding of inpatient newborns"and combined with clinical practice,hazard analysis and critical control point methods were applied to construct a quality control information system for the entire breastfeeding process,which includes medical order reminder module,knowledge assessment module,breast milk outside the hospital management module,breast milk inventory reminder module,and adverse feeding record module.The pure breastfeeding rate,qualified rate of breast milk quality,and incidence of adverse events of hospitalized newborns before the application of the system(June and August 2021)and after the application of the system(June and August 2022)were compared.Results After the implementation of the system,the pure breastfeeding rate of hospitalized newboms increased from 15.12％to 28.05％,with a statistically significant difference(x2=4.170,P=0.041).The qualified rate of breast milk quality increased from 68.44％to 96.79％,with a statistically significant difference(x2=531.853,P＜0.001).The incidence of adverse events decreased from 5.81％to 0,with a statistically significant difference(P=0.026).Conclusion The quality control information system for the entire process of breastfeeding accurately identified risks and warning signs against them,standardized the management of breast milk outside the hospital,improved the qualification rate of breast milk quality and pure breastfeeding rate,reduced adverse events of breastfeeding,and ensured the effectiveness and safety of breastfeeding.

Objective Improving the limb management strategy for patients undergoing coronary intervention through radial artery puncture and observe the application effect,and to provide scientific basis for the prevention of limb complications.Methods From March 2023 to February 2024,patients who underwent coronary intervention in the Cardiovascular Department of a Tertiary A hospital in Wenzhou City were selected.They were randomly di-vided into an experimental group of 241 cases and a control group of 236 cases using a random number table method.After surgery,they were all treated with a rotary hemostatic device for compression hemostasis.The experi-mental group implement improvement strategies for surgical limb management,specifically underwent a reverse Bar-beau test upon returning to the ward after surgery to achieve non-occlusive compression,followed by decompression every hour.The compression intensity of the control group was guided by palpating the distal radial artery pulsa-tion,and the first decompression was performed 1 hour after surgery,followed by decompression at intervals of every 2 hours.The main evaluation indicators are the incidence of surgical limb complications and simplified Chinese version of General Comfort Questionnaire(GCQ)scores in 2 groups of patients,while the secondary evaluation indi-cators are the duration of compression and the number of decompression times in both groups.Results The inci-dence of postoperative complications in the experimental group was 14.11%,which was statistically significant com-pared to 44.49%in the control group(χ2=53.308,P<0.001).The GCQ score of the experimental group was(77.71±5.43)points,which was higher than(74.66±5.83)points in the control group,and the difference was statistically signif-icant(t=-3.354,P=0.001).The compression duration of(172±52)minutes and decompression frequency of 2(2,3)in the experimental group were lower than(289±60)minutes and 4(3,4)in the control group,and the differences were statistically significant(P<0.001).Conclusion The non-occlusive compression method of the radial artery based on the reverse Barbeau test can significantly reduce limb complications in patients undergoing coronary inter-vention,shorten the duration of hemostatic compression,reduce the number of depressions,and improve patient com-fort.It provides objective basis for nursing staff to evaluate the intensity of hemostatic compression and the timing of decompression.

Objective:To explore the efficacy and safety of low-and medium-intensity resistance exercise in patients with chronic heart failure(CHF)combined with sarcopenia.Methods:In the randomized controlled study, 100 elderly patients with CHF combined with sarcopenia who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Baotou Medical College from October 2020 to August 2022 were selected and divided into the control group and the intervention group according to the randomized numerical scale method.In the control group, angiotensin-converting enzyme inhibitors/angiotensin receptor inhibitors, β receptor antagonists, diuretics and other standard heart failure medications were routinely given, as well as nutritional support, health education and guidance; in the intervention group, low-intensity resistance exercise was given in addition to the treatment of the control group, and the two groups were evaluated for the NYHA cardiac function classification, grip strength, 5 times sitting time, 6-meter walking time, serum B-type natriuretic peptide level before and after 12 weeks of treatment; limb skeletal muscle mass index(ASMI), visceral fat area, extracellular water ratio were measured by body composition analyzer; right ventricular internal diameter, left atrial internal diameter, left ventricular end-diastolic internal diameter, left ventricular ejection fraction(LVEF) were measured by echocardiography.Changes in each index before and after treatment were compared between the 2 groups.Serious adverse cardiovascular events related to training were followed up by outpatient clinic visits or telephone at 4-week interval over 12 weeks.Results:30 cases were dislodged because they could not adhere to the exercise or could not follow up on time, and finally 70 patients were included, 27 in the control group and 43 in the intervention group.Compared with pre-treatment, grip strength[(17.73±4.54)kg vs.(17.00±4.32)kg, t=8.969], limb skeletal muscle mass[(17.57±3.41)kg vs.(17.24±3.34)kg, t=7.170], and ASMI[(6.02±0.72)kg/m 2vs.(5.85±0.67)kg/m 2, t=6.866]were elevated in the intervention group after 12 weeks(all P<0.05); 5 times sitting up time[(16.17±3.25)s vs.(14.54±3.21)s, t=12.808, ]and 6-meter walking time[(12.30±3.24)s vs.(10.76±3.14)s, t=9.391]shortened(all P<0.05).Compared with pre-treatment, the intervention group showed reduced left ventricular end-diastolic internal diameter[(59.62±9.07)mm vs.(58.48±9.71)mm, t=4.552], increased LVEF[(34.69±7.93)% vs.(35.88±7.92)%, t=4.752], and increased extracellular water ratio[(39.27±7.74)% vs.(38.92±7.41)%, t=6.058]after 12 weeks(all P<0.05).At 12 weeks of follow-up, no training-related serious adverse events occurred in the intervention group.The difference in the incidence of serious adverse cardiovascular events between the two groups(3.70% vs.2.33%, P>0.05)was not statistically significant. Conclusions:Treatment combined with low-and moderate-intensity resistance exercise improves muscle mass, muscle strength, physical function, and cardiac function in elderly patients with CHF combined with sarcopenia without increasing the incidence of adverse events.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To analyze the electrophysiological characteristics and influencing factors of peripheral neuropathy in Parkinson's disease(PD)patients.Methods:Totally 68 PD patients and 30 controls were selected for neuroelectrophysiological evaluation, including items such as limb motor nerve terminal latency(LP)and amplitude and sensory nerve conduction velocity(SCV)and amplitude.Age, sex, serum folate, vitamin B 12, homocysteine and hemoglobin levels were also recorded for the two groups.The Hoehn-Yahr scale was used to assess patients and levodopa daily doses and levodopa equivalent daily doses were calculated.According to the criteria for neuroelectrophysiological abnormalities, 31 PD patients were found to have peripheral neuropathy and 37 PD patients did not have peripheral neuropathy. Results:In PD patients, a total of 952 peripheral nerves were examined, with 21.7% having motor nerve involvement(118/544)and 72.8%(297/of 408)having sensory nerve involvement.In the control group, a total of 420 peripheral nerves were examined, with 4.2%(10/240)having motor nerve involvement and 26.1%(47/180)having sensory nerve involvement.Compared with the control group, the wave amplitudes of motor nerve terminals were reduced in the PD group for the ulnar nerve( t=2.172/2.345, right/left), median nerve( t=2.104/2.543, right/left), and tibial nerve( t=2.340/2.444, right/left)(all P<0.05); compared with the control group, the wave amplitudes of sensory nerve terminals of the ulnar nerve( Z=3.535/3.439, right/ left), median nerve( Z=3.076/2.937, right/left), and peroneal nerve( Z=2.795/2.795, right/left)were all reduced in the PD group(all P<0.05); compared with the control group, sensory conduction velocities of the ulnar nerve( t=2.326/2.487, right/left), median nerve( t=3.269/2.386, right/left), and peroneal nerve( t=2.551/2.418, right/left)were prolonged(all P<0.05). The rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=149.814, P<0.001)was higher than that of abnormalities with motor nerve terminal wave amplitude in PD patients; the rate of abnormalities with the sensory nerve terminal wave amplitude( χ2=58.364, P<0.001)was higher than that of abnormalities with sensory conduction velocities.Logistic regression analysis showed that increased folic acid( OR=0.825, 95% CI: 0.637-0.990)and vitamin B 12( OR=0.996, 95% CI: 0.991-1.000)were protective factors for PD peripheral neuropathy; H-Y score, levodopa daily dose( OR=1.009, 95% CI: 1.003-1.015), and increased homocysteine( OR=1.151, 95% CI: 1.041-1.273)were risk factors for PD peripheral neuropathy.After excluding confounding factors, H-Y classification( OR=3.213, 95% CI: 1.342-7.713)remained an independent risk factor for peripheral nerve injury in PD patients. Conclusions:In PD patients with peripheral neuropathy, both motor nerves and sensory nerves are involved, sensory nerves are more significantly involved, and axonal damage is more important than myelin loss; increased H-Y classification is an independent risk factor for peripheral nerve injury in PD patients.

To analyze the influencing factors and clinical significance of fatigue in patients with Parkinson’s disease（PD）. Methods 155 patients with PD were selected from the Department of Neurology of the Second Affiliated Hospital of Baotou Medical College from January 2019 to December 2020.According to the fatigue severity scale（FSS），59 patients in the PD non fatigue group（FSS>4 points） and 96 patients in the PD fatigue group（FSS≤4 points）. Unified Parkinson’s disease rating scale Part III（MDS-UPDRS Ⅲ）、Hoehn-Yahr（H-Y）、Hamilton Depression Scale（HAMA）17，Hamilton Anxiety Scale（HAMD）14,Parkinson’s disease Sleep Scale（PDSS） Chinese version，simple mental state scale and so on. The physical fatigue and mental fatigue of PD patients were scored by fatigue Scale-14（fs-14）. The total scores of tremor items and postural abnormalities gait disorders were calculated according to the items of MDS UPDRS Ⅱ～Ⅲ. Results Compared with the non fatigue group，the mds-updrs Ⅲ，H-Y score，HAMA，HAMD and course of disease in the fatigue group were increased，and the PDSS was decreased（P<0.05）. Mds-updrs Ⅲ score（OR=1.105，P=0.011） and depression（OR=1.160，P=0.028） were independent risk factors for fatigue. Mental fatigue was positively and strongly correlated with HAMD（rs=0.792）；physical fatigue was positively and strongly correlated with mds-updrs Ⅲ（rs=0.645），total score of postural abnormalities gait disorders（rs=0.659），HAMA（rs=0.654） and H-Y score（rs=0.674），which was positively and strongly correlated with PDSS（rs=-0.674） negative strong correlation. Conclusion The incidence rate of fatigue in PD patients is high，and is associated with motor symptoms，sleep disorders，anxiety and depression.

Objective:To assess the nosocomial infection risk events of neonatology experienced by a hospital, for identifying those events deserving high priority in infection prevention and control and critical rooms of improvement, hence minimizing such risks of the hospital.Methods:The hazard vulnerability analysis was called into play, along with literature review and clinical practices, while the hazard vulnerability analysis team of neonatology of the hospital preliminarily screened the indexes in brainstorming method. Then the individual indexes from such screening evaluated by means of questionnaires, and the risk evaluation index system for neonatal infection prevention and control was formed in combination with the risk value evaluation table of Kaiser model. On such basis, an evaluation questionnaire for the prevention and control was developed.In May 2020, the team members scored the possibility and severity of these risk indexes in the form of questionnaire, calculated the hazard risk value, and divided the risk zones by matrix analysis.Results:The risk assessment index system of neonatology was composed of 11 management indexes, 20 implementation indexes and 7 outcome indexes. The top 5 indexes of hazard risk value were: incorrect hand hygiene method(39.20%), inadequate cleaning and disinfection of environmental object surface(39.04%), the formula was not used immediately when ready(38.19%), nosocomial infection outbreak(38.02%), and low hand hygiene compliance(37.99%). The indexes with high severity and low readiness include three indexes related to formula feeding and three indexes related to cleaning and disinfection of object surface. The matrix analysis results showed that there were 9 indexes in the high-risk zone, 7 indexes in the medium risk zone and 22 in the low-risk zone.Conclusions:This study identified risk management events in hospital infection management in neonatology by means of hazard vulnerability analysis. The neonatology administrators are recommended to prioritize indexes in the high risk zone, make a root cause analysis of those indexes of high risk value and low readiness and take intervention measures in time, hence reducing the incidence of nosocomial infection and avoiding the outbreak of nosocomial infection.

Studies have shown that plasma apolipoprotein B (ApoB) has a good predictive value for ischemic stroke and plays an important role in the prevention and treatment of ischemic stroke. More and more guidelines and consensus opinions began to recommend ApoB as a routine intervention target. This article reviews the biological characteristics, clinical detection advantages, and role and treatment prospect of ApoB in the prevention and treatment of ischemic stroke.