This study focuses on the microenvironment acidification caused by metabolic abnormalities and ion balance disturbances during cardiac ischemia, which can significantly trigger drug resistance and thus limit the therapeutic effect of coronary heart disease. To address this issue, we delve into the potential role of carbonic anhydrase inhibitors in enhancing drug efficacy through pH regulation. First, we evaluated the potential of the carbonic anhydrase inhibitor acetazolamide, in combination with aspirin, in alleviating myocardial hypoxic injury in a cellular model. Through high-throughput screening techniques, we systematically analyzed the synergistic effect of this drug combination and determined the optimal ratio. Next, we modified the structure of aspirin using acetazolamide as the structural basis, aiming to create novel derivatives with stronger myocardial protective activity. Using in vitro and in vivo models of myocardial hypoxic injury, we evaluated the biological activity and therapeutic efficacy of these derived compounds in detail. Animal experiments were approved by the Animal Ethics Committee of Southeast University (Ethics No. 20240109001). The results showed that the structurally modified aspirin derivatives exhibited significant synergistic effects in alleviating myocardial hypoxic injury. This study reveals the mechanism of action of carbonic anhydrase inhibitors in the treatment of coronary heart disease and provides experimental and theoretical evidence for the development of novel coronary heart disease treatment drugs, which has important guiding significance for drug design and coronary heart disease treatment strategies.

Aim To express and purify rhα-Gal A with a 6 X His tag via using a serum-free expression system in high-density suspension culture of Chinese hamster ovary cells ( CHO-S) , and to verify the scavenging effect of rhα-Gal A on globular trisaccharide ceramide (Gb3 or GL3) . Methods The construction of recombinant protein expression vector, pcDNA4-GLA, was achieved by fusing the human α-galactosidase cDNA, gla, with 6 X His tag and artificial DNA synthesis. The expression plasmid was transfected into the suspended CHO-S to express rhα-Gal A and then purified. Following this procedure, we determined rhα-Gal A's expression, the enzymatic activity, and the glycosylation of the recombinant enzyme. Co-incubation with cultured cells was performed to examine whether rhα-Gal A could be taken up into the cells and effectively remove Gb3 substrates. Results rhα-Gal A was successfully expressed and purified after transiently transfecting pcDNA4-GLA into the suspended CHO-S, and the yield was up to (100 ±20. 6) mg • L

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m², fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m², male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.
Adult ; Aged ; Humans ; Male ; Female ; Middle Aged ; Aged, 80 and over ; Blood Pressure/physiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Antihypertensive Agents/therapeutic use* ; Smoking ; Body Mass Index ; Hypertension/epidemiology*

Humans ; Adult ; Mucormycosis ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Antifungal Agents

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed. METHODS: Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System. RESULTS: After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P<0.05), and the pericardium meridian microcirculation perfusion (PMP) showed no significant differences at 3 stages (P>0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P<0.05), and PMP decreased obviously after acupuncture (P<0.05). The PMP in the LU 7 and LI 10 groups were slightly elevated (both P>0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05). CONCLUSIONS Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Electroacupuncture ; Meridians ; Microcirculation ; Myocardial Ischemia ; Perfusion ; Pericardium ; Rats ; Rats, Sprague-Dawley

Objective: To understand the risk factors and antibiotics-resistant patterns of invasive Acinetobacter baumannii infection in Children. Methods: This retrospective study was conducted in 6 tertiary hospitals from January 2016 to December 2018. The basic information, clinical data and the results of antimicrobial susceptibility testing were collected from the 98 pediatric inpatients with Acinetobacter baumannii isolated from blood or cerebrospinal fluid and analyzed. According to the susceptibility of the infected strains to carbapenems, they were divided into carbapenem-sensitive Acinetobacter baumannii (CSAB) group and carbapenem-resistant Acinetobacter baumannii (CRAB) group. According to the possible sources of infection, they were divided into nosocomial infection group and community infection group. Chi-square test or Fisher exact test were used to analyze categorical variables and rank sum test were used to analyze continuous variables. The risk factors of invasive CRAB infection in children were analyzed by Logistic regression. Result: There were 56 males and 42 females in 98 cases. The onset age of patients was 8 (2, 24) months. There were 62 cases (63%) from rural area. A total of 87 cases (89%) were confirmed with bloodstream infection, and 12 cases (12%) confirmed with meningitis (1 case was accompanied with bloodstream infection). In these patients, 66 cases (67%) received invasive medical procedures or surgery, 54 cases (55%) received carbapenems-containing therapy. Twenty-four cases were infected with CRAB, and 74 cases with CSAB. The onset age of cases in CRAB group was lower than that in CSAB group (4 (1, 9) vs. 10 (4, 24) months, Z=-2.16, P=0.031). The proportions of hospitalization in intensive care unit, carbapenem antibiotics using, pneumonia and adverse prognosis in CRAB group were higher than those in CSAB group (6 cases (25%) vs. 4 cases (5%), 18 cases (75%) vs. 36 cases (49%), 17 cases (71%) vs. 17 cases (23%), 6 cases (25%) vs. 4 cases (5%), χ²=5.61, 5.09, 18.32, 5.61, all P<0.05). Seventy-seven cases were nosocomial infection and 21 cases were hospital-acquired infection. The proportion of children hospitalized in high-risk wards for nosocomial infections, length of hospitalization, number of antimicrobial therapy received and duration of antimicrobial therapy were higher in the hospital associated infection group than those in the community acquired infection group (all P<0.05). Logistic regression analysis showed that children from rural area (OR=8.42, 95%CI 1.45-48.88), prior mechanical ventilation (OR=12.62, 95%CI 1.31-121.76), and prior antibiotic therapy (OR=4.90, 95%CI 1.35-17.72) were independent risk factors for CRAB infection. The resistance percentage of CSAB isolates to many classes of antibiotics was <6% except to gentamicin, which was as high as 20% (13/65). All CRAB isolates of resistant to ampicillin-sulbactam (20/20), cefepime (23/23), piperacillin (17/17), meropenem (23/23) and imipenem (24/24) were 100%. The resistance percentage to other antibiotics were up to 42%-96%. Conclusions: Most of invasive Acinetobacter baumannii infection in children in China are hospital-acquired. The outcome of invasive CRAB infection was poorer than that of CSAB infection. The drug resistance rate of CRAB strains isolated is high. Living in rural area, prior invasive mechanical ventilation and prior antibiotic therapy were independent risk factors for invasive CRAB infection. The prevention and control of nosocomial infection and appropriate use of antibiotics to reduce Acinetobacter baumannii infection.
Acinetobacter Infections/epidemiology* ; Acinetobacter baumannii ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/therapeutic use* ; Child ; Cross Infection/epidemiology* ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Retrospective Studies ; Risk Factors ; Sepsis