OBJECTIVE To explore the effects of esmolol on cardiac function， inflammatory factors and serum microRNA （miR）-29a and miR-129-5p in patients with acute anterior ST-segment elevation myocardial infarction after percutaneous coronary intervention （PCI）. METHODS A total of 120 patients with acute anterior ST-segment elevation myocardial infarction undergoing PCI in our hospital from April 2021 to June 2023 were selected and divided into control group （60 cases） and study group （60 cases） according to the random number table method. The control group was given conventional treatment， and the study group was additionally given Esmolol hydrochloride injection based on the control group for one week. The levels of cardiac function indexes （left ventricular ejection fraction， left ventricular end-systolic volume index， left ventricular end-diastolic diameter， peak ejection fraction， cardiac output）， inflammatory factors （C-reactive protein， myeloperoxidase， interleukin-6， brain natriuretic peptide， homocysteine） myocardial enzyme indexes （creatine kinase isoenzyme， β2-microglobulin， cardiac troponin Ⅰ）， and serum expression of miR-29a and miR-129-5p were observed in two groups， and the occurrence of ADR was recorded. RESULTS After one week of treatment， left ventricular ejection fraction， peak ejection fraction， cardiac output， and the expression of miR-129-5p in two groups was significantly higher than before treatment （P＜0.05）， while left ventricular end-systolic volume index， left ventricular end-diastolic diameter， inflammatory factors and myocardial enzyme index levels， and the expression of miR-29a were significantly lower than before treatment （P＜ 0.05）. The study group was significantly better than the control group （except for the creatine kinase-MB） （P＜0.05）. There was no statistically significant difference in the incidence of symptomatic hypotension， symptomatic bradycardia， cardiogenic shock， and arrhythmia between two groups （P＞0.05）. CONCLUSIONS Esmolol can improve cardiac function， reduce inflammatory factors， lessen myocardial injury， and regulate serum expressions of miR-29a and miR-129-5p in patients with acute anterior ST- segment elevation myocardial infarction after PCI， with good safety.

Objective To investigate the changes in interleukin-34 (IL-34)levels in serum and bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and their prognostic value. Methods A total of 66 patients with severe pneumonia (severe pneumonia group), 35 patients with non-severe pneumonia (non-severe pneumonia group), and 27 healthy adults (control group) were enrolled. The severe pneumonia group was further divided into survival group of 38 patients and non-survival group of 28 patients based on 28-day survival. Clinical data of all subjects were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive power of serum IL-34 and relative IL-34 gene expression in BALF for 28-day mortality in patients with severe pneumonia, as well as the predictive power of serum IL-34 for severe pneumonia. Kaplan-Meier survival curves were plotted, and the Log-rank test was used to compare cumulative survival rates. Cox regression analysis was conducted to explore risk factors for 28-day mortality in patients with severe pneumonia. Pearson correlation analysis was used to assess the correlation between serum IL-34 levels and relative IL-34 gene expression in BALF of patients with severe pneumonia. Results Serum IL-34 levels were higher in the severe pneumonia group than those in the non-severe pneumonia group, and were higher in the non-severe pneumonia group than in the control group (P < 0.05). Serum IL-34 levels and relative IL-34 gene expression in BALF were higher in the non-survival group than in the survival group (P < 0.05). ROC curve analysis showed that the areas under the curve for predicting 28-day mortality in patients with severe pneumonia were 0.908 for serum IL-34 levels and 0.878 for relative IL-34 gene expression in BALF. The optimal cutoff value for serum IL-34 levels in predicting severe pneumonia was 129.9 pg/mL. Multivariate Cox regression analysis showed that increased serum IL-34 levels and increased relative IL-34 gene expression in BALF were independent risk factors for 28-day mortality in patients with severe pneumonia (P < 0.05). The Kaplan-Meier survival analysis results indicate that, with a cutoff value of 129.9 pg/mL, patients with severe pneumonia who had high serum levels of IL-34 exhibited a lower cumulative survival rate compared to those with low IL-34 level(Log-rank P < 0.001). Conclusion Serum IL-34 levels are significantly increased in patients with severe pneumonia, and relative IL-34 gene expression in BALF is positively correlated with serum IL-34 levels. Both can be used as indicators for predicting the prognosis of 28-day mortality in patients with severe pneumonia.

Objective:To explore the clinical efficacy of the San Diego osteotomy in treating developmental dysplasia of the hip (DDH) in children.Methods:A retrospective analysis was conducted on 33 pediatric cases of posterolateral acetabular dysplasia treated with the San Diego osteotomy at the 920th Hospital of the People's Liberation Army Joint Logistics Support Force in China from August 2018 to August 2022. The cohort included 3 males (4 hips) and 30 females (36 hips), with an average age of 4.9±1.4 years (range, 2-8 years). Among these, 32 cases (38 hips) were diagnosed with DDH, and 1 case (2 hips) with paralytic dislocation of the hip. According to the T?nnis classification, 3 hips were classified as type II, 25 hips as type III, and 12 hips as type IV. The San Diego osteotomy technique was utilized to enhance the posterior lateral acetabular coverage, combined with femoral osteotomy to adjust the hip abduction, flexion, and adduction angles. Postoperative outcomes were assessed using the modified Severin radiographic classification and the McKay grading system.Results:All 33 patients were followed up for an average of 37.70±18.44 months (range, 12-74 months). No cases of postoperative hip redislocation or residual acetabular underdevelopment were observed. The hip abduction angle improved from 24.98°±3.48° at 6 weeks postoperatively to 37.28°±4.63° at the 3-month follow-up, and 64.05°±3.82° at the 6-month follow-up, with a statistically significant difference ( F=77.327, P<0.001). The hip flexion angle increased from 26.34°±5.05° at 6 weeks postoperatively to 76.53°±4.38° at 3 months, and 106.47°±2.29° at 6 months, also showing a statistically significant difference ( F=54.377, P<0.001). The hip adduction angle progressed from 1.73°±1.18° at 6 weeks postoperatively to 12.33°±1.97° at 3 months, and 29.03°±4.17° at 6 months, with a significant difference ( F=45.162, P<0.001). The McKay hip joint grading system indicated 11 excellent, 20 good, and 9 acceptable outcomes, yielding an overall excellent and good rate of 78%. The Severin radiographic grading revealed 16 hips at grade I and 24 hips at grade II. Five patients (5 hips) experienced transient vascular compromise of the femoral head at 3 months postoperatively, which resolved after a 1-month non-weight-bearing period. At the final follow-up, one patient had residual femoral head enlargement in the right hip, while the remaining 32 cases showed satisfactory ossification and remodeling of the femoral head. Conclusion:The San Diego osteotomy significantly enhances hip joint range of motion and results in satisfactory hip joint function in children with developmental dysplasia of the hip

Iron metabolism plays a regulatory role in various metabolic diseases, and excessive iron accumulation can increase the risk of metabolic diseases, especially type 2 diabetes mellitus (T2DM). Pathological processes such as iron deposition, iron overload, and ferroptosis can activate oxidative stress, lipid peroxidation, autophagy, and other processes, promote the amplification of inflammatory reactions and the reduction of antioxidant capacity, gradually decline the function of pancreatic islet β-cells, thereby promoting the occurrence and development of T2DM. Glucagon-like peptide-1 (GLP-1) is a physiological hormone secreted by intestinal L cells. GLP-1 analogs or GLP-1 receptor agonists can regulate the body's iron metabolism process, inhibit iron deposition, iron overload, and ferroptosis-related inflammatory reactions, promote the proliferation and differentiation of pancreatic islet β-cells, thereby reducing insulin resistance, inhibiting endothelial cell damage, and playing an important role in the prevention and treatmentof T2DM and its complications.

Objective:To investigate the short-term efficacy of rotational femoral neck osteotomy with preservation of the round ligament in the treatment of subchondral insufficiency fracture of the femoral head (SIFFH) in young and middle-aged people.Methods:A retrospective case series study was used to analyze the clinical data of 13 patients with SIFFH, who were admitted to 920th Hospital of Joint Logistics Support Force from January 2017 to January 2022. The patients included 10 males and 3 females, aged 22-49 years [(33.5±8.3)years]. There were 6 patients with fracture on the left hip and 7 on the right hip. All the patients were treated by rotational femoral neck osteotomy with preservation of the round ligament. Postoperatively, standardized joint functional training was given. The operative time and intraoperative bleeding were recorded. The modified Harris hip score and visual analogue score (VAS) were compared preoperatively, at 3, 6 months postoperatively and at the final follow-up. Radiological examinations were used to observe the occurrence of any collapse of the femoral head, non-union at osteotomy site or other complications.Results:The patients were followed up for 13-24 months [(17.9±3.1)months]. The operative time was (127.3±9.8)minutes, with the intraoperative bleeding of (393.9±21.9)ml. The values of modified Harris hip score were (61.6±3.3)points, (80.2±4.4)points, and (91.9±4.1)points at 3, 6 months postoperatively and at the final follow-up, respectively, being significantly higher than the preoperative (51.4±3.5)points (all P<0.05), and there were significant differences between different postoperative timepoints (all P<0.05). The values of VAS were (4.9±1.1)points, (3.0±0.9)points, and (1.4±0.5)points at 3, 6 months postoperatively and at the final follow-up, respectively, being significantly lower than preoperative (6.7±0.9)points (all P<0.05), and there were significant differences between different postoperative timepoints (all P<0.05). Imaging examination showed no femoral head collapse, with all the bones healed at the osteotomy site. There were no serious complications such as bone non-union, incision infection or peripheral nerve injury. Conclusion:Rotational femoral neck osteotomy with preservation of the round ligament in treating SIFFH in the young and middle-aged population has the advantages of shortened operative time, less intraoperative bleeding, promoted hip function recovery, attenuated pain and decreased complications, showing a satisfactory early effect.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective:To automatically synthesize Al 18F-fibroblast activation protein inhibitor (FAPI)-74, and explore its value of clinical application. Methods:Al 18F-FAPI-74 was synthesized automatically by the commercial synthesis module CFN-MPS-100, and its yield, radiochemical purity and stability were determined. Sixteen normal Kunming (KM) mice were randomly divided into 4 groups and euthanized at 10, 30, 60 and 90 min after Al 18F-FAPI-74 injection, and the biodistribution was measured. MicroPET/CT dynamic scanning (60 min) was performed in 5 rat pancreatic tumor-bearing BALB/c nude mice to observe the tumor uptake. Al 18F-FAPI-74 PET/CT imaging was performed on 3 volunteers (1 male, 2 females; age: 37, 41, 43 years) to evaluate the clinical application value of Al 18F-FAPI-74. Results:The automated synthesis time of Al 18F-FAPI-74 was about 35 min, with the synthesis yield of (21.34±3.86)% (without attenuation correction, n=5) and the radiochemical purity more than 99%. The radiochemical purity was still more than 96% after placement at 37 ℃ for 6 h. Biodistribution in normal mice and microPET/CT dynamic scanning in tumor-bearing nude mice showed that consistently high uptake in the kidneys and bladder, and the tumor uptake was the highest at 20 min, and the maximum tumor-to-muscle ratio was 3.16±0.01 at 60 min. PET/CT imaging on volunteers showed that there was a small amount of uptake in myocardium, most organs such as the liver and lung had background uptake, and the maximum SUV max of persistent high uptake of tumor was 17.08. Conclusions:Al 18F-FAPI-74 has the advantages of simple synthesis, high yield, stable quality and good imaging performance in mice and volunteers. It is a kind of imaging agent that meets the requirements of clinical diagnosis.

Objective:To explore the influencing factors of Internet + nursing service quality.Methods:Using a convenience sampling method, 290 nursing staff who had implemented Internet+ nursing services in Beijing and Tianjin were selected for a questionnaire survey from January to February 2022, and structural equation model was used to analyze the influencing factors and the path of action of service quality.Results:The structural equations constructed fit well, with gender, degree of service difficulty and degree of service motivation being direct influences on the quality of Internet+ nursing services, with degree of service difficulty also having an indirect effect on service quality through degree of service motivation.Conclusions:The quality of Internet+ nursing services is influenced by multiple factors and pathways. The relevant authorities can conduct a comprehensive assessment of the factors and pathways and manage them in a targeted manner to improve the quality of services.

Objective:To construct the "Internet+ Obstetrical Nursing Service" quality evaluation index system, so as to provide a basis for evaluation of quality of "Internet+ Obstetrical Nursing Service".Methods:The overall study period was from March 1 to July 10, 2021. Taking Donabedian three dimensional theory and service quality (SERVQUAL) evaluation model as the theoretical basis, through literature retrieval and referring to relevant policies of "Internet+ Nursing Service" in China, the quality evaluation index system of "Internet+ Obstetrical Nursing Service" was initially formulated. The Delphi method was used to conduct 3 rounds of correspondence to 16 experts and the weight of each indicator was determined based on analytic hierarchy process.Results:In the three rounds of letter inquiries, the effective recovery rates of the questionnaires were 100.0% (16/16) , 100.0% (16/16) and 93.8% (15/16) , respectively. The expert authority coefficients were 0.847, 0.838 and 0.842, respectively. The Kendall's coordination coefficients were 0.125, 0.094 and 0.135, respectively. After three rounds of expert correspondence, a quality evaluation index system of "Internet+ Obstetrical Nursing Service" was finally established, including 3 first-level indicators, 11 second-level indicators and 64 third-level indicators.Conclusions:The quality evaluation index system of "Internet+ Obstetrical Nursing Service" constructed in this study has good scientificity, reliability and operability. Experts have a high degree of agreement on the evaluation results of the index, which can provide reference for the standardization of "Internet+ Obstetrical Nursing Service".

Objective:To construct the "Internet +" nurse core competency evaluation index system.Methods:Combined with the policy analysis and literature research, a preliminary item pool was formed. The semi-structured interview was conducted to form a preliminary "Internet+" nurse core competency evaluation index system. From June to August 2021, the Delphi method was used to conduct three rounds of consultation with 19 experts, and finally determine the contents of the index system. The weights of indicators at all levels were calculated in combination with analytic hierarchy process.Results:Among three rounds of expert consultation, the questionnaire recovery rates were 100%, 100%, and 94.7% respectively, and the expert authority coefficients were 0.862, 0.857, and 0.841, and the Kendall coefficients were 0.228, 0.296, and 0.295 with statistical differences ( P<0.001) . The finally established "Internet +" nurse core competency evaluation index system included 4 first-level indicators, 16 second-level indicators and 59 third-level indicators of professional knowledge, professional skills, comprehensive ability and personal characteristics. Conclusions:The constructed "Internet +" nurse core competency evaluation index system is reliable, scientific and practical, and can be used as a basis for evaluating "Internet +" nurses' service capabilities.