ObjectiveTo analyze the characteristics and influencing factors of elderly hospitalized patients with carbapenem-resistant gram-negative bacillus (CRO) infection in the intensive care unit (ICU) of a gradeⅡ level A general hospital in Yangpu District of Shanghai, and to provide scientific basis for the prevention and control of hospital-acquired CRO infection in such hospitals. MethodsThe clinical data of elderly ICU patients (age ≥60 years) from January 2019 to December 2023 were retrospectively collected. A total of 122 cases with hospital-acquired CRO infection were used as the case group, and a total of 68 cases with carbapenem-sensitive gram-negative (CSO) infection were used as the control group. The clinical characteristics of the two groups were analyzed, and univariate analysis and logistic regression analysis were performed for screening for possible influencing factors on hospital-acquired CRO infection. ResultsThe main pathogens of CRO infection were carbapenem-resistant Acinetobacter baumannii (CRAB) (53 cases, 43.44%) and carbapenem-resistant Klebsiella pneumoniae (CRKP) (46 cases, 37.70%), and 17 patients (13.93%) had more than two types of CRO infection. Among the CRO infection, the main sites were lower respiratory tract infection (58 cases, 47.54%), ventilator-associated pneumonia (21 cases, 17.21%), and catheter-associated urinary tract infections (16 cases, 13.11%). The incidence rate of poor prognosis was higher in the CRO infection group (54.10%) than that in the CSO infection group (36.76%) (P=0.021). The results of univariate analysis showed that male, history of hospitalization within three months, chronic respiratory disease, hypoproteinemia, anemia, and history of invasive procedures prior to infection, including indwelling central venous catheter, invasive mechanical ventilation, urinary catheter, gastric tube placement and parenteral nutrition, in addition, heparin anticoagulation, the use of broad-spectrum penicillin, third-generation cephalosporins, fluoroquinolones, carbapenems, carbapenems combined with fluoroquinolones, carbapenems combined with glycopeptides, use of ≥3 antibiotics and long time of antibiotic use prior to infection were all associated with the CRO infection (P<0.05). The results of logistic regression analysis showed that use of carbapenems (OR=7.739, 95%CI: 2.226‒26.911), ≥3 types of antibiotics (OR=6.307, 95%CI: 1.674‒23.754), invasive mechanical ventilation (OR=4.082, 95%CI: 1.795‒9.281), urinary catheter (OR=3.554, 95%CI: 1.074‒11.758), and comorbid hypoproteinemia (OR=4.741, 95%CI: 2.039‒11.022) and diabetes (OR=3.245, 95%CI: 1.344‒7.839) were positively correlated with the risk of CRO infection. ConclusionConcurrent use of carbapenems with multiple other antibiotics, as well as the use of invasive mechanical ventilation, urinary catheter, and comorbid hypoproteinemia and diabetes, may be associated with an increased influencing of CRO infection. More attention should be paid to the prevention and control of infection in elderly patients with the above-mentioned risk factors, and active screening of drug-resistant bacteria should be strengthened. Besides, the rational use of broad-spectrum antibiotics such as carbapenems, avoiding unnecessary invasive operations, and paying attention to patient nutrition and blood glucose control all can reduce the incidence of CRO infection and help to improve clinical outcomes.

OBJECTIVE: To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer (NSCLC). METHODS: The target molecules of oridonin were retrieved from SEA, STITCH, SuperPred and TargetPred databases; target genes associated with the treatment of NSCLC were retrieved from GeneCards, DisGeNET and TTD databases. Then, the overlapping target molecules between the drug and the disease were identified. The protein-protein interaction (PPI) was constructed using the STRING database according to overlapping targets, and Cytoscape was used to screen for key targets. Molecular docking verification were performed using AutoDockTools and PyMOL software. Using the DAVID database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8, cell proliferation EdU image kit, and Annexin V-FITC/PI apoptosis kit respectively. Moreover, real-time quantitative PCR and Western blot were used to verify the potential mechanisms. RESULTS: Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified, including tumor protein 53 (TP53), Caspase-3, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase kinase 8 (MAPK8), and mammalian target of rapamycin (mTOR). Molecular docking showed that oridonin and its key target molecules bind spontaneously. GO and KEGG enrichment analyses revealed cancer, apoptosis, phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), and other signaling pathways. In vitro experiments showed that oridonin inhibited the proliferation, induced apoptosis, downregulated the expression of Bcl-2 and Akt, and upregulated the expression of Caspase-3. CONCLUSION Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC, and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.
Diterpenes, Kaurane/chemistry* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Network Pharmacology ; Lung Neoplasms/pathology* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Gene Expression Regulation, Neoplastic/drug effects* ; Reproducibility of Results ; Gene Ontology

Retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system (RAS), on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μmol/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/mL) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. Single-cell RNA sequencing (scRNA-seq) matrix data from the Gene Expression Omnibus (GEO) database and RAS-related genes from the Molecular Signatures Database (MSigDB) were sourced for subsequent analyses. By integrating scRNA-seq data across multiple species, we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch wound healing, and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α (HIF-1α)/VEGF pathway. Further, coincubation with D-Pro⁷ (Mas-related G protein-coupled receptor D (MrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway, providing a potential therapeutic agent for OIR prevention and treatment.
Animals ; Retinal Neovascularization/prevention & control* ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism* ; Humans ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Oligopeptides/therapeutic use* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Endothelial Cells/drug effects* ; Retinopathy of Prematurity/drug therapy* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Renin-Angiotensin System/drug effects* ; Cells, Cultured

ObjectiveTo analyze the data of hospitalized accidental injuries with registered residence in Yangpu District， Shanghai， to describe their characteristics， and to provide an evidence for formulating accidental injuries prevention and control strategies. MethodsStatistic analysis was conducted on the data of accidental hospitalized injury cases in Yangpu District. The incidence rate （per 100 000 population） and the hospital stay were used to analyze the characteristics of hospitalized accidental injuries. ResultsA total of 4 924 hospitalized accidental injury cases were reported in Yangpu District， Shanghai. The incidence rate was 468.77/10⁵， the ratio of male to female was 1∶1.41. Among them， the age ≥65 group had the highest incidence rate， accounting for 55.83% of all cases. The incidence rate of female was 1.97 times higher than that of male （χ²=287.61， P<0.05）. The top five causes of injuries were falls， traffic-related， accident blunt injuries， injury by sharp instrument and fire or burns. The incidence rate of falls in female was higher than in male （χ²=176.65， P<0.05）. The incidence rates of sharp instrument and blunt injuries in male were higher than in female（sharp instrument χ²=13.45， P<0.05； blunt injuries χ²=9.10， P<0.05）. Altogether， the incidence rates of falls and traffic-related accident increased with age group （falls χ²_trend=1 593.07， P<0.05； traffic related χ²_trend=106.82， P<0.05）. Fire or burns and drowning had a median length of hospital stay of 8 and 14 days， respectively. ConclusionFalls is the leading cause of hospitalized accidental injuries （accounting for about 74% of the total number of hospitalized accidental injury cases）， with a higher incidence rate among elderly people aged ≥65 years old， and higher female than in male. Although the incidence rates of burns and drowning are not high， the hospital stay is relatively long. Therefore， accidental injury prevention and intervention should be targeted at key accidental injuries （such as falls， fire or burns， and drowning） and key populations （such as elderly female aged ≥65 years old）， to reduce the likelihood and the related loss of accidental injuries.

Physiologically based pharmacokinetic (PBPK) models have been widely used to predict various stages of drug absorption, distribution, metabolism and excretion. Models based on machine learning (ML) and artificial intelligence (AI) can provide better ideas for the construction of PBPK models, which can accelerate the prediction speed and improve the prediction quality of PBPK. ML and AL can complement the advantages of PBPK model to accelerate the progress of drug research and development. This review introduces the application of machine learning and artificial intelligence in pharmacokinetics, summarizes the research progress of physiological pharmacokinetic models based on machine learning and artificial intelligence, and analyzes the limitations of machine learning and artificial intelligence applications and their application prospects and prospects.

OBJECTIVE: To review the advancement made in the understanding of valgus impacted proximal humeral fracture (PHF). METHODS: The domestic and foreign literature about the valgus impacted PHF was extensively reviewed and the definition, classification, pathological features, and treatment of valgus impacted PHFs were summarized. RESULTS: PHF with a neck shaft angle ≥160° is recognized as a valgus impacted PHF characterized by the preservation of the medial epiphyseal region of the humeral head, which contributes to maintenance of the medial periosteum's integrity after fracture and reduces the occurrence of avascular necrosis. Therefore, the valgus impacted PHF has a better prognosis when compared to other complex PHFs. The Neer classification designates it as a three- or four-part fracture, while the AO/Association for the Study of Internal Fixation (AO/ASIF) categorizes it as type C (C1.1). In the management of the valgus impacted PHF, the selection between conservative and surgical approaches is contingent upon the patient's age and the extent of fracture displacement. While conservative treatment offers the advantage of being non-invasive, it is accompanied by limitations such as the inability to achieve anatomical reduction and the potential for multiple complications. Surgical treatment includes open reduction combined with steel wire or locking plate and/or non-absorbable suture, transosseous suture technology, and shoulder replacement. Surgeons must adopt personalized treatment strategies for each patient with a valgus impacted PHF. Minimally invasive surgery helps to preserve blood supply to the humeral head, mitigate the likelihood of avascular necrosis, and reduce postoperative complications of bone and soft tissue. For elderly patients with severe comminuted and displaced fractures, osteoporosis, and unsuitable internal fixation, shoulder joint replacement is the best treatment option. CONCLUSION Currently, there has been some advancement in the classification, vascular supply, and management of valgus impacted PHF. Nevertheless, further research is imperative to assess the clinical safety, biomechanical stability, and indication of minimally invasive technology.
Aged ; Humans ; Bone Plates ; Bone Wires ; Fracture Fixation, Internal/adverse effects* ; Fractures, Comminuted/surgery* ; Humeral Fractures ; Osteonecrosis ; Retrospective Studies ; Shoulder Fractures/surgery* ; Treatment Outcome

As the incidence of chronic kidney disease (CKD) increases year by year, the number of patients with CKD is increasing year by year before or during pregnancy. Pregnancy management is increasingly important for patients with kidney disease, and women with CKD face a number of challenges during pregnancy, such as the risk of kidney disease progression, fetal growth restriction, the potential teratogenicity of medications, and an increased risk of complications such as preeclampsia and preterm birth. In order to ensure a good outcome for pregnant women and the fetus, it is necessary for multidisciplinary physicians in the department of nephrology, obstetrics, reproductive health and other departments to assess the risk of pregnancy in patients with CKD in a standardized manner, adjust medication in a timely manner, and closely monitor to detect maternal and fetal complications early, stabilize the patient′s condition, and determine the safest time for pregnancy and delivery.

OBJECTIVE: To summarize the characteristics of posterior coronal banana-shaped fragments and its research progress in treatment of intertrochanteric femoral fracture with cephalomedullary nail, provide valuable reference for clinical practice. METHODS: Relevant domestic and foreign literature was extensively reviewed to summarize the history, anatomical structure of posterior coronal banana-shaped fragments, and the need for reduction and fixation, the influence on the stability of cephalomedullary nail, and the remedies. RESULTS: The posterior coronal banana-shaped fragments refers to the second level fracture line of the intertrochanteric femoral fracture, involving four anatomical structures, namely, the posterior part of the greater trochanter, the intertrochanteric crest, the lesser trochanter, and the posteromedial cortex. With the wide application of three-dimensional-CT in clinical practice, the posterior coronal banana-shaped fragments were more comprehensively understood. According to whether the anterior extension of the fracture line affects the integrity of the lateral entry of the head and neck implant, the posterior coronal banana-shaped fragments can be divided into small and large ones, of which the large single banana-shaped fragment account for about 20% of the AO/Orthopaedic Trauma Association (AO/OTA) type A2 fractures. If the large fragment involving the posteromedial wall (lesser trochanter) will increase the difficulty of the medial cortical contact reduction; or involving the posterolateral wall and resulting in rupture of the entry portal (type A2.4), which will cause sagittal swing of the nail in the femoral marrow cavity, thereby affecting the stability of the nail. There is no effective technique for reduction and fixation of the banana-shaped fragment nowadays. However, the adverse effects of posterior coronal banana-shaped fragment can be compensated by improving the quality of fracture reduction and choosing high filling cephalomedullary nail. CONCLUSION The posterior coronal banana-shaped fragments can easily lead to the rupture of the entry portal of head-neck implants, cause the sagittal swing of the cephalomedulis nail, and then lead to the loss of fracture reduction and affect the treatment effect. Whether the entry portal rupture or not and its risk factors still need further clinical and basic research.
Humans ; Bone Nails ; Fracture Fixation, Intramedullary/methods* ; Hip Fractures/surgery* ; Tomography, X-Ray Computed

ObjectiveTo determine the trend in diabetes-related death and probability of premature mortality among residents in Yangpu District of Shanghai and provide evidence for the formulation of relevant intervention strategies. MethodsMortality and demographic data were collected among residents in Yangpu District of Shanghai from 2002 to 2020. Statistical analysis was conducted using chi-square test with SPSS 21.0 and Excel 2010. Joinpoint regression was used to determine annual percent change （APC）. The mortality was standardized by utilizing the world standard population in 2000. ResultsA total of 25 091 cases of diabetes-related deaths were reported in Yangpu District， Shanghai from 2002 to 2020. The average annual crude mortality of diabetes-related diseases was 122.10/10⁵， which was 116.13/10⁵ in males and 128.23/10⁵ in females. The difference between males and females in crude mortality was statistically significant （P<0.05）. Moreover， primary causes of diabetes-related deaths were diabetes， cardiovascular and cerebrovascular diseases， and tumors. Among diabetic deaths， peripheral circulatory complications accounted for 50.79%， followed by renal complications （16.05%）. The crude mortality in males， females， and total of diabetes-related diseases showed an upward trend， while the standardized mortality remained stable with an upward trend in male and a downward trend in female. Furthermore， the crude mortality in males， females， and total of diabetes complicated with cardiovascular and cerebrovascular diseases showed an increasing trend. In contrast， both the standardized mortality in males and in total showed an increasing trend， while that in females remained stable. The overall crude mortality of diabetes was on the rise， which was increasing in males and stable in females. The overall standard mortality of diabetes was on the decline， which was increasing in males while declining in females. In addition， the probability of premature mortality caused by diabetes-related diseases， cardiovascular and cerebrovascular diseases complicated with diabetes， and diabetes decreased from 2002 to 2020 with no statistical significance. Males showed an upward trend while females showed a downward trend. ConclusionThe mortality of diabetes-related diseases， cardiovascular and cerebrovascular diseases complicated with diabetes， and diabetes among residents in Yangpu District of Shanghai is on the rise. Similarly， standardized mortality and probability of premature mortality in males for all three diseases are also on the rise. It warrants more attention to the health of male diabetes patients and targeted measures to reduce the disease burden.