Chronic cerebral hypoperfusion (CCH) plays an important role in the occurrence and development of vascular dementia (VD). Recent studies have indicated that multiple stages of immune-inflammatory response are involved in the process of cerebral ischemia, drawing increasing attention to immune therapies for cerebral ischemia. This study aims to identify potential immune therapeutic targets for CCH using bioinformatics methods from an immunological perspective. We identified a total of 823 differentially expressed genes associated with CCH, and further screened for 9 core immune-related genes, namely RASGRP1, FGF12, SEMA7A, PAK6, EDN3, BPHL, FCGRT, HSPA1B and MLNR. Gene enrichment analysis showed that core genes were mainly involved in biological functions such as cell growth, neural projection extension, and mesenchymal stem cell migration. Biological signaling pathway analysis indicated that core genes were mainly involved in the regulation of T cell receptor, Ras and MAPK signaling pathways. Through LASSO regression, we identified RASGRP1 and BPHL as key immune-related core genes. Additionally, by integrating differential miRNAs and the miRwalk database, we identified miR-216b-5p as a key immune-related miRNA that regulates RASGRP1. In summary, the predicted miR-216b-5p/ RASGRP1 signaling pathway plays a significant role in immune regulation during CCH, which may provide new targets for immune therapy in CCH.
Humans ; Computational Biology/methods* ; Brain Ischemia/therapy* ; Immunotherapy ; MicroRNAs/genetics* ; Signal Transduction ; Dementia, Vascular/genetics* ; Chronic Disease

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Bacterial biofilms(BF)are complex microbial communities formed by bacteria on living or abiotic surfaces.Their formation significantly enhances bacterial virulence and drug resistance and is associated with a high proportion of chronic bacterial infections,posing a serious threat to human health.The ability of traditional antibiotics and commonly used disinfectants to clear biofilms is limited,and an effective new strategy to treat BF is urgently needed.Bacteriophage,as a kind of virus that can infect and lyse bacteria,has high safety and specificity,and is considered as a promising alternative method for the treatment of BF.In this paper,the mechanism of bacteriophage anti-bacterial biofilm and the application strategies based on bacteriophage and its derivatives in the prevention and control of bacteriophage biofilm formation were reviewed,which provided new ideas for the development of efficient bacteriophage anti-bacterial biofilm methods.

Objective To establish a Nomogram model for assessing the risk of intestinal colonization by Carbapenem-Resistant Klebsiella pneumoniae(CRKP)to determine the specific probability of colonization and adopt individualized prevention strategies for the purpose of reducing the occurrence of colonization and secondary infection of neonatal CRKP.Methods A total of 187 neonates hospitalized between January 2021 and October 2022 and diagnosed with CRKP colonization by rectal swab/fecal culture as well drug sensitivity identification 48 h after admission were assigned to the CRKP group.Another 187 neonates without non-CRKP colonization during the same period were set as the non-CRKP group.All the data of the two groups were used for a retrospective analysis.The caret package in R 4.2.1 was used to randomly divide the 374 cases into the model group and validation group at a ratio of 3∶1.Then the glmnet package in R 4.2.1 was used to conduct a LASSO regression analysis over the data from the model group to determine the predictive factors for modeling and the rms software package was used to build a Nomogram model.The pROC and rms packages in R 4.2.1 were used to examine the data,analyzing the consistency indexes(Cindex),receiver operating characteristic curves(ROC),and area under the curves(AUC)and performing the internal and external validation of the efficacy of the Nomogram model via the calibration curves.Results LASSO regression analysis determined eight predictors from the 35 factors probably affecting neonatal CRKP colonization:gender,cesarean section,breastfeeding,nasogastric tube,enema,carbapenems,probiotics,and hospital stay.The Nomogram model constructed using these eight predictors as variables could predict CRKP colonization to a moderate extent,with the area under the ROC curve of 0.835 and 0.800 in the model and validation group,respectively.The Hos-mer-Lemeshow test showed that the predicted probability was highly consistent with the actual probability(the modeling group:P = 0.678>0.05;the validation group:P = 0.208>0.05),presenting a higher degree of fitting.Conclusion The Nomogram model containing such variables as gender,cesarean section,breastfeeding,nasogastric tube,enema,carbapenems,probiotics,and hospital stay is more effective in predicting the risk of neonatal CRKP colonization.Therefore,preventive measures should be individualized based on the colonization probability predicted by the Nomogram model in order to keep neonates from CRKP colonization and reduce the incidence of secondary CRKP infections among them.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective To analyze the influencing factors for intestinal colonization and secondary infection of car-bapenem-resistant Klebsiella pneumoniae(CRKP)in neonates,and provide a basis for formulating prevention and control strategies for CRKP infection.Methods Neonates who were admitted to the neonatal ward of a hospital from January 2021 to October 2022 were selected as the study subjects,and the first screening of CRKP was con-ducted within 48 hours after admission.In addition,active anal swab screening for carbapenem-resistant Ente-robacterales(CRE)was performed weekly during hospitalization,and the infection status of CRKP strains was mo-nitored.Clinical data of neonates in the colonization group,non-colonization group,and infection group were ana-lyzed.Intestinal colonized strains and the non-repetitive CRKP strains isolated from clinical specimens of neonates with secondary infection after colonization were performed carbapenemase gene detection,multilocus sequence ty-ping(MLST)and pulsed-field gel electrophoresis(PFGE)analysis.Results A total of 1 438 neonates were active-ly screened for CRE,174 were CRKP positive,CRKP colonization rate was 12.1％.Among 174 neonates,35 were with secondary infection,with the incidence of 20.1％.The independent risk factors for neonatal CRKP intestinal colonization were cesarean section(OR=2.050,95％CI:1.200-3.504,P=0.009),use of cephalosporins(OR=1.889,95％CI:1.086-3.288,P=0.024),nasogastric tube feeding(OR=2.317,95％CI:1.155-4.647,P=0.018).Protective factors were breast-feeding(OR=0.506,95％CI:0.284-0.901,P=0.021),oral probiotics(OR=0.307,95％CI:0.147-0.643,P=0.002),and enema(OR=0.334,95％CI:0.171-0.656,P=0.001).Independent risk factors for secondary infection after intestinal colonization of neonatal CRKP were carbapenem anti-biotic use(OR=19.869,95％CI:1.778-222.029,P=0.015)and prolonged hospital stay(OR=1.118,95％CI:1.082-1.157,P＜0.001).The detection results of drug resistance genes showed that carbapenemase-producing genes of CRKP strains were all blaKPC-2,all belonged to type ST11.Homologous analysis showed that intestinal CRKP colonization was highly homologous with the secondary infection strains after colonization.Conclusion CRKP intestinal colonization during neonatal hospitalization may increase the risk of CRKP infection.Risk and pro-tective factors of neonatal intestinal colonization and secondary infections after colonization should be paid attention,and corresponding preventive and control measures should be taken,so as to reduce the occurrence and transmission CRKP healthcare-associated infection.

Abstract Prevention and control of myopia requires comprehensive measures. Based on the system established earlier, the system is revised and upgraded. The original system emphasizes comprehensive measures and proposes to focus on both the symptoms and root causes. These measures are summarized into six aspects, three address the root cause measures including health education, glasses optics and visual environment, and three address symptoms measures including eye exercises, physical therapy and drugs. The paper is comprehensively supplemented and analyzes the primary and the secondary, and promotes physical therapy from treating the symptoms to treat both the symptoms and the root causes. These improvement measures will help promote the prevention and control of myopia in children and adolescents.

Objective: To examine the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression among healthcare workers, so as to provide the reference for developing effective psychological intervention. Methods: The clinical doctors, nurses and public health professionals were selected using the stratified random cluster sampling method from hospitals, disease prevention and control centers, and health departments in five cities in Shandong Province, including Qingdao, Jinan, Rizhao, Jining and Liaocheng in January 2023. Basic information, mindfulness level, resilience and symptoms of anxiety and depression among healthcare workers were collected using general demographic questionnaires, the 5-item Mindful Attention Awareness Scale, 10-item Connor-Davidson Resilience Scale, Generalized Anxiety Disorder Scale and Patient Health Questionnaire, respectively. The Process program was used to analyze the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression. Results: A total of 1 836 healthcare workers were investigated, including 472 males (25.71%) and 1 364 females (74.29%), and the median age was 39 (interquartile range, 12) years. There were 629 clinical doctors (34.26%), 963 nurses (52.45%) and 244 public health professionals (13.29%). The median scores of mindfulness level and resilience were 22 (interquartile range, 7) and 20 (interquartile range, 4) points, respectively. The detection rates of anxiety and depression symptoms were 49.78% and 72.28%, respectively. The mediation analysis showed that mindfulness level exerted a partial mediating effect between resilience and anxiety symptoms (β=-0.510, P<0.001), with a direct effect value of -0.130 and a mediating effect value of -0.046, and the mediating effect accounted for 26.14% of the total effect; mindfulness level also exerted a partial mediating effect between resilience and depression symptoms (β=-0.575, P<0.001), with a direct effect value of -0.120 and a mediating effect value of -0.052, and the mediating effect accounted for 30.23% of the total effect. Conclusion Mindfulness level plays a mediating effect between resilience and symptoms of anxiety and depression among healthcare workers.