This paper aimed to systematically evaluate the effects of hypoxic training at different fraction of inspired oxygen (FiO₂) on body composition, glucose metabolism, and lipid metabolism in obese individuals, and to determine the optimal oxygen concentration range to provide scientific evidence for personalized and precise hypoxic exercise prescriptions. A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and CNKI databases for randomized controlled trials and pre-post intervention studies published up to March 31, 2025, involving hypoxic training interventions in obese populations. Meta-analysis was performed using RevMan 5.4 software to assess the effects of different fraction of inspired oxygen (FiO₂≤14% vs. FiO₂>14%) on BMI, body fat percentage, waist circumference, fasting blood glucose, insulin, HOMA-IR, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with subgroup analyses based on oxygen concentration. A total of 22 studies involving 292 participants were included. Meta-analysis showed that hypoxic training significantly reduced BMI (mean difference (MD)=-2.29,95%CI: -3.42 to -1.17, P<0.000 1), body fat percentage (MD=-2.32, 95%CI: -3.16 to -1.47, P<0.001), waist circumference (MD=-3.79, 95%CI: -6.73 to -0.85, P=0.01), fasting blood glucose (MD=-3.58, 95%CI: -6.23 to -0.93, P=0.008), insulin (MD=-1.60, 95%CI: -2.98 to -0.22, P=0.02), TG (MD=-0.18, 95%CI: -0.25 to -0.12, P<0.001), and LDL-C (MD=-0.25, 95%CI: -0.39 to -0.11, P=0.000 3). Greater improvements were observed under moderate hypoxic conditions with FiO₂>14%. Changes in HOMA-IR (MD=-0.74, 95%CI: -1.52 to 0.04,P=0.06) and HDL-C (MD=-0.09, 95%CI: -0.21 to 0.02, P=0.11) were not statistically significant. Hypoxic training can significantly improve body composition, glucose metabolism, and lipid metabolism indicators in obese individuals, with greater benefits observed under moderate hypoxia (FiO>14%). As a key parameter in hypoxic exercise interventions, the precise setting of oxygen concentration is crucial for optimizing intervention outcomes.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

As a microbial therapy method, fecal microbiota transplantation (FMT) has attracted the attention of researchers in recent years. As one of the most direct and effective methods to improve gut microbiota, FMT achieves therapeutic benefits by transplanting functional gut microbiota from healthy human feces into the intestines of patients to reconstruct new gut microbiota. FMT has been proven to be an effective treatment for gastrointestinal diseases such as Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel disease. In addition, the clinical and basic research of FMT outside the gastrointestinal system is also emerging. It is worth noting that there is bidirectional communication between the gut microbial community and the central nervous system (CNS) through the gut-brain axis. Some gut bacteria can synthesize and release neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and dopamine. Imbalanced gut microbiota may interfere with the normal levels of these neurotransmitters, thereby affecting brain function. Gut microbiota can also produce metabolites that may cross the blood-brain barrier and affect CNS function. FMT may affect the occurrence and development of CNS and its related diseases by reshaping the gut microbiota of patients through a variety of pathways such as nerves, immunity, and metabolites. This article introduces the development of FMT and the research status of FMT in China, and reviews the basic and clinical research of FMT in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neurotraumatic diseases (spinal cord injury, traumatic brain injury) and stroke from the characteristics of three types of nervous system diseases, the characteristics of intestinal flora, and the therapeutic effect and mechanism of fecal microbiota transplantation, summarize the common mechanism of fecal microbiota transplantation in the treatment of CNS diseases and the therapeutic targets. We found that the common mechanisms of FMT in the treatment of nervous system diseases may include the following 3 categories through summary and analysis. (1) Gut microbiota metabolites, such as SCFAs, TMAO and LPS. (2) Inflammatory factors and immune inflammatory pathways such as TLR-MyD88 and NF-κB. (3) Neurotransmitter 5-HT. In the process of reviewing the studies, we found the following problems. (1) In basic researches on the relationship between FMT and CNS diseases, there are relatively few studies involving the autonomic nervous system pathway. (2) Clinical trial studies have shown that FMT improves the severity of patients’ symptoms and may be a promising treatment for a variety of neurological diseases. (3) The improvement of clinical efficacy is closely related to the choice of donor, especially emphasizing that FMT from healthy and young donors may be the key to the improvement of neurological diseases. However, there are common challenges in current research on FMT, such as the scientific and rigorous design of FMT clinical trials, including whether antibiotics are used before transplantation or different antibiotics are used, as well as different FMT processes, different donors, different functional analysis methods of gut microbiota, and the duration of FMT effect. Besides, the safety of FMT should be better elucidated, especially weighing the relationship between the therapeutic benefits and potential risks of FMT carefully. It is worth mentioning that the clinical development of FMT even exceeds its basic research. Science and TIME rated FMT as one of the top 10 breakthroughs in the field of biomedicine in 2013. FMT therapy has great potential in the treatment of nervous system diseases, is expected to open up a new situation in the medical field, and may become an innovative weapon in the medical field.

The author analyzed the characteristics of phase Ⅰ clinical trials of macromolecular drugs,the characteristics of evaluation indicators of phase Ⅰ clinical trials of macromolecular drugs,such as safety evaluation,pharmacokinetic and pharmacodynamic evaluation,and efficacy evaluation.And the control points of subjects management,management of experimental macromolecule drugs,and identified and potential risk factors of macromolecule drugs in the implementation of risk management for phase Ⅰ clinical trials of macromolecule drugs were discussed in depth based on previous clinical trial research experience.Through discussion and analysis,the author suggests that each research center can formulate risk control strategies according to the actual situation,improve the efficiency of risk control,and facilitate the smooth implementation of clinical trials and improve the quality of clinical trials.

Objective:To develop a Pediatric Nursing Care Deficiency Scale (PNCDS) and evaluate its reliability and validity.Methods:Based on theories of nursing care deficiency and considering pediatric nursing characteristics, the scale was developed following standard procedures and principles. This included semi-structured interviews, expert evaluations, a pilot survey, and a large-scale survey to finalize the scale.Results:The final version of the PNCDS comprised four dimensions with 25 items. The content validity index (CVI) of the overall scale was 0.937, with item-level CVIs ranging from 0.857 to 1.000. Exploratory factor analysis revealed that the factor loadings for all items were greater than 0.5, and the four factors accounted for a cumulative variance of 66.456%. Confirmatory factor analysis indicated a good model fit for the final scale. The overall Cronbach's α coefficient for the scale was 0.917, while the Cronbach's α coefficients for the four dimensions were 0.861, 0.923, 0.881, and 0.909, respectively.Conclusions:The PNCDS demonstrated good reliability and validity and provides a useful tool for assessing pediatric nursing care deficiencies and aiding in the development of intervention strategies.

Objective:To explore the value of high frequency ultrasound scoring combined with serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) in evaluating the prognosis of neonatal respiratory distress syndrome (NRDS) in children.Methods:A total of 106 children with NRDS who were treated at Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University from March 2021 to December 2022 were selected. According to the discharge outcome, NRDS patients were divided into a poor prognosis group ( n=11) and a good prognosis group ( n=95), and the clinical data differences between the two groups were compared. At the same time, NRDS patients were divided into mild to moderate group ( n=75) and severe group ( n=31) based on the severity of the disease. The differences in high-frequency ultrasound scores of the lungs and serum levels of IL-6, CRP, and PCT were analyzed in children with different disease severity levels of NRDS. Logistic multiple regression analysis was used to identify the influencing factors of prognosis; receiver operating characteristic (ROC) curve analysis of lung high-frequency ultrasound score, IL-6, and their combination predicted the prognostic value of NRDS in children. Results:The gestational age, birth weight, and high-frequency ultrasound scores of the lungs in the poor prognosis group were significantly lower than those in the good prognosis group (all P<0.05); The proportion of diabetes in pregnancy, the proportion of severe disease, the first use time of pulmonary surfactant (PS) and the level of IL-6 in the poor prognosis group were significantly higher than those in the good prognosis group (all P<0.05). The serum levels of IL-6, CRP, and PCT in severe children were significantly higher than those in mild to moderate children (all P<0.05); The high-frequency ultrasound score of the lungs in severe children was significantly lower than that in mild to moderate children ( P<0.05). Logistic regression analysis showed that gestational age, pulmonary high-frequency ultrasound score, gestational diabetes, disease severity, and IL-6 were the influencing factors for poor prognosis of children with NRDS (all P<0.05). The area under the ROC curve for predicting poor prognosis in children with NRDS using high-frequency ultrasound score, IL-6, and their combination were 0.745, 0.802, and 0.786, respectively. Conclusions:The severity of NRDS in children is related to the high-frequency ultrasound score of the lungs and serum levels of IL-6, CRP, and PCT. At the same time, the high-frequency ultrasound score of the lungs and IL-6 are related to the prognosis of NRDS children, and have certain application value in predicting the prognosis of children.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective In order to shorten the transparency time of clear,unobstructed brain imaging cocktails and computational analysis(CUBIC),improve the transparency efficiency,and explore the possibility of applying hydrophilic tissue transparency technique,this study was conducted to optimize the perfusion of CUBIC technique and compare it with four hydrophilic tissue clearing method in terms of tissue transparency effect,transparency time,area change,volume change and adeno-associated virus(AAV)fluorescence retention.Methods Brain,liver,spleen and kidney of 6 adult Institute of Cancer Research(ICR)mice were subjected to clearing treatment by SeeDB,FRUIT,ScaleS and CUBIC method,respectively.The area and gray value of the samples were measured by Image J 1.8.0,and the volume before and after transparency was measured by drainage method to compare the transparency effect,time and size deformation of each group.Perfusion optimization of the CUBIC was performed by improving the perfusion rate with the optimal perfusion dose,each group of the experimental sample size was 6.Fluorescence preservation by different techniques was evaluated by injecting AAV in the motor cortex of 16 adult mice and taking the cervical spinal segments for transparency treatment after four weeks,and the fluorescence photographs were measured by Image J 1.8.0 to measure the mean fluorescent intensity.Results The optimal perfusion rate and dose of CUBIC was 15 ml/min and 200 ml respectively.For transparency ability and speed,the perfusion CUBIC had the lowest mean gray value and took the shortest time,while CUBIC consumed the longest time,and SeeDB,FRUIT,and ScaleS did not show good transparency ability.In terms of area and volume changes,several techniques showed different degrees of expansion after transparency of tissues or organs.In terms of fluorescence retention,perfusion CUBIC showed the best retention of green fluorescent protein(GFP)fluorescence signal,followed by CUBIC,ScaleS,FRUIT,and SeeDB.Conclusion Perfusion CUBIC technique shows the best tissue transparency,the shortest transparency time,and the most AAV fluorescence retention compared with other techniques.

Cancer therapy-related cardiovascular toxicity(CTR-CVT)is gradually becoming a critical factor affecting the prognosis of cancer survivors.Vascular endothelial growth factor(VEGF)and its receptor inhibitors(VEGFIs),developed as novel anti-cancer drugs targeting VEGF,are now widely used in clinical practice.They can extend the survival period of the cancer patients and improve the prognosis of the patients.However,the hypertension induced by VEGFIs,as the most common CTR-CVT,may limit and impact their use and leads to severe cardiovascular diseases(CVD).It is essential to closely monitor blood pressure in the cancer patients treated with VEGFIs,conduct early assessments,and optimize the management to achieve the best anti-cancer efficacy and minimize the risk of CTR-CVT.This review discusses the clinical manifestations,pathogenesis,diagnosis,and treatment strategies of VEGFIs-related hypertension,in order to provide better guidances for managing and addressing VEGFIs-related hypertension for the clinicians.

Lipoprotein(a)[Lp(a)]is a highly polymorphic lipoprotein molecule composed of apolipoprotein A(apo A),apo B100,and cholesterol ester core;calcific aortic valve stenosis(CAVS)is a multifactorial valvular heart disease influenced by both environmental and genetic factors.Lp(a)is an independent risk factor for CAVS and can increase the onset risk of CAVS.Lp(a)plays an important role in the treatment of CAVS.Although surgery is currently the main clinical treatment for CAVS,with further exploration into its pathological mechanism,drug therapy targeting Lp(a)has emerged as a new method.This paper reviews studies about the structure and characteristics of Lp(a),its role in the occurrence and development of CAVS,treatment options related to hyperlipoprotein Aemia,and the studies preventing and treating CAVS by combating inflammation,and enhances the clinicians'understanding and awareness of hyperlipoprotein Aemia and provides new insights for the prevention and targeted drug therapy of CAVS.