Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Objective : To investigate the effect of polystyrene microplastics(PS-MPs) on myocardial injury in mice and its molecular mechanism. Methods: A total of 60 male C57BL/6 mice were randomly divided into normal saline group, 0.1, 1, 10 mg/kg PS-MPs exposed group, and doxorubicin [5 mg/(kg·w)] group treated for 8 weeks. After treatment, we measured blood pressure, cardiac organ coefficient, cardiac histopathological changes, oxidative stress markers reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), 4-hydroxynonenal(4-HNE) and nuclear factor E2-related factor 2(Nrf2), serum centroid injury markers creatine kinase MB(CK-MB) and troponin(cTnT), ferroptosis marker recombinant glutathione peroxidase 4(GPX4), Recombinant solute carrier family 7(SLC7A11) as well as ferrous ions(Fe2+). Results : Compared with the negative control group, vacuolation, inflammatory infiltration and collagen fiber deposition were evident in the hearts of mice after PS exposure. The levels of myocardial injury markers CK-MB and cTnT significantly increased. Cardiac organ coefficient decreased, blood pressure increased, oxidative stress markers and ferroptosis markers increased. Conclusion PS-MPs exposure can induce oxidative stress and activate ferroptosis pathway, resulting in myocardial injury in mice.

Objective To investigate the effect of PCSK9 inhibitors on the level of inflammation and ven-tricular remodeling after PCI in ST-elevation acute myocardial infarction.Methods A total of 220 patients with acute ST-segment elevation myocardial infarction who received percutaneous coronary artery intervention in the Emergency Center of Qingdao Central Hospital from April 2021 to July 2023 were randomly divided into two groups,110 patients in the control group were treated with conventional treatment,and 110 patients in the PCSK9i group were treated with PCSK9 inhibitors on the basis of conventional treatment.Compared before and after treatment left ventricular endsystolic diameter(LVESD)and left ventricular ejection fraction(LVEF)and triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),total cholesterol(TC).C-reactive protein(CRP),interleukin 6(IL-6),tumor necrosis factor α(TNF-α).The incidence of major adverse cardiovascular events(MACE)(including myocardial infarction,recurrence of heart failure,malignant arrhythmia,and cardiovascular death)was compared.Results After 6 months of treatment and follow-up,LVEDD(mm),LVESD(mm),TG(mmol/L),TC(mmol/L),LDL-C(mmol/L),CRP(mg/L),TNF-α(pg/mL)and JL-6(ng/mL)after PCSK9i treatment were significantly lower than those in the control group,and the difference was statistically significant[(51.32±5.84)vs.(54.43±2.91);(34.88±2.69)vs.(36.96±3.19);(1.41±0.61)vs.(2.13±1.26);(3.53±1.06)vs.(3.98±0.93);(0.95±0.36)vs.(1.79±0.27);(5.18±1.92)vs.(7.69±2.61);(36.43±9.41)vs.(57.79±14.43);(17.4±0.68)vs.(28.55±8.92),All P<0.01],and the LVEF(%)and HDL-C(mmol/L)in the PCSK9i group were higher than patients in the control group,and the difference was statistically significant[(46.69±3.63)vs.(41.34±3.42),P<0.05,(1.35±0.29)vs.(1.29±0.27),P<0.01].The incidence of MACE events in the PCSK9i group was obviously lower than patients in the control group(5.2%vs.13.6%,P<0.05).Conclusion The application of PCSK9 inhibitors after PCI in patients with ST-segment elevation acute myocardial infarction can better reduce blood lipids,stabilize coronary plaque,reduce local and circula-tory inflammatory responses after myocardial infarction,improve ventricular adverse remodeling after myocardial infarction,inhibit ventricular remodeling,and reduce the total incidence of MACE,worthing promoting use.

Objective To assess the tear film stability and morphological characteristics of the tarsal gland in myopic children.Methods In this prospective descriptive study,myopic children who performed refractive examinations in the Pediatric Ophthalmology & Refraction Clinic,Jinan Mingshui Eye Hospital from November 2021 to November 2022 were in-cluded.An Ocular Surface Disease Index(OSDI)questionnaire survey was carried out;tear meniscus height(TMH),non-invasive first breakup time(NIf-BUT)and images of the tarsal glands were obtained by OCULUS Keratograph 5M compre-hensive ocular surface analyzer.In addition,the atrophy and tortuosity of tarsal glands were scored to analyze the tear film stability and clinical characteristics of tarsal glands in myopic children.Results A total of 48 myopic children(91 eyes)aged from 7 to 16(10.25±2.23)years were recruited,including 27 males(56.25％)and 21 females(43.75％).The aver-age TMH was(0.19±0.04)mm(95％CI:0.18-0.19)and the average NIf-BUT was(5.40±2.62)s(95％CI:4.90-5.94);the TMH was positively correlated with NIf-BUT(r=0.223,P=0.034).The tarsal gland atrophy score was 1(0,1).The tortuosity score of the upper and lower tarsal gland was 0(0,1)and 0(0,0),respectively,with a statistically significant difference(Z=3.692,P＜0.001).In all subjects,49 eyes(53.85％)had tarsal gland atrophy,and 37 eyes(40.66％)had tarsal gland tortuosity.There were significant differences in TMH and NIf-BUT between children aged＜12 years and children aged ≥12 years(both P＜0.05).There was a significant difference in TMH between children with an OSDI score＜13 and children with an OSDI score ≥ 13(t=2.305,P=0.026).There was a significant difference in NIf-BUT between mild and moderate myopia children(t=2.300,P=0.024);the spherical equivalent was positively correlated with NIf-BUT(r=0.283,P=0.023).Conclusion Children with mild to moderate myopia show low tear film stability and a certain proportion of abnormal morphology in tarsal glands.In addition to the refractive status of children,attention should also be paid to ocular surface health in the refraction clinic.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Adaptive design, with advantages such as dynamically adjusting trial plans, reducing resource waste, and improving trial efficiency, has broken through the competitive situation of new drug development and gradually met the needs of clinical research. In recent years, the use of adaptive design in platform trials as an innovative research model has added impetus to new drug development. This article outlines the research progress, contents and characteristics, common design types, statistical analysis, and case interpretation of adaptive design, and introduces the concept, types, and applications of adaptive platform trials, with the hope of providing scientific reference for further exploration of clinical trials and new drug development.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Background Schizophrenia patients are often accompanied by negative symptoms and severe cognitive impairment,but effective interventions intended to alleviate such condition are currently limited.Existing researches on group play therapy for schizophrenia is still in its initial stages,and such therapy has the potential to contribute to symptoms improvement.Objective To explore the efficacy of group play therapy on improving cognitive function and negative symptoms in hospitalized female patients with schizophrenia,so as to provide references for clinical intervention in such group.Methods This study involved 40 female patients with schizophrenia who received inpatient treatment at the Third People's Hospital of Fuyang from April 2022 to May 2023 as well as met the diagnostic criteria of the International Classification of Diseases,tenth edition(ICD-10).They were divided into study group(n=20)and control group(n=20)according to the random number table method.Both groups received routine treatment,and the study group received 10 sessions of group play therapy for 5 weeks on the basis.At baseline,Scale for Assessment of Positive Symptoms(SAPS),Scale for Assessment of Negative Symptoms(SANS),Self-rating Depression Scale(SDS),Nurses' Observation Scale for Inpatient Evaluation(NOSIE),and Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)were used for assessment.Post-therapy evaluation was conducted by using SAPS,SANS and RBANS.Patients' baseline SAPS scores,SANS scores,RBANS total scores,and various factor scores of RBANS were used as covariates,and covariance analysis was adopted to compare the scores of each scale between the two groups after treatment.Results A total of 39 patients went through the whole study.Results of covariance analysis showed that the SANS score of study group was lower than that of control group,while several scores of RBANS(including total score,immediate memory factor score,speech function factor score and attention factor score)were all higher than those in control group.Significant difference was observed between two groups in scores of both scales above(F=13.408,10.331,4.932,9.967,10.010,P<0.05 or 0.01).Conclusion Group play therapy may help improve negative symptoms and cognitive function in hospitalized female patients with schizophrenia.

OBJECTIVE To explore whether diterpenoid 12-deoxyphorbol-13-palmitate （DP） from Euphorbia fischeriana can exert anti-leukemia effects through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signal pathway， and to provide experimental evidence for developing it into a new anti-leukemia drug. METHODS Using LY294002 （PI3K specific inhibitor） as tool drug， the effects of 24 h DP treatment on the proliferation and apoptosis of human myeloid leukemia HL60 cells were detected by MTT method， Annexin Ⅴ-FITC/PI staining and AO-EB staining. ELISA method was used to detect lactic dehydrogenase （LDH） release and the activities of cysteinyl aspartate specific proteinase 3 （caspase-3） and caspase-9. The transcriptional level of caspase-3， caspase-9， forkhead box O3a （FoxO3a） and B cell lymphoma 2 interacting mediator of cell death （Bim） mRNA were detected by real-time quantitative polymerase chain reaction （qRT-PCR）. The protein expression of phosphorylated FoxO3a （p- FoxO3a） and phosphorylated Akt （p-Akt） were detected by Western blot method. The nuclear translocation of FoxO3a protein was detected by immunostaining combined with laser confocal microscopy. RESULTS 10 μmol/L DP and 10 μmol/L DP+LY294002 could inhibit the proliferation and induce the apoptosis of HL60 cells （P＜0.01）. After treatment of 5， 10， 20 μmol/L DP， HL60 cells showed typical morphological characteristics of apoptosis； DP could significantly increase the levels of LDH release and the activities of caspase-3 and caspase-9 （P＜0.05 or P＜0.01）， in dose-dependent manner. After treatment of 10 μmol/L DP and 10 μmol/L DP+LY294002， the transcriptional levels of caspase-3， caspase-9 and Bim mRNA were increased significantly （P＜0.05 or P＜0.01）， and transcriptional level of FoxO3a mRNA and protein expressions of p-FoxO3a and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. Nuclear translocation changes were observed in FoxO3a protein in 10 μmol/L DP+LY294002 group， and the change was more significant than that of LY294002 group. CONCLUSIONS DP can inhibit the proliferation and induce the apoptosis of HL60 cells via inhibiting PI3K/Akt signaling pathway.

OBJECTIVE: To review the application and research progress of artificial intelligence (AI) technology in trauma treatment. METHODS: The recent research literature on the application of AI and related technologies in trauma treatment was reviewed and summarized in terms of prehospital assistance, in-hospital emergency care, and post-traumatic stress disorder risk regression prediction, meanwhile, the development trend of AI technology in trauma treatment were outlooked. RESULTS: The AI technology can rapidly analyze and manage large amount of clinical data to help doctors identify patients' situation of trauma and predict the risk of possible complications more accurately. The application of AI technology in surgical assistance and robotic operations can achieve precise surgical plan and treatment, reduce surgical risks, and shorten the operation time, so as to improve the efficiency and long-term effectiveness of the trauma treatment. CONCLUSION There is a promising future for the application of AI technology in the trauma treatment. However, it is still in the stage of exploration and development, and there are many difficulties of historical data bias, application condition limitations, as well as ethical and moral issues need to be solved.
Humans ; Artificial Intelligence ; Operative Time ; Robotic Surgical Procedures ; Technology