ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

ObjectivesTo explore the effect of diffuse glioma with precentral-gyrus invasion on fMRI activation maps by grasping T-fMRI. MethodsA total of 56 diffuse glioma patients were divided into precentral-gyrus invasion （PGI： n=21） and precentral-gyrus non-invasion （PGNI： n=35） groups. Three statistical thresholds （P value： 10^-4， P1； 10^-6， P2； 10^-8， P3） were set to obtain the activation maps accordingly （V1， V2 and V3）. The interhemispheric and bilateral precentral gyrus activation volumes ratios （IAVR and PAVR） were calculated， respectively. The activation volumes ［△V1=V1-V2； △V2=V2-V3； △Vn （ipsilateral）/△Vn’ （contralateral）， n=1， 2］ within two statistical thresholds and the corresponding interhemispheric ratio was further compared. In addition， the associations of tumor characteristics with IAVR and PAVR were analyzed. ResultsCompared with PGNI， PGI showed significantly decreased IAVR at p1， and the same trends of PAVR in PGI at P1 and P2 （P＜0.05）. However， neither IAVR nor PAVR showed significant differences at P3. PGI showed significantly lower ratios of △V1/△V1’ than PGNI （P=0.02）， except for △V2/△V2’. Additionally， within PGI， PAVR was negatively correlated with tumor volume （P=0.043）， and the distance from the tumor to the hand-knob was positively correlated with the IAVR and PAVR （P＜0.05）. ConclusionDiffuse glioma invading eloquent areas tended to affect interhemispheric asymmetry of activation at relatively lower statistical thresholds than diffuse glioma without invasion， rather than stricter statistical thresholds. Multiple ranges of statistical thresholds were recommended to analyze T-fMRI.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

China/epidemiology* ; Humans ; Pemphigoid, Bullous/epidemiology* ; Retrospective Studies

Objective:To explore the new generation of intelligent ICU Unit based on 5G and artificial intelligence technology.Methods:This study was conducted at the Second Affiliated Hospital, Zhejiang University School of Medicine from May 2019 to August 2020. Based on a multidisciplinary team including medical, nursing, hospital management, clinical medical engineering, 5G technology, information technology, artificial intelligence technology, logistics service, etc, was assembled to intelligently design and reconstruct an intelligent ICU Unit of Emergency ICU.Results:Based on 5G technology, a new intelligent ICU unit environment was constructed to realize remote and high-speed interaction of multi-dimensional information in ICU, including intelligent assistance of remote monitoring, remote ward rounds, remote consultation and family visits. An intelligent hospital infection prevention and control system was established including automatic identification and alarm of hand hygiene and personal protection.Conclusions:The new generation of intelligent ICU unit combined with 5G and artificial intelligence technology has changed the mode of medical service for critically ill patients and improved the service level, which is worthy of further exploration and application.

Objective:To better understand the clinical characteristics of children with pneumocystis pneumonia(PCP).Methods:Seven cases of non-human immunodeficiency virus infected children with PCP admitted to pediatric intensive care unit(PICU) at Xi′an Children′s Hospital from January 1, 2019 to December 31, 2019 were enrolled.Clinical findings, laboratory examination results, diagnosis, treatment, and outcome data were retrospectively reviewed.Results:There were seven children enrolled in this study including six boys and one girl.The average age was(6.09±3.80)years.Six patients received a long-term steroid or immunosuppressive therapy, and the average duration of medication was(80±30)days.One patient was eventually diagnosed with immunodeficiency disease despite no history of steroid and immunosuppressive therapy.Fever, cough and progressive dyspnea were the main manifestations.The pulmonary signs were not obvious, however, the chest radiographs showed serious ground glass changes.Laboratory examination showed that white blood cell counts were normal, lymphocyte counts were decreased to varying degrees, while C-reactive protein, calcitonin and lipopolysaccharide increased slightly or normal.Lactate dehydrogenase significantly increased and PaO 2/FiO 2 decreased, respectively.All children combined with different degrees of heart, liver and digestive tract damage.Pneumocystis jirovecii infection was diagnosed by metagenomics next-generation sequencing(mNGS), of which one case was detected by bronchoalveolar lavage fluid, and the remaining six cases were detected by peripheral blood.After entering PICU, mechanical ventilation, intravenous injection of human immunoglobulin, and continuous renal replacement therapy were performed.None of the children used TMP-SMZ for prophylaxis outside the hospital.Among them, one case was diagnosed with PCP before entering PICU and was given TMP-SMZ for 20 days, while the remaining six patients started to receive TMP-SMZ after entering PICU.Finally, one patient was cured, three died and another three cases died after giving up treatment.The average hospitalization days were(11.28±8.78)days, and the average hospitalization costs were (78, 000±24, 000) RMB. Conclusion:Children with non-human immunodeficiency virus infected PCP usually have underlying diseases or immunodeficiency diseases.Due to non-specific manifestations, rapid progression and high mortality, clinicians should pay more attention to it.It is necessary to dynamically observe the respiratory symptoms, perform mNGS as soon as possible, and give TMP-SMZ treatment in time.TMP-SMZ prophylaxis can be given to patients who are highly suspected of PCP but unable to perform pathogenic examinations.

Objective:To explore the application of metagenomics next generation sequencing(mNGS)in the immunosuppressed children with severe pneumonia and to understand the distribution of pathogens in order to provide reference for early prevention and treatment.Methods:We performed a retrospective analysis of the immunosuppressed children with severe pneumonia who had mNGS reports admitted to PICU according with the enrollment condition from July 2019 to July 2020.The records included general clinical data, traditional detection method report and mNGS results.We evaluated the consistency of the mNGS with the clinical microbiology reports and clinical judgment.Results:Twenty-three patients were enrolled, 15 were male and 8 were female, aging from 28 days to 10 years old, with an average age of(3.67±3.20)years old.Seven cases were cured, 2 were improved, and 14 died.A total of 23 samples were obtained, including 21 blood specimens and 2 bronchoal-veolar lavage fluid specimens.Among the 23 cases, 5 were single infected and 15 were mixed infected.Fungi were detected in 15 cases(65.22%), including 12 cases of Pneumocystis jirovecii, 2 cases of Aspergillus fumigatus and 2 cases of Candida albicans.Virus were detected in 14 cases(60.87%), including cytomegalovirus(CMV) in 10 cases(8 cases with pneumocystis infection), Herpes virus in 3 cases and fine ring virus in 2 cases(1 case with herpes virus infection). Bacteria were detected in 10 cases, including 3 cases of Acinetobacter, 1 case of Klebsiella pneumoniae, 1 case of Stenotrophomonas maltophilia, 1 case of Pinocytogenes, 4 cases of Staphylococcus and 1 case of Bacillus licheniformis.There were Mycoplasma in 3 cases with mixed infection.The positive rate and coincidence rate of mNGS were significantly higher than that of the traditional test group( P<0.05). A total of 19 cases were treated with hormone or immunosuppressive agents, and 17 cases were treated for 1 to 6 months when severe pneumonia occurred. Conclusion:Most immunosuppressed children with severe pneumonia are mixed infection.The common pathogens are Pneumocystis jirovecii and CMV.The use of mNGS can significantly improve the pathogen detection rate, effectively guiding the treatment.

Objective: To summarize the clinical characteristics of a patient with cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS) syndrome, followed by relative literature review. Methods: The medical history, physical examination and results of relative auxiliary examinations were collected from a CAPOS syndrome patient, who was definitely diagnosed by gene detection. Results: The patient was a 20-year-old male, complaining of poor coordination for 19 years, impaired vision for 15 years and hearing loss for 13 years. When he was eleven months old, weakness of four limbs happened after diarrhea but recovered spontaneously a few days later. Then his poor coordination was discovered. His vision has decreased progressively since the age of five and he began to suffer from bilateral hearing loss after fever at the age of seven. Anti-infectious and immunoregulatory treatment was ineffective at that time. Physical examination showed that bilateral visual acuity decreased. Transient horizontal gaze-evoked nystagmus and bilateral hearing loss were detected. Obvious shaking was observed with closed eyes and toes together. Finger-to-nose, finger tracking, heel-knee-tibia and alternate motion tests were slightly inaccurate. Deep tendon reflexes disappeared and no pes cavus was observed. Pure tone audiometry revealed bilateral sensorineural hearing loss. Cranial magnetic resonance imaging indicated bilateral optic atrophy. ATP1A3 gene detection in the patient showed c. 2452G>A (p. Glu818Lys) heterozygous mutation while his parents were detected no such mutation in the same locus. Conclusions As for young patients who suffer from acute cerebellar ataxia after fever, disappeared tendon reflexes, atrophy of optic nerves or sensorineural hearing loss, they should be alerted to CAPOS syndrome when immunomodulating or anti-inflammatory therapy has been proved to be useless. Positive family history and ATP1A3 gene mutation would be beneficial to definite diagnosis.

Objective: To analyze the genetic characteristics of a five generations pedigree with homozygous familial hypercholesterolemia (HoFH). Methods: Prospective study. Twenty family members included a proband diagnosed as familial hyperlipidemia at the cardiology Department of Xi′an Children′s Hospital in October 2018 were research object. Clinical data were collected. Genome DNAs were extracted. Whole exons sequencing was performed on the proband using target capture next generation sequencing. Candidate gene mutation sites identified by bioinformatics were verified by Sanger sequencing in the family members. The genotype-phenotype correlation of the pedigree was analyzed between heterozygous mutation carriers and non-carriers. Results: The proband was a 7-years and 10-month-old boy. He was born with a roundgreen bean size yellow skin protuberance in the skin of the coccyx. Since the age of 3-4 years old, xanthoma-like lesions with a diameter of 0.5-1.5 cm gradually appeared in the skin of bilateral elbow joints, knee joints and Achilles tendon. The height, weight and intellectual development of the child were the same as those of normal children at the same age. No similar xanthoma-like lesion was found in the other family members. The proband′s total cholesterol (TC) reached 18.16-21.24 mmol/L, and his low density lipoproteincholesterol (LDL-C) was 14.08-15.51 mmol/L. Carotid ultrasonography showed diffuse sclerotic plaques in bilateral carotid and vertebral arteries, and color Doppler echocardiography revealed aortic valve thickening and calcification. Gene testing identified that the proband carried a homozygous mutation C. 418G>A (p. E140K) in LDLR gene inherited from his parents who had a consanguineous marriage and carried a heterozygous mutation of LDLR-E140K, respectively.The TC, LDL-C and apolipoproteinB (ApoB) of LDLR-E140K gene heterozygous carriers ((8.40±0.13), (6.79±0.01) and (1.95±0.05) mmol/L, respectively) were significantly higher than those of non-carriers ((4.59±0.28), (3.35±0.39) and (0.86±0.10) mmol/L, t=7.269, 4.595, 6.311, respectively, P<0.05). Conclusions LDLR-E140K gene homozygous mutation is first reported to be associated with most severe phenotype HoFH. The genotype-phenotype analysis of the pedigree shows that the clinical phenotype of the proband with homozygous mutation is the most serious, and all the heterozygous mutation carriers present with hypercholesterolemia phenotype. The investigation confirms that LDLR-E140K is the pathogenic variation of familial hyperlipidemia.

The real-time training and mutual network system of stomatology is particularly suited for evaluating the clinical practice training process.This mutual system introduced the closed loop type mutual mode,which ensured the reliability of the evaluation in the practice teaching process by the mutual feedback between students and students,students and teachers.The system solved the deficiency of the previous open loop mutual systemand made the evaluation results more objective.The system realized the process control in practice teaching,and made progress in many ways such as improving the evaluation system of students' abilities,and promoting independent learning and feedback of the teaching.Through this system platform,the students make homework as a link to discover knowledge and further solve the problem.This system guides students to develop the abilities of independent learning and mutual learning,which combines students' mutual evaluation and teachers' evaluation,and shows teaching points comprehensively.The realtime training and mutual network system can explore an effective mean in the transformation education of stomatology,and further meet the new requirements of the social development.