BACKGROUND: Reports regarding adipose-derived stern cells (ADSCs) differentiation into dopaminergic (DN) neurons are few in addition, there is not experimental evidence of the effect of ADSCs on maintaining the survival of DN neurons.OBJECTIVE: To investigate the effect of glial cell-derived neurokophic factor (GDNF)-modified adipose-derived stem cells on survival of DN neurons under co-cultured condition.DESIGN, TIME AND SETrlNG: The in vitro cytology experiment was conducted at the Institute of Otolaryngology-Head and Neck Surgery and Key Laboratory of Zoonoses of Ministry of Education between March and December 2007.MATERIALS: Wistar rats with 3-weeks-old, or 14 days of pregnancy were provided by Norman Bethune College of Medicine, Jilin University.METHODS: The GDNF recombinant adenovirus was constructed by using pAdTrackCMV and pAdEasy-1 system. DN neurons were obtained from the rostral mesencaphalic tegmentum of Wistar rat embryos by using trypsin and collagenase method. ADSCs isolated from rat inguinal fat pads were digested with collagenase Ⅱ, cultured and passaged in vitro. When the cells reached 60% cenfluency at the 3rd passage, cells were transfectad with 1×109vp/mL of Ad-GDNF for 1 hour and then transferred into growth medium for another 24 hours, and GDNF level in cell supematant was detected by ELISA assay. Meanwhile, the co-cultured of ADSCs and DN neurons were carried out for following 7 days. With GFP-modified ADSCs was served as a control group.MAIN OUTCOME MEASURES: The effect of co-cultured condition on the survival of DN neurons, as well as the differentiation of GDNF-modified ADSCs was detected by immunofluorescence staining.RESULTS: GDNF appeared in ADSCs supematant at 24 hours after Ad-GDNF transfection and reached a peak at 72 hours.There was approximately 80% GFP-positive labeled in ADSCs. The tyrosinase hydroxylase staining results demonstrated that the rate of survival DN neurons were significantly increased than in DA neurons cultured alone, co-cultured group of GFP-modified ADSCs and GDNF-modified ADSCs groups (55%, 15%, 25%, P < 0.01). However, there were no co-expressing TH and GFP positive cells appeared at 7 days of co-culture, which indicated that the co-cultured condition was not available to ADSCs differentiation.CONCLUSION: The co-cultured of GDNF modified ADSCs and DN neurons can promote the survival and growth of cultured DN neurons, however, it can not induce ADSCs differentiate into DN neurons.

Objective:To explore whether tryptophan metabolism is related to bone growth by comparing the differences in tryptophan metabolism after rotator cuff tear (RCT) repair between rats with normal bone remodeling capability and those with defective bone remodeling capability.Methods:Of the 50 adult female Sprague Dawley (SD) rats used for this study, 18 were randomly selected to undergo bilateral ovariectomy (OVX) (OVX group), and the remaining 32 underwent bilateral OVX sham surgery (sham surgery group). All rats were maintained in standard conditions. Three months after surgery, 4 rats were randomly selected from OVX group and the sham surgery group, respectively, for Micro CT identification of bone loss at the rat humeral head. The remaining rats in OVX group underwent RCT modeling and surgical repair of acute supraspinatus muscle transection (OVX+RCT group) ( n=14); the remaining rats in the sham surgery group were subjected to either surgical repair of acute supraspinatus muscle transection (RCT group, n=14) or RCT sham surgery (SO group, n=14). The grip power of the rats was tested 2 weeks after surgery. The supraspinatus tendon-bone complex was harvested for evaluation of new bone formation and growth through real-time fluorescence quantitative polymerase chain reaction (qPCR), hematoxylin eosin (HE) staining, and immunohistochemistry (IHC) staining. The tryptophan metabolism was analyzed using ultra high performance liquid chromatography (UPLC). Results:The grip power test showed that SO group had the greatest grip power, followed by RCT group and OVX+RCT group, with statistically significant differences between the 3 groups ( P<0.05). The qPCR showed that the relative expression of osteosclerosis in the tendon-bone complex in SO group was significantly higher than that in OVX+RCT group and RCT group; IHC staining showed that the relative expression of osteocalcin in RCT group was significantly higher than that in SO group and OVX+RCT group ( P<0.05). The UPLC showed that the content of tryptophan in the rotator cuff tendon-bone complex was similar among SO, RCT, and OVX+RCT groups, showing no significant difference ( P>0.05). The qPCR showed that the expression of indoleamine 2, 3-dioxygenase 2 in the Kynurenic acid metabolism pathway showed an increasing trend from SO group to RCT group to OVX+RCT group, with OVX+RCT group significantly higher than SO group ( P<0.05). The expression of 3-hydroxybenzoate 3, 4-dioxygenase in OVX+RCT group was significantly higher than that in RCT group and in SO group ( P<0.001). The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased from SO group to RCT group to OVX+RCT group. The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased among SO, RCT, and OVX+RCT groups( P<0.001). The expression of dopamine decarboxylase in the indole metabolism pathway in OVX+RCT group was significantly higher than that in SO group ( P<0.01). The expression of cytochrome P450 oxidoreductase increased from SO group to RCT group to OVX+RCT group ( P<0.001). Conclusions:The tryptophan metabolism in the supraspinatus tendon-bone complex after RCT in rats is mainly dominated by kynurenic acid metabolism, followed by 5-hydroxytryptamine metabolism. In RCT bone remodeling, the 5-hydroxytryptamine metabolic pathway changes the most, followed by the indole pathway. The contents of niacin and xanthurenic acid in the kynurenic acid metabolism pathway are related to bone growth; the 5-hydroxytryptamine, hydroxyindoleacetic acid, and melatonin in the 5-hydroxytryptophan metabolic pathway are related to bone growth; the tryptophan and indole lactate in the indole metabolism pathway are related to bone growth. Therefore, tryptophan metabolism is related to bone growth, providing potential therapeutic targets for RCT repair.

The pathogenesis of stroke is complex, with genetic risk factors as one of the main factors. The genetic variants of phosphodiesterase 4D (PDE4D) was significantly associated with the susceptibility to ischemic stroke (IS) in Caucasian population, but its association with the susceptibility to stroke in Chinese population is unclear. This article is intended to review the research on the association between PDE4D genetic variants and stroke susceptibility in Chinese population, aiming to further optimize the relevant research programs and provide reference for the prevention and treatment of stroke in China.
Humans ; Brain Ischemia/genetics* ; Genetic Predisposition to Disease ; East Asian People ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics* ; Stroke/genetics* ; Polymorphism, Single Nucleotide ; Risk Factors

Objective To investigate the diagnostic value of immunophenotype in distinguishing acute promyelocytic leukemia(APL)from HLA-DR negative acute myeloid leukemia(AML)using flow cytometry.Methods A retrospective observational study was con-ducted including 42 APL patients and 28 newly diagnosed or relapsed HLA-DR negative AML patients admitted to our hospital from 2014 to 2024.Immunophenotype analysis was performed on bone marrow aspirate samples using flow cytometry.The positive expression rates of CD64,MPO,CD7,CD11c,CD9,CD123 and other antigens were compared between the two groups using the Chi-square test.The diagnostic efficiency of the CD9/123 and CD64+MPO+CD7 CD11c-models for APL was evaluated using receiver operating charac-teristic(ROC)curves.Results The HLA-DR negative AML group exhibited significantly lower positive rates of CD64,CD9 and MPO(P＜0.05),and higher positive rates of CD11c and CD7(P＜0.05)compared to APL group.The CD64+MPO+CD7-CD11c-model had an area under the curve(AUCROC)of 0.859,sensitivity of 93.8％and specificity of 75.0％for distinguishing APL.The CD9/CD123 expression pattern had AUCROC of 0.919,sensitivity of 83.3％and specificity of 84.0％for APL diagnosis.The combined CD9/123 and CD64+MPO+CD7-CD11c-model had AUCROC of 0.955,sensitivity of 83.3％and specificity of 100％.Conclusion The combined CD9/123 and CD64+MPO+CD7-CD11c-expression pattern may serve as a helpful tool for differentiating APL from HLA-DR negative AML.

Objective:To summarize and analyze the real experience of conscious patients in Intensive Care Unit (ICU) during hospitalization.Methods:Qualitative researches on the real experience of conscious patients in ICU during hospitalization were searched through computer on China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc, PubMed, Embase, Web of Science, CINAHL, Cochrane Library and so on. The search period was from the establishment of the database to April 30, 2022. The quality evaluation was conducted using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center in Australia. The aggregation integration method was used to summarize and integrate the results.Results:A total of 12 articles were included, and 54 results were extracted and categorized into 11 categories. Four integrated outcomes were formed, including physiological discomfort, psychological discomfort, desire for support, active response and self-reflection.Conclusions:ICU conscious patients experience severe physiological and psychological discomfort during hospitalization. While patients themselves actively respond, medical and nursing staff should further provide high-quality nursing care and psychological counseling to patients, optimize their support system, improve the hospitalization experience of ICU patients, and promote disease recovery.

Objective:To systematically synthesize qualitative research on the emotional experience of fathers of premature infants hospitalized in neonatal intensive care unit (NICU), so as to provide a basis for the care guidance and psychological care of fathers of premature infants.Methods:The articles on the qualitative study of emotional experience of fathers of premature infants in NICU were systematically searched through computers in PubMed, Embase, Web of Science, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Medline Disc. The search period was from the establishment of the database to May 15, 2022. The article quality evaluation was conducted using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center in Australia. The aggregation integration method was used to summarize and synthesize the results.Results:A total of 9 articles were included, 33 research results were extracted, summarized into 9 categories, and ultimately integrated into 3 synthesized results, namely facing multiple pressures and challenges, craving support, actively responding and reflecting on growth.Conclusions:The fathers of NICU premature infants have heavy physical and mental burdens, and hope to receive support from multiple parties. It is recommended that medical and nursing staff pay attention to the inner experiences and needs of fathers of NICU premature infants, optimize the support system, and improve their coping ability and promote their mental health.

Objective To explore the application value of RMNES combined with comprehensive rehabilitation for consciousness impairment caused by senile brain injury.Methods A retrospec-tive analysis was conducted on 160 elderly patients with consciousness disorders caused by brain injury admitted in our hospital between January 2020 and November 2023.According to treatment regiments,they were divided into comprehensive rehabilitation group(Group Ⅰ,53 cases),com-prehensive rehabilitation followed by RMNES group(Group Ⅱ,54 patients),and simultaneous indoor comprehensive rehabilitation and RMNES(Group Ⅲ,53 patients).At 1 week after treat-ment,electroencephalogram(EEG)grade,brainstem auditory induction(BAEP)grade,cerebral hemodynamic parameters[including relative cerebral blood flow(rCBF),relative cerebral blood volume(rCBV),and mean blood flow velocity(Vm)],Disability Rating Scale(DRS)score,and Glasgow Coma Scale(GCS)score were compared among the three groups.Results After 1 week of treatment,the ratios of EEG grade Ⅰ,EEG grade Ⅱ and BAEP grade Ⅰ,rCBV,rCBF and Vm values and GCS score were increased,while the ratios of EEG grade V and BAEP grade Ⅲ,and DRS score were decreased when compared with the levels before treatment(P＜0.05).Significant differences were observed in EEG grade and BAEP grade among the 3 groups after 1 week of treatment(P＜0.01);Group Ⅲ had obviously higher rCBV,rCBF,Vm and GCS score and lower DRS score than Groups Ⅰ and Ⅱ(P＜0.05).There was no statistical difference in the incidence of adverse reactions in Groups Ⅰ,Ⅱ and Ⅲ(3.77％vs 7.41％vs 7.55％,x2=0.830,P=0.660).Conclusion Simultaneous indoor comprehensive rehabilitation and RMNES treatment achieves more significant efficacy for elderly patients with brain injury-caused consciousness disorders,and it can improve electrophysiological activities of brain nerves,enhance cerebral hemodynamics,and promote the recovery of consciousness.

Objective:To investigate the behavioral problems of children with congenital adrenal hyperplasia (CAH), and to explore the influencing factors, thus providing evidence for their prevention and interventions.Methods:A case-control study was carried out.A total of 25 children with CAH who were aged 4-16 and regularly followed up in the Outpatient Department of the Second Xiangya Hospital, Central South University from June 1, 2017 to March 31, 2019 were enrolled in the study group, and 50 age-and gender-matched healthy children in Hunan Province were selected as the healthy control group.The parents of the selected subjects were investigated with the Achenbach Child Behavior Checklist (CBCL) to evaluate children′s behavior problems.SPSS 22.0 software was applied to statistical analysis.Results:(1) The scores of externalizing behaviors, aggressive factors and behavior problems in 4-to 5-year-old male children in the CAH group were significantly higher than those in the healthy control group [(12.440±8.353) scores vs.(5.060±5.230) scores, (9.670±6.481) scores vs.(4.110±4.157) scores, (22.110±13.062) scores vs.(12.890±9.405) scores] ( t=2.829, 2.711, 2.109, respectively, all P<0.05). There was no significant difference in the scores of other behavior problems and influencing factors between the CAH group and the healthy control group (all P>0.05). (2) The influencing factor of behavioral problems was progesterone ( β=0.567). Testoste-rone not only was the influencing factor of externalizing and internalizing behaviors ( β=0.582, 0.497, respectively), but also affected the behavior of physical complaints, violation of discipline and social withdrawal ( β=0.735, 0.531 and 0.492, respectively). The factor influencing the schizoid behavior was the initial treatment age ( β=0.402). Conclusions:Four- to 5-year-old male children with CAH have behavioral problems, among which aggression and externalizing behaviors are more common.The increase of testosterone may cause the problems of internalizing and externalizing behaviors in children with CAH, and has a great impact on physical complaints, social withdrawal, and discipline violation.The increase of progesterone may lead to the behavior problems of the children.The older the initial treatment age, the more serious the schizoid behavior problem may be.

Novel model systems have provided powerful tools for the research of human biology. Despite of being widely used, the conventional research models could not precisely describe the human physiological phenomenon. Organoids are three-dimensional multicellular aggregates derived from stem cells or organ progenitors that could differentiate and self-organize to recapitulate some specific functionalities and architectures of their in vivo counterpart organs. Organoids can be used to simulate organogenesis because of their human origin. In addition, the genomic stability of organoids could be well maintained during long-term amplification in vitro. Moreover, organoids can be cryopreserved as a live biobank for high-throughput screening. Combinatorial use of organoids with other emerging technologies (e.g. gene editing, organ-on-a-chip and single-cell RNA sequencing) could overcome the bottlenecks of conventional models and provide valuable information for disease modelling, pharmaceutical research, precision medicine and regenerative medicine at the organ level. This review summarizes the classifications, characteristics, current applications, combined use with other technologies and future prospects of organoids.
Gene Editing ; Humans ; Models, Biological ; Organoids ; Regenerative Medicine ; Stem Cells

In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.