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*

Aim To explore the potential mechanisms underlying therapeutic effects of cordycepin in asthma by utilizing network pharmacology,molecular docking,and in vitro cellular validation.Methods The thera-peutic targets associated with asthma and the drug tar-gets of cordycepin were systematically identified through comprehensive database searches.An overlap analysis of the two gene sets was performed,followed by the construction of a protein-protein interaction(PPI)network and topological analysis to identify the core targets.The core targets were subjected to Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway a-nalysis and Gene Ontology(GO)enrichment analysis,and a drug-target-pathway network was constructed.To validate the interaction between cordycepin and core targets,molecular docking and molecular dynamics sim-ulations were conducted.Subsequently,the pharmaco-logical effects and underlying mechanisms of cordyce-pin were validated in vitro using Beas-2B cells,emplo-ying Cell Counting Kit-8(CCK-8)assay and quantita-tive real-time reverse transcription PCR(RT-qPCR).Results A total of 438 potential targets of cordycepin were identified,113 of which overlapped with asthma-related therapeutic targets.Topological analysis based on the PPI network revealed 22 core targets.Using KEGG enrichment analysis,165 significantly enriched pathways were identified,including the TNF and HIF-1 signaling pathways.Molecular docking analysis re-vealed high binding affinities between cordycepin and select core targets,which further corroborated by mo-lecular dynamics simulations.In vitro experiments showed that after cordycepin pretreatment,the upregu-lation of MAPK1,HIF1A,MTOR,MYC,IL10,and JUN mRNA was significantly rescued in HDM-stimulated Beas-2B cells.Conclusions Cordycepin exerts anti-asthmatic effects by targeting MAPK1 and other key molecules,thereby providing a scientific foundation for its further development and clinical application.

Aim To explore the potential mechanisms underlying therapeutic effects of cordycepin in asthma by utilizing network pharmacology,molecular docking,and in vitro cellular validation.Methods The thera-peutic targets associated with asthma and the drug tar-gets of cordycepin were systematically identified through comprehensive database searches.An overlap analysis of the two gene sets was performed,followed by the construction of a protein-protein interaction(PPI)network and topological analysis to identify the core targets.The core targets were subjected to Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway a-nalysis and Gene Ontology(GO)enrichment analysis,and a drug-target-pathway network was constructed.To validate the interaction between cordycepin and core targets,molecular docking and molecular dynamics sim-ulations were conducted.Subsequently,the pharmaco-logical effects and underlying mechanisms of cordyce-pin were validated in vitro using Beas-2B cells,emplo-ying Cell Counting Kit-8(CCK-8)assay and quantita-tive real-time reverse transcription PCR(RT-qPCR).Results A total of 438 potential targets of cordycepin were identified,113 of which overlapped with asthma-related therapeutic targets.Topological analysis based on the PPI network revealed 22 core targets.Using KEGG enrichment analysis,165 significantly enriched pathways were identified,including the TNF and HIF-1 signaling pathways.Molecular docking analysis re-vealed high binding affinities between cordycepin and select core targets,which further corroborated by mo-lecular dynamics simulations.In vitro experiments showed that after cordycepin pretreatment,the upregu-lation of MAPK1,HIF1A,MTOR,MYC,IL10,and JUN mRNA was significantly rescued in HDM-stimulated Beas-2B cells.Conclusions Cordycepin exerts anti-asthmatic effects by targeting MAPK1 and other key molecules,thereby providing a scientific foundation for its further development and clinical application.

AIM:To observe how total flavonoids of Pterocarya hupehensis Skan(PHSTF)affects the migra-tion and invasion of human rheumatoid fibroblast-like synoviocyte line MH7A.METHODS:The MH7A cells were divided into control group(without any treatment),low-,medium-and high-dose(6.25,12.5 and 25 mg/L,respectively)PHSTF groups,phosphatidylinositol 3-kinase(PI3K)inhibitor 740Y-P(10 μmol/L)group,and 740Y-P(10 μmol/L)+high-dose(25 mg/L)PHSTF group.The viability of the MH7A cells was determined by CCK-8 assay,while the migration and inva-sion were assessed by scratch and Transwell assays.The protein levels of matrix metalloproteinase-2(MMP-2),MMP-9,PI3K,p-PI3K,AKT and p-AKT were detected by Western blot.RESULTS:Compared with control group,the cell via-bility in PHSTF treatment groups was reduced(P<0.05),the cell wound healing area was significantly decreased(P<0.01),migratory and invasive cells in the lower chamber were significantly reduced(P<0.01),and the protein expres-sion of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT were decreased(P<0.01).Compared with high-dose PHSTF group,the addition of PI3K/AKT pathway agonist 740Y-P significantly increased the migration and invasion ability of MH7A cells(P<0.01)and elevated the protein expression of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT(P<0.01)under the treatment with PHSTF.CONCLUSION:Total flavonoids of Pterocarya hupehensis Skan could inhibit the migration and invasion of MH7A cells by regulating the PI3K/AKT signaling pathway.

We retrieved the data on sexual-health internet hospitals from the Baidu Search Engine and Apple and Android APP Stores between August 2018 and September 2022.With the specialized Sexual-Health Internet Hospital affiliated to SPPH as an exam-ple,we analyzed its framework and system.It fully displays the closed-loop of medical service system of"doctor-patient-medicine-insurance-delivery",provides the protection of patients'privacy,offers comprehensive services,and manifests the values of socializa-tion,instrumentalization and commercialization.The booming of the internet medical industry in China is driven by national policies,and the rapid-rising of specialized internet hospitals largely stems from the clearer requirements of the state for regulation compliance and operation supervision.Against the background of the global spread of COVID-19,which has been demonstrated with a significant correlation to sexual health,only further rational and standardized management can ensure safe and efficient development of sexual-health internet hospitals to satisfy various health needs.

In line with the significant changes in disease spectrum, the wound healing discipline in China has shown a good momentum of development from budding to rapid growth. At present, improving the connotation of disciplinary development determines the speed and quality of disciplinary development in the future. The characteristics of wound diseases determine that the wound healing discipline must have the following property: standardization, integration, and translation. Here is the initial introduction on the connotation of standardization, collaboration, and translation in clinical practice of wound healing discipline. Besides, the discussions on standardization, integration, and translation in the 13 th National Conference of Wound Repair (Healing) and Tissue Regeneration were summarized. It is expected that these achievements can be reflected and improved in the construction of the wound healing discipline in China.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

OBJECTIVE: To investigate the expression of ROBO3 in pediatric AML patients and explore its function on cell proliferation and apoptosis. METHODS: The expression of ROBO3 in pediatric AML patients at different treatment stage was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The relationship between the expression of ROBO3 and clinic pathological characteristics in newly diagnosed pediatric AML patients was analyzed. Moreover, the effects of ROBO3 on the proliferation and apoptosis of AML cell lines HL-60 and THP-1 were estimated by using CCK-8 and flow cytometry after transfection with ROBO3 siRNA. RESULTS: It was found that ROBO3 expression was significantly increased in most of newly diagnosed pediatric AML patients, especially in non-M3 subtype, younger patients (<10 years old), and high risk group, compared to corresponding controls. Furthermore, the expression level of ROBO3 was sharply decreased in patients who achieved complete remission. Targeting ROBO3 significantly inhibited AML cell proliferation, as well as increased apoptosis by ROBO3 siRNA transfection in vitro. CONCLUSION ROBO3 is differentially expressed within distinct subtypes of the pediatric AML patients, which suggested that ROBO3 may be a potential biomarker and a new therapeutic target for pediatric AML.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Child ; Humans ; Leukemia, Myeloid, Acute/genetics* ; MicroRNAs/genetics* ; RNA, Small Interfering ; Receptors, Cell Surface ; Sincalide

Objective:To evaluate the relationship between phosphorylation of Tau protein and apolipoprotein E (ApoE) containing 18 kDa fragments and investigate the mechanism of neuronal damage induced by sevoflurane.Methods:Primary neurons (ApoE3 and ApoE2 genotypes, 24 dishes for each genotype) of fetal mice cultured until the 5th day were divided into 4 groups ( n=12 each) using a random number table method: ApoE3 control group (A3C group), ApoE3 sevoflurane group (A3S group), ApoE2 control group (A2C group) and ApoE2 sevoflurane group (A2S group). Neurons were treated with 21% oxygen + 5% carbon dioxide + 4.1% sevoflurane for 4 h in A3S and A2S groups, while the neurons were only treated with 21% oxygen + 5% carbon dioxide in A3C and A2C groups.The cell proteins were then extracted to detect the expression of full-length ApoE and ApoE, AT8 and PHF1 containing 18 kDa fragments (by Western blot), expression of ApoE mRNA (by real-time polymerase chain reaction), and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the supernatant (by enzyme-linked immunosorbent assay). Results:Compared with A2C group, the expression of ApoE mRNA and full-length ApoE in neurons was up-regulated ( P<0.05), and no significant change was found in the expression of AT8 and PHF1 and concentrations of TNF-α and IL-6 in the supernatant in A2S group ( P>0.05). Compared with A3C group, the expression of ApoE mRNA, full-length ApoE, and ApoE, AT8 and PHF1 containing 18 kDa fragments was up-regulated, and the concentrations of TNF-α and IL-6 in the supernatant were increased in A3S group ( P<0.05). Conclusion:Sevoflurane may promote phosphorylation of Tau proteins and increase inflammatory responses through up-regulating the expression of ApoE containing 18 kDa fragments, thus leading to neuronal damage.

OBJECTIVE: To observe the analgesic effect of auricular point sticking therapy during the perioperative stage in the patients with partial lung resection. METHODS: A total of 92 patients with partial lung resection were randomized into an auricular point group (31 cases, 1 case dropped off), the sham-auricular point group (30 cases) and a medication group (31 cases, 1 case dropped off). The routine medication for analgesia was provided in all of the three groups. In the auricular point group, 1 day before operation, the auricular point sticking therapy was applied at shenmen (TF RESULTS: In 8, 16, 24, 48 h and 72 h after operation, VAS scores in the auricular point group were lower than those in the sham-auricular point group and the medication group separately ( CONCLUSION Auricular point sticking therapy relieves perioperative pain, shortens analgesic time, releases anxious and depressive emotions and reduces postoperative adverse reaction in the patients with partial lung resection. The analgesic mechanism is probably related to the increase of plasma concentration of β-endorphin.
Acupuncture Points ; Acupuncture, Ear ; Humans ; Lung ; Pain ; Pain Management