OBJECTIVE: To explore the clinical features and management of a child with Chitayat syndrome. METHODS: A child presented at the Fengqing People's Hospital on August 8 2019 was selected as the study subject. Clinical data of the child were retrospectively analyzed. Peripheral blood samples were collected from the child and his father and sister. Whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genome Browser, AlphaFold, and PolyPhen-2 were employed for protein structure simulation and amino acid sequence conservation analysis. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Literature was retrieved from databases including CNKI, Wanfang, and PubMed using the keyword "Chitayat syndrome". The clinical characteristics and prognosis of patients with Chitayat syndrome were reviewed and analyzed. This study was approved by the Ethics Committee the Seventh Affiliated Hospital of Sun Yat-sen University (Ethics No.: KY-2024-086-01). RESULTS: The child was born at full term and had special facial features, skeletal abnormalities, recurrent respiratory tract infections and global developmental delay. WES and Sanger sequencing revealed that he has harbored a heterozygous c.266A>G p.(Tyr89Cys) variant of the ERF gene. Protein structure modeling suggested that the mutant protein has increased spatial distance between the side chain group and DNA, which may reduce its binding affinity to DNA. Amino acid sequence analysis indicated that the p.Tyr89 residue is highly conserved across multiple species. The variant was therefore classified as pathogenic (PM1+PM2_Supporting+PM6+PS1+PP3). The patient was diagnosed with "Chitayat syndrome". Nutritional support and rehabilitation training were recommended, though the child had died of severe pneumonia at 13 months old. Literature retrieval has collected 7 relevant articles, which involved 14 cases of Chitayat syndrome confirmed by genetic testing. Together with our case, all patients had facial dysmorphisms and skeletal deformities. Fourteen patients (93.3%) had respiratory distress. Seven of them (46.7%) had recurrent respiratory infections and 7 (46.7%) were confirmed with respiratory tract malacia. Eight (53.3%) patients had neuropsychological retardation, while 8 (53.3%) had growth delay. The main interventions for Chitayat syndrome include respiratory and nutritional support, and rehabilitation training for developmental delays. CONCLUSION Chitayat syndrome is rarely seen and its clinical manifestations may vary. Airway management and early intervention of developmental delay are important for improving the prognosis.
Humans ; Male ; Exome Sequencing ; Female ; Mutation ; Child, Preschool ; Infant ; Developmental Disabilities/genetics*

Objective:To explore the clinical features and management of a child with Chitayat syndrome.Methods:A child presented at the Fengqing People′s Hospital on August 8 2019 was selected as the study subject. Clinical data of the child were retrospectively analyzed. Peripheral blood samples were collected from the child, father and sister. Whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genome Browser, AlphaFold, and PolyPhen-2 were employed for protein structure simulation and amino acid sequence conservation analysis. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Literature was retrieved from databases including CNKI, Wanfang, and PubMed using the keyword "Chitayat syndrome". The clinical characteristics and prognosis of patients with Chitayat syndrome were reviewed and analyzed. This study was approved by the Ethics Committee the Seventh Affiliated Hospital of Sun Yat-sen University (Ethics No.: KY-2024-086-01).Results:The child was born at full term and had special facial features, skeletal abnormalities, recurrent respiratory tract infections and global developmental delay. WES and Sanger sequencing revealed that she has harbored a heterozygous c. 266A>G p. (Tyr89Cys) variant of the ERF gene. Protein structure modeling suggested that the mutant protein has increased spatial distance between the side chain group and DNA, which may reduce its binding affinity to DNA. Amino acid sequence analysis indicated that the p. Tyr89 residue is highly conserved across multiple species. The variant was therefore classified as pathogenic (PM1+ PM2_Supporting+ PM6+ PS1+ PP3). The patient was diagnosed with "Chitayat syndrome". Nutritional support and rehabilitation training were recommended, though the child had died of severe pneumonia at 13 months old. Literature retrieval has collected 7 relevant articles, which involved 14 cases of Chitayat syndrome confirmed by genetic testing. Together with our case, all patients had facial dysmorphisms and skeletal deformities. Fourteen patients (93.3%) had respiratory distress. Seven of them (46.7%) had recurrent respiratory infections and 7 (46.7%) were confirmed with respiratory tract malacia. Eight (53.3%) patients had neuropsychological retardation, while 8 (53.3%) had growth delay. The main interventions for Chitayat syndrome include respiratory and nutritional support, and rehabilitation training for developmental delays. Conclusion:Chitayat syndrome is rarely seen and its clinical manifestations may vary. Airway management and early intervention of developmental delay are important for improving the prognosis.

Objective:To explore the clinical features and management of a child with Chitayat syndrome.Methods:A child presented at the Fengqing People′s Hospital on August 8 2019 was selected as the study subject. Clinical data of the child were retrospectively analyzed. Peripheral blood samples were collected from the child, father and sister. Whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genome Browser, AlphaFold, and PolyPhen-2 were employed for protein structure simulation and amino acid sequence conservation analysis. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Literature was retrieved from databases including CNKI, Wanfang, and PubMed using the keyword "Chitayat syndrome". The clinical characteristics and prognosis of patients with Chitayat syndrome were reviewed and analyzed. This study was approved by the Ethics Committee the Seventh Affiliated Hospital of Sun Yat-sen University (Ethics No.: KY-2024-086-01).Results:The child was born at full term and had special facial features, skeletal abnormalities, recurrent respiratory tract infections and global developmental delay. WES and Sanger sequencing revealed that she has harbored a heterozygous c. 266A>G p. (Tyr89Cys) variant of the ERF gene. Protein structure modeling suggested that the mutant protein has increased spatial distance between the side chain group and DNA, which may reduce its binding affinity to DNA. Amino acid sequence analysis indicated that the p. Tyr89 residue is highly conserved across multiple species. The variant was therefore classified as pathogenic (PM1+ PM2_Supporting+ PM6+ PS1+ PP3). The patient was diagnosed with "Chitayat syndrome". Nutritional support and rehabilitation training were recommended, though the child had died of severe pneumonia at 13 months old. Literature retrieval has collected 7 relevant articles, which involved 14 cases of Chitayat syndrome confirmed by genetic testing. Together with our case, all patients had facial dysmorphisms and skeletal deformities. Fourteen patients (93.3%) had respiratory distress. Seven of them (46.7%) had recurrent respiratory infections and 7 (46.7%) were confirmed with respiratory tract malacia. Eight (53.3%) patients had neuropsychological retardation, while 8 (53.3%) had growth delay. The main interventions for Chitayat syndrome include respiratory and nutritional support, and rehabilitation training for developmental delays. Conclusion:Chitayat syndrome is rarely seen and its clinical manifestations may vary. Airway management and early intervention of developmental delay are important for improving the prognosis.

Objective:To construct a scientific and objective competency index system for clinical research nurse,providing a reference for establishing a systematic and specialized training system.Methods:A preliminary framework and corresponding indicators for the competency of clinical research nurse were developed through literature analysis with the guidance of the iceberg model.The expert meeting method was utilized to determine the framework,and the Delphi method and Analytic Hierarchy Process were employed to screen indicators and calculate weights.Finally,the competency index system for clinical research nurses was established.Results:In this research,9 experts participated in the expert meeting,confirming that this competency framework consists of two dimensions:knowledge skills and self-concept.The knowledge and skills dimension encompasses five roles of clinical research nurses,and based on this,four levels were further divided.In addition,the self-concept dimension is divided into three aspects.A panel of 17 experts was selected to evaluate these indicators through two Delphi rounds.The effective response rates were 100%and 88.2%,respectively.The expert authority coefficients were 0.968 and 0.963,respectively,while the Kendall's coefficient of concordance were 0.244 and 0.403,respectively(P<0.001).In the end,87 indicators for clinical research nurse competency were developed.Conclusion:Under the guidance of the iceberg model,the competency index system for clinical research nurse constructed in this study is scientific and reliable,closely aligned with clinical practice,and possesses specialized characteristics.It can be used to evaluate the competencies of clinical research nurses and provides a basis for conducting relevant training and improving position management.

Antibody-drug conjugate(ADC)is a novel targeted drug composed of monoclonal antibodies,cytotoxic drugs,and their chemical linkers.Among them,ADC drugs targeting trophoblast cell surface antigen 2(Trop-2)are currently one of the research hotspots.Since the first Trop-2 targeted ADC,sacituzumab govitecan(SG),was approved by the FDA in April 2021,multiple Trop-2 targeted ADCs such as Dato-DXd,SKB264,ESG-401 and SHR-A1921 are currently undergoing clinical trials.The Trop-2 targeted ADCs have achieved clinical efficacy,but the related adverse events were reported.Furthermore,both the monoclonal antibody and cytotoxic drug of ADC may lead to adverse events.Therefore,it is particularly important to improve drug-related adverse events through pertinent nursing assessments and interventions during clinical trials.The official websites of the National Institutes of Health,the Drug Evaluation Center of the National Medical Products Administration,the Food and Drug Administration,China National Knowledge Infrastructure,Wanfang Data,PubMed,Web of Science and other related databases were searched to review the application of ADC drugs targeting Trop-2 in advanced solid malignant tumors,summarizing the common adverse events and the corresponding nursing interventions of such drugs,and providing references for clinical trials.

Objective:To construct a scientific and objective competency index system for clinical research nurse,providing a reference for establishing a systematic and specialized training system.Methods:A preliminary framework and corresponding indicators for the competency of clinical research nurse were developed through literature analysis with the guidance of the iceberg model.The expert meeting method was utilized to determine the framework,and the Delphi method and Analytic Hierarchy Process were employed to screen indicators and calculate weights.Finally,the competency index system for clinical research nurses was established.Results:In this research,9 experts participated in the expert meeting,confirming that this competency framework consists of two dimensions:knowledge skills and self-concept.The knowledge and skills dimension encompasses five roles of clinical research nurses,and based on this,four levels were further divided.In addition,the self-concept dimension is divided into three aspects.A panel of 17 experts was selected to evaluate these indicators through two Delphi rounds.The effective response rates were 100%and 88.2%,respectively.The expert authority coefficients were 0.968 and 0.963,respectively,while the Kendall's coefficient of concordance were 0.244 and 0.403,respectively(P<0.001).In the end,87 indicators for clinical research nurse competency were developed.Conclusion:Under the guidance of the iceberg model,the competency index system for clinical research nurse constructed in this study is scientific and reliable,closely aligned with clinical practice,and possesses specialized characteristics.It can be used to evaluate the competencies of clinical research nurses and provides a basis for conducting relevant training and improving position management.

Antibody-drug conjugate(ADC)is a novel targeted drug composed of monoclonal antibodies,cytotoxic drugs,and their chemical linkers.Among them,ADC drugs targeting trophoblast cell surface antigen 2(Trop-2)are currently one of the research hotspots.Since the first Trop-2 targeted ADC,sacituzumab govitecan(SG),was approved by the FDA in April 2021,multiple Trop-2 targeted ADCs such as Dato-DXd,SKB264,ESG-401 and SHR-A1921 are currently undergoing clinical trials.The Trop-2 targeted ADCs have achieved clinical efficacy,but the related adverse events were reported.Furthermore,both the monoclonal antibody and cytotoxic drug of ADC may lead to adverse events.Therefore,it is particularly important to improve drug-related adverse events through pertinent nursing assessments and interventions during clinical trials.The official websites of the National Institutes of Health,the Drug Evaluation Center of the National Medical Products Administration,the Food and Drug Administration,China National Knowledge Infrastructure,Wanfang Data,PubMed,Web of Science and other related databases were searched to review the application of ADC drugs targeting Trop-2 in advanced solid malignant tumors,summarizing the common adverse events and the corresponding nursing interventions of such drugs,and providing references for clinical trials.

Objective:To investigate the effect of tumor-associated macrophage(TAM) on proliferation of renal carcinoma cells and its related mechanism.Methods:The model of TAM was established by stimulating human monocytic leukemia cell line THP-1 with phorbol myristate acetate (PMA), bacterial endotoxin (LPS) and interferon-γ (IFN- γ). Then the TAM model was co-cultured with carcinoma cell lines ACHN and 786-O in vitro .The cytokines IL-6, TNF-α and IL-1β in TAM supernatant were detected by enzyme-linked immunosorbent assay (ELISA). MTT method was used to detect the proliferation of ACHN and 786-O cells treated with supernatant of TAM or TAM/Tocilizumab. Western blot was used to detect lactate dehydrogenase A (LDHA) expression of both renal cancer cells co-cultured with TAM or TAM/Tocilizumab. The ACHN and 786-O cells with LDHA-overexpression and LDHA-knockdown were cultured in TAM supernatant in vitro. The cell proliferation was detected by MTT and the relative proliferation rate was calculated.Results:THP-1 cells was differentiated into TAM through the treatment of 80 ng/ml PMA combined with 20 ng/ml LPS and 20 ng/ml IFN- γ.The expression rate of CD68, a cell surface marker on TAM, was (36.2 ±4.5)%. When TAM was co-cultured with ACHN cells, the results of ELISA showed that the secretion of IL-6 in the supernatant was significantly elevated compared with that in the supernatant when ACHN cells cultured alone [(138.0 ±12.4) pg/ml and (19.7±4.9) pg/ml], and the secretion of TNF- α [(122.5 ±14.2) pg/ml and (12.6 ±2.3) pg/ml] and IL-1 β [(89.2 ±6.4) pg/ml and (69.2 ±3.5) pg/ml] were also significantly increased. The secretion of IL-6 [(119.2 ±14.8) pg/ml and (17.1 ±3.3) pg/ml], TNF- α [(122.6 ±14.4) pg/ml and (45.7 ±7.2) pg/ml] and IL-1 β [(95.1 ±11.8) pg/ml and (88.2 ±12.7) pg/ml] in the supernatant were also significantly elevated when 786-O cells co-cultured with TAM compared with 786-O cells cultured alone. After treated with the supernatant of TAM for 72 hours, the relative proliferation rates of ACHN and 786-O cells [(128.6 ±21.4)% and (124.2 ±19.7)%] were significantly higher than that of the control group (100.0%). At the same time, the expression of LDHA in ACHN and 786-O cells increased significantly. After 72 hours of treatment with the supernatant of TAM combined with tocilizumab, the relative proliferation rates of ACHN and 786-O cells [(76.5±13.7)% and (74.8±12.5)%] were significantly lower than that of the control group(100.0%), and the expression of LDHA was also significantly decreased at the same time. The relative proliferation rates of ACHN and 786-O cells in LDHA overexpression group [(121.5 ±17.2)% and (122.7±21.6)%]were significantly higher than that in blank-vector-transfection group[(93.3±10.7)% and (89.8±11.2)%], while the relative proliferation rates in LDHA-knockdown group [(61.4±11.2)% and (58.0 ±10.6)% ]were significantly lower than that in blank-vector-transfection group.Conclusions:By secreting IL-6, TAM can up-regulate the expression of LDHA and promote the proliferation of renal cancer cells.

Objective: To identify the time window during which the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a key role in telogen-to-anagen transition of hair follicles, and to explore whether the pathway specifically promotes the proliferation of hair follicle stem cells (HFSCs) . Methods: Totally, 36 newborn ICR mice were randomly and equally divided into 3 groups: RAPA-P19 group intraperitoneally injected with 5 mg·kg^-1·d^-1 sirolimus on days 19-24 after birth, RAPA-P21 group intraperitoneally injected with 5 mg·kg^-1·d^-1 sirolimus on days 21-24 after birth, and control group intraperitoneally injected with the same volume of solvent on days 19-24 after birth. Four mice were sacrificed in each group on days 22, 23 and 24 separately. Skin tissues were resected from the back, and hematoxylin-eosin staining of the skin tissues were performed followed by observation of hair follicle morphology to evaluate whether murine hair follicles progressed into the anagen phase on day 24. Immunofluorescence costaining was conducted to determine the expression and localization of mTORC1 downstream molecular marker pS6 and cell proliferation marker Ki67 on days 22 and 23. Results: On day 24, hematoxylin-eosin staining showed anagen hair follicles in the control group and RAPA-P21 group, but telogen hair follicles in the RAPA-P19 group. On days 22 and 23, immunofluorescence costaining revealed positive staining for both pS6 and Ki67 in HFSCs in the control group, negative staining for both pS6 and Ki67 in the RAPA-P19 group, negative staining for pS6 and positive staining for Ki67 in the RAPA-P21 group. On day 23, epidermal cells and sebaceous gland cells in the upper hair follicle bulge were stained positively for Ki67 in all the 3 groups. Conclusion mTORC1 signaling specifically promotes the proliferation of HFSCs during telogen-to-anagen transition, but not affects proliferation of other cells in hair follicles.

To detemine the expression pattern of mTOR complex subunits Raptor and Rictor in the hair follicles of mice at different hair follicle stages, and to explore its significance. 
 Methods: Immunostaining of Ki-67, a proliferative marker, was used to determine the precise hair follicle stages of mouse dorsal skin at different postnatal time points. Real-time PCR was used to detect the mRNA expression of Raptor and Rictor in mouse dorsal skin at 43 days after birth (P43, early telogen), 56 days after birth (P56, mid-telogen), 69 days after birth (P69, late telogen) and 74 days after birth (P74, early anagen). The expression intensity and localization of Raptor and Rictor at different stages of hair cycle were tested by co-immumostaining.
 Results: Ki-67 immunostaining showed that the time points (P43, P56, P69, P74) and hair follicle stages (early telogen, mid-telogen, late telogen, early anagen) of the dorsal skin were consistent with each other. The results of real-time PCR and immunostaining were consistent, showing that the expression of Raptor and Rictor did not changed in the early-, mid-, late telogen, and early anagen. However, Raptor was specifically expressed in the bulge where hair follicle stem cells (HFSCs) are residing in, and Rictor was mainly detected in inner root sheath (IRS) cells. 
 Conclusion: The expression of Raptor and Rictor does not altered in the hair follicles at different hair follicle stages, but Raptor and Rictor are specifically expressed in the HFSCs and IRS cells, respectively, indicating that Raptor might be a molecular marker for HFSCs, and Rictor might be involved in the maintenance of IRS and formation of hair shaft.
Animals ; Hair ; Hair Follicle ; Mice ; Rapamycin-Insensitive Companion of mTOR Protein ; Raptors ; Skin ; TOR Serine-Threonine Kinases