Objective:To construct an early rehabilitation exercise program for patients with agoraphobia after total knee arthroplasty (TKA) to provide guidance for orthopedic rehabilitation nursing practice.Methods:The first draft of an early rehabilitation exercise program for patients with agoraphobia after TKA was developed through literature search, semi-structured interviews, and group discussions. From November to December 2023, 20 experts from nine provinces and centrally administered municipalities were selected for two rounds of expert consultation using the Delphi method to form the final draft of the early rehabilitation exercise program for patients with agoraphobia after TKA.Results:In two rounds of consultation, the questionnaire recovery rates were 91.30% (21/23) and 95.24% (20/21), with authority coefficients of 0.92 and 0.96, and Kendall's coordination coefficients of 0.28 and 0.34, respectively ( P<0.05). After the second round of consultation, the mean importance assignment scores for all levels of indicators ranged from 3.90 to 5.00, with coefficients of variation ranging from 0 to 0.20. The finalized early rehabilitation exercise program for patients with agoraphobia after TKA contained two parts, including the preface and the main text, and the main text consisted of five first-level items, 21 second-level items, and 35 third-level items. Conclusions:The content of the early rehabilitation exercise program for patients with agoraphobia after TKA is scientific, reasonable, comprehensive, practical and targeted, which can provide a basis for clinical medical and nursing personnel to guide the early rehabilitation exercise for patients with agoraphobia after TKA.

OBJECTIVE: To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. METHODS: A child diagnosed with 3MS type 1 at the Children's Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020). RESULTS: The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. WES revealed compound heterozygous variants in the CUL7 gene: c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child's father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c.2686G>T (p.E896) was classified as a pathogenic (PVS1+PM2_Supporting+PM3), and c.1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+PM2_Supporting). Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). CONCLUSION The compound heterozygous variants c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.
Humans ; Cullin Proteins/genetics* ; Female ; Child ; Limb Deformities, Congenital/genetics* ; Exome Sequencing ; Mutation ; Child, Preschool ; Dwarfism ; Muscle Hypotonia ; Spine/abnormalities*

Objective:To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. Methods:A child diagnosed with 3MS type 1 at the Children′s Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020).Results:①The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. ②WES revealed compound heterozygous variants in the CUL7 gene: c. 2686G>T (p.E896*) and c. 1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child′s father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c. 2686G>T (p.E896) was classified as a pathogenic (PVS1+ PM2_Supporting+ PM3), and c. 1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+ PM2_Supporting). ③ Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). Conclusion:The compound heterozygous variants c.2686G>T (p.E896*) and c. 1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.

Objective:To investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.

Objective:To construct an early rehabilitation exercise program for patients with agoraphobia after total knee arthroplasty (TKA) to provide guidance for orthopedic rehabilitation nursing practice.Methods:The first draft of an early rehabilitation exercise program for patients with agoraphobia after TKA was developed through literature search, semi-structured interviews, and group discussions. From November to December 2023, 20 experts from nine provinces and centrally administered municipalities were selected for two rounds of expert consultation using the Delphi method to form the final draft of the early rehabilitation exercise program for patients with agoraphobia after TKA.Results:In two rounds of consultation, the questionnaire recovery rates were 91.30% (21/23) and 95.24% (20/21), with authority coefficients of 0.92 and 0.96, and Kendall's coordination coefficients of 0.28 and 0.34, respectively ( P<0.05). After the second round of consultation, the mean importance assignment scores for all levels of indicators ranged from 3.90 to 5.00, with coefficients of variation ranging from 0 to 0.20. The finalized early rehabilitation exercise program for patients with agoraphobia after TKA contained two parts, including the preface and the main text, and the main text consisted of five first-level items, 21 second-level items, and 35 third-level items. Conclusions:The content of the early rehabilitation exercise program for patients with agoraphobia after TKA is scientific, reasonable, comprehensive, practical and targeted, which can provide a basis for clinical medical and nursing personnel to guide the early rehabilitation exercise for patients with agoraphobia after TKA.

Objective:To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. Methods:A child diagnosed with 3MS type 1 at the Children′s Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020).Results:①The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. ②WES revealed compound heterozygous variants in the CUL7 gene: c. 2686G>T (p.E896*) and c. 1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child′s father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c. 2686G>T (p.E896) was classified as a pathogenic (PVS1+ PM2_Supporting+ PM3), and c. 1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+ PM2_Supporting). ③ Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). Conclusion:The compound heterozygous variants c.2686G>T (p.E896*) and c. 1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.

Objective:To investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.

Objective To explore the construction and practice of an intelligent prevention and treatment system for venous thromboembolism (VTE) in grassroots hospitals. Methods Based on relevant guidelines and expert consensuses on VTE prevention and treatment, domestic and foreign literature was reviewed. A research and development team composed of clinical experts in VTE prevention and treatment, medical and nursing quality management experts, and information engineers conducted investigations and research in surrounding grassroots hospitals. Through evidence-based research and surveys, the team identified relevant business needs, user needs, and functional requirements of grassroots hospitals, and finally formulated a detailed design plan. The main program of system was written in Java. The interface obtained data from the hospital's data platform through Webservice and view interfaces. To prevent issues of repeated data extraction when multiple applications perform time tasks to assess the same patient during later server usage and expansion, the XXL-JOB distributed task scheduling platform was adopted to handle VTE assessments by medical staff. Results After the clinical application of the intelligent VTE prevention and treatment system, the bleeding risk assessment rate increased from 26.20% at the initial system launch in January 2023 to 83.04% by the end of 2023. In January 2023, the implementation rates of mechanical prevention, pharmacological prevention, and combined prevention for medium-to-high-risk VTE patients were 21.39%, 16.39%, and 5.26%, respectively, which increased to 51.75%, 25.50%, and 25.65% in December 2023. Conclusion The VTE prevention and treatment software system developed by grassroots hospitals can improve development efficiency, enhance the clinical practicality of the system, reduce the workload of medical staff, promote standardization and normalization in VTE prevention and treatment, strengthen closed-loop management of medical quality for VTE as a single disease, and effectively improve the prevention and treatment capabilities and levels of VTE within hospitals.

Objective:To explore the expression levels of adrenomedullin (ADM) in follicular fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study, the data on infertile couples who received an antagonistic regimen of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) were collected. PCOS patients were selected as the PCOS group, and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group. The general clinical data of two groups of patients were analyzed, and the expression of ADM, interleukin 1β (IL-1β), IL-18, transforming growth factor β (TGF-β) in the follicular fluid were compared between the two groups of patients. And taking the concentration of ADM in follicular fluid as the main research indicator, correlation and multiple linear regression analysis were conducted with other indicators. Simultaneously the ADM mRNA expression, cell cycle and cell apoptosis of granulosa cells were compared between the two groups. Results:This study included 20 cases in the PCOS group and 20 cases in control group. Compared with control group, the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower (both P<0.001), while its testosterone, the ratio of luteinizing hormone and follicle-stimulating hormone, antral follicle count (AFC), number of retrieved eggs, ovarian sensitivity index, as well as IL-1β, IL-18 and TGF-β in follicular fluid were higher and negatively correlated with ADM ( r=-0.37, P=0.019; r=-0.32, P=0.047; r=-0.50, P<0.001; r=-0.38, P=0.017; r=-0.38, P=0.016; r=-0.44, P=0.005; r=-0.37, P=0.018; r=-0.54, P<0.001). Multiple linear regression showed that AFC, gonadotropin initiation dose, IL-1β and TGF-β were the independent related factors that affect local ADM levels ( r=-0.37, P=0.008; r=-0.27, P=0.035; r=-0.28, P=0.028; r=-0.45, P<0.001). There was no statistically significant difference in the cell cycle of granulocytes between the two groups ( P>0.05), but the apoptosis rate (AR) of granulocytes was higher in the PCOS group than in control group (median AR in the PCOS group was 46.07%, median AR in control group was 28.57%, n=10, P=0.036). Conclusion:The decreased expression of ADM in follicles of PCOS patients is related to ovarian endocrine disorders, multiple vesicles, high ovarian responsiveness and local inflammatory status.

Objective:To explore the expression levels of adrenomedullin (ADM) in follicular fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study, the data on infertile couples who received an antagonistic regimen of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) were collected. PCOS patients were selected as the PCOS group, and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group. The general clinical data of two groups of patients were analyzed, and the expression of ADM, interleukin 1β (IL-1β), IL-18, transforming growth factor β (TGF-β) in the follicular fluid were compared between the two groups of patients. And taking the concentration of ADM in follicular fluid as the main research indicator, correlation and multiple linear regression analysis were conducted with other indicators. Simultaneously the ADM mRNA expression, cell cycle and cell apoptosis of granulosa cells were compared between the two groups. Results:This study included 20 cases in the PCOS group and 20 cases in control group. Compared with control group, the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower (both P<0.001), while its testosterone, the ratio of luteinizing hormone and follicle-stimulating hormone, antral follicle count (AFC), number of retrieved eggs, ovarian sensitivity index, as well as IL-1β, IL-18 and TGF-β in follicular fluid were higher and negatively correlated with ADM ( r=-0.37, P=0.019; r=-0.32, P=0.047; r=-0.50, P<0.001; r=-0.38, P=0.017; r=-0.38, P=0.016; r=-0.44, P=0.005; r=-0.37, P=0.018; r=-0.54, P<0.001). Multiple linear regression showed that AFC, gonadotropin initiation dose, IL-1β and TGF-β were the independent related factors that affect local ADM levels ( r=-0.37, P=0.008; r=-0.27, P=0.035; r=-0.28, P=0.028; r=-0.45, P<0.001). There was no statistically significant difference in the cell cycle of granulocytes between the two groups ( P>0.05), but the apoptosis rate (AR) of granulocytes was higher in the PCOS group than in control group (median AR in the PCOS group was 46.07%, median AR in control group was 28.57%, n=10, P=0.036). Conclusion:The decreased expression of ADM in follicles of PCOS patients is related to ovarian endocrine disorders, multiple vesicles, high ovarian responsiveness and local inflammatory status.