Objective: To evaluate the suitability of the existing hemolysis rate standards for locally processed red blood cell components by retrospectively analyzing 5-year hemolysis rate data at the end of storage. Methods: A total of 720 blood samples of three types of red blood cell components from our blood station from January 2019 to December 2023 were collected. Parameters included hemoglobin concentration (Hb), hematocrit (Hct), and free hemoglobin concentration (fHb). Hemolysis rate were taken as the control standard of 0.8% in accordance with the national standard. The hemolysis rates were compared against the national standard threshold of 0.8% (GB18469-2012), and annual trends of the detection parameters were observed. Results: The hemolysis rates (x-+s,%) of leukocyte-depleted whole blood at the end of storage were (0.038±0.023 8) in 2019, (0.049±0.039 5) in 2020, (0.043±0.040 7) in 2021, (0.049±0.030 7) in 2022, and (0.058±0.054 8) in 2023, respectively; The hemolysis rates (x-+s" />,%) of leukocyte-depleted suspended red blood cells at the end of storage were (0.093±0.050 2) in 2019, (0.086±0.049 5) in 2020, (0.123±0.072 3) in 2021, (0.122±0.052 1) in 2022, and (0.106±0.058 6) in 2023, respectively; The hemolysis rates (x-+s,%) of washed red blood cells at the end of storage were (0.127±0.038 2) in 2019, (0.150±0.066 5) in 2020, (0.121±0.052 2) in 2021, (0.124±0.038 9) in 2022, and (0.128±0.044 3) in 2023, respectively. Conclusion: Hemolysis rates at the end of blood storage of three red blood cell components were significantly lower than the limits specified in Quality Requirements for Whole Blood and Components (GB18469-2012), as well as standards from the EU, AABB and the United States. The results demonstrate excellent product quality control. A regional internal control standard of <0.2% is proposed for hemolysis rates at the end of storage.

OBJECTIVE: To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses. METHODS: Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children's Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201). RESULTS: A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c.735T>C, ALPL: c.1324C>T, NEK9: c.1973G>A, MAGEL2: c.2024_2025del, LMBR1: c.423+4914A>C, NEB: c.21273_21276del, COL1A1: c.2651G>C and c.2758G>C, ASPM: c.2473delinsGA, TBX5: c.704G>A, DYNC2H1: c.10893del, and DYNC2I2: c.1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. CONCLUSION Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.
Humans ; Exome Sequencing/methods* ; Female ; Pregnancy ; DNA Copy Number Variations/genetics* ; Genetic Testing/methods* ; Prenatal Diagnosis/methods* ; Adult ; Male ; Fetus ; Bone Diseases, Developmental/diagnosis* ; Ultrasonography, Prenatal

Objective To investigate how vismodegib(Vis)influences the pathogenesis of basal cell carcinoma(BCC)via a chromatin remodeling factor,bromodomain containing protein 9(BRD9),and to analyze the expression profile of BRD9 in BCC and its relationship with the immune checkpoint,programmed cell death-1 ligand 1(PD-L1)and the Hedgehog(Hh)signaling pathway.Methods ① A UVB-induced BCC model was established in SKH-1 hairless background Ptch1+/-;LacZ reporter mice.Then the mice were treated with Vis,and those without treatment served as control.X-gal staining,immunohistochemistry(IHC)staining,immunofluorescence(IF)assay,and Western blotting were used to assess the expression and localization of BRD9 and PD-L1 in tumor tissues and to evaluate immune-cell infiltration.② In vitro,mouse BCC cell line ASZ001(ASZ cells)were treated with Vis or a BRD9 degrader(dBRD9),and BRD9-overexpressing cells were generated.Cell viability and the protein and mRNA levels of BRD9,PD-L1,Gli1,and cyclin D1(Ccnd1)were measured.ChIP-qPCR was performed to examine BRD9 and H3K27ac enrichment at the PD-L1 promoter,including the promoter-proximal site(P1)and an upstream active segment(P2).Results ① At the tissue level,BRD9 was highly expressed in BCC,and co-localization of BRD9 and PD-L1 was observed within tumor regions,with evident immune-cell infiltration.Vis markedly suppressed UVB-induced BCC formation,reduced the probability of large-volume tumors(by probability-density analysis),decreased the X-gal-positive lesion area(P<0.000 1),down-regulated BRD9(P=0.024 9),and attenuated immune-cell infiltration.② At the cellular level,Vis treatment reduced cell viability and down-regulated BRD9,Gli1,and Ccnd1 in ASZ cells(P<0.000 1).dBRD9 inhibited ASZ cell viability in a dose-dependent manner and decreased PD-L1,Gli1,and Ccnd1(P<0.000 1),whereas its overexpression increased the expression of these molecules(P<0.000 1).In ASZ cells,BRD9 and H3K27ac were enriched at the PD-L1 promoter P1/P2 regions.Treatment with dBRD9 or Vis reduced BRD9 and H3K27ac enrichment at P1/P2 regions(P<0.000 1).Conclusion In BCC,BRD9 maintains chromatin activation at the proximal PD-L1 promoter and modulates Hh/Gli1 signaling,thereby promoting immune evasion.Vis remodels the tumor immune microenvironment by inhibiting the Hh-BRD9-PD-L1 axis.

Objective:To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses.Methods:Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children′s Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201).Results:A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c. 735T>C, ALPL: c. 1324C>T, NEK9: c. 1973G>A, MAGEL2: c. 2024_2025del, LMBR1: c. 423+ 4914A>C, NEB: c. 21273_21276del, COL1A1: c. 2651G>C and c. 2758G>C, ASPM: c. 2473delinsGA, TBX5: c. 704G>A, DYNC2H1: c. 10893del, and DYNC2I2: c. 1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. Conclusion:Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain in patients undergoing modified radical mastectomy for breast cancer. METHODS: A total of 140 female patients scheduled for unilateral modified radical mastectomy for breast cancer undergoing general anesthesia were randomized into a TEAS group (70 cases) and a sham TEAS group (70 cases, 2 cases dropped out). Patients in both groups received TEAS or sham TEAS at bilateral Neiguan (PC6), Zusanli (ST36), and Danzhong (CV17), respectively, from 30 min before anesthesia induction until the end of surgery, and on 1st, 2nd, and 3rd days after surgery for 30 min a time, once a day. On 1st, 2nd, and 3rd days after surgery, the pain visual analogue scale (VAS) score was observed; on 3, 6, 12 months after surgery, the incidence rate of chronic pain was observed; before surgery, and on 1st, 3rd, and 7th days after surgery, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were detected; the number of analgesia pump press, rescue analgesia, and the occurrence of adverse reaction after surgery were recorded in the two groups. RESULTS: In the TEAS group, the VAS scores on 1st and 2nd days after surgery, and the incidence rates of chronic pain on 3 and 6 months after surgery were lower than those in the sham TEAS group (P<0.05). On 1st, 3rd, and 7th days after surgery, the serum levels of TNF-α, IL-6, and IL-10 were increased compared with those before surgery in both groups (P<0.05, P<0.01); the above indexes in the TEAS group were lower than those in the sham TEAS group (P<0.05). The number of analgesia pump press and the incidence rate of rescue analgesia after surgery in the TEAS group were lower than those in the sham TEAS group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions after surgery between the two groups (P>0.05). CONCLUSION TEAS can effectively improve both the postoperative acute pain and chronic pain in patients undergoing modified radical mastectomy for breast cancer, the mechanism may relate to inhibiting the inflammatory reaction.
Humans ; Female ; Acupuncture Points ; Pain, Postoperative/blood* ; Middle Aged ; Breast Neoplasms/surgery* ; Adult ; Transcutaneous Electric Nerve Stimulation ; Mastectomy, Modified Radical/adverse effects* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-10/blood* ; Aged

Objective To assess the nutritional status of patients undergoing preventive ileostomy and identify the factors that influence the status,thereby providing guidance for medical staff to formulate nutritional intervention strategies.Methods Convenient sampling was used to select 239 patients undergoing preventive ileostomy who were attending follow-up visits or hospitalized while awaiting stoma closure at 4 tertiary hospitals in Guangzhou from November 2023 to July 2024.Data was collected by a general information questionnaire and the Patient-Generated Subjective Global Assessment tool.Factors influencing nutritional status were analyzed by multivariable ordinal Logistic regression.Results Of the 239 patients,227 provided valid responses.The nutritional status was categorized as follows:64 patients(28.19％)had good nutrition or were at risk of malnutrition;104(45.81％)exhibited moderate malnutrition;59(25.99％)had severe malnutrition.Multivariable ordinal Logistic regression analysis revealed that preoperative cumulative chemotherapy cycles,postoperative duration,age,current dietaiy type,use of oral nutritional supplements(ONS),enterostomy-related complications,and stoma self-care ability were significant predictors of nutritional status(P＜0.05).Conclusion Patients undergoing preventive ileostomy are at a high risk of moderate to severe malnutrition and ONS provided to patients did not result in a meaningful improvement in their nutritional health.Specifically,those patients with a higher number of cumulative preoperative chemotherapy cycles,shorter postoperative recovery time,aged ≥ 65 years,liquid diet or semi-liquid diet,experiencing enterostomy-related complications,or poor stoma self-care ability,are particularly vulnerable to malnutrition.These findings underscore the need for medical staff to formulate intervention strategies based on these factors to improve nutritional status of patients undergoing preventive ileostomy.

Objective To analyze relevant literature on the essence of traditional Chinese medicine syndromes using bibliometric methods;To understand the current research status and hotspots in this field;To provide references for relevant research.Methods Research literature about the essence of TCM syndromes was retrieved from CNKI,VIP,Wanfang Data and CBM from 1st Jan.1979 to 30th June 2024.CiteSpace 6.2 software was used to conduct visualization analysis on authors,institutions,keywords,etc.Results A total of 695 articles were included,with an overall upward trend in publication volume followed by stabilization.The authors who published more articles included Luo Ren(13 articles),Zhao Xiaoshan(13 articles),Li Zegeng(12 articles),etc.The institutions with more publications included Shandong University of Traditional Chinese Medicine(35 articles),Beijing University of Chinese Medicine(33 articles),Chengdu University of Traditional Chinese Medicine(26 articles),etc.Institutions were clustered regionally,and cooperation was mostly between TCM universities and their affiliated hospitals,with less cross regional communication.High frequency keywords included kidney yang deficiency syndrome,metabolomics,animal models,TCM syndrome types,coronary heart disease,lung qi deficiency syndrome,spleen qi deficiency syndrome,liver depression and spleen deficiency syndrome,etc;Keyword clustering covered aspects such as biomolecules and metabolism,TCM syndromes,pathology,disease models,and animal research.Conclusion Research in the field of the essence of TCM syndromes is gradually receiving more attention.Exploring the essence of TCM syndromes at the molecular level through techniques such as genomics,transcriptomics,metabolomics and proteomics is a research hotspot and trend in this field.

Objective To investigate whether ginsenoside Rg3 can ameliorate glomerular endothelial injury in diabetic nephropathy(DN)mice through Ras homologous gene family member A(Rho A)/Rho-associated coiled-coil forming protein kinase,(ROCK1)/NLR family pyrin domain protein 3(NLRP3)pathway.Methods Forty mice were randomly divided into 4 groups:control group,DN group,ginsenoside(ginsenoside Rg3)group and RhoA/ROCK pathway inhibition(FD)group,with 10 mice in each group.Fasting blood glucose(FBG)was measured by glucose meter.The levels of urinary protein,urea nitrogen(BUN)and serum creatinine(SCr)were detected by ELISA.PAS staining was used to detect glomerular morphology and structure and to evaluate glomerular injury index(GDI).The expression of platelet-endothelial cell adhesion molecule(PECAM-1 or CD31),von Willefibrilia factor(vWF),RhoA,ROCK and NLRP3 protein related to pyrodeath were detected by immunofluorescence staining.Western blotting detected the expression of intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),the inflammatory factor interleukin-1β(IL-1β)and IL-18 protein in the glomerulus.Results Compared with the control group,the levels of FPG,urinary protein,BUN and SCr in DN group were increased,and the differences were statistically significant(t=17.59～43.81,all P<0.05).The glomerular structure was significantly damaged and GDI was increased(t=20.73,P<0.05).The expressions of CD31,RhoA,ROCK and NLRP3 in glomeruli were increased,while the expression of vWF was decreased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues were increased,and the differences were statistically significant(t=27.95～40.10,all P<0.05).Compared with the DN group,the levels of FPG,urinary protein,BUN and SCr in ginsenoside group were decreased,and the differences were statistically significant(t=14.87～20.33,all P<0.05).The damage of glomerular structure was improved and GDI was decreased(t=19.80,P<0.05),the expression of CD31,RhoA,ROCK and NLRP3 in glomerular was decreased,and the expression of vWF was increased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues of FD group were decreased,and the differences were statistically significant(t=12.62～39.68,all P<0.05).Conclusion Ginsenosides Rg3 can improve the level of glomerular endothelial injury and pyroptosis in DN mice by down-regulating RhoA/ROCK/NLRP3 pathway.

Objective To investigate whether ginsenoside Rg3 can ameliorate glomerular endothelial injury in diabetic nephropathy(DN)mice through Ras homologous gene family member A(Rho A)/Rho-associated coiled-coil forming protein kinase,(ROCK1)/NLR family pyrin domain protein 3(NLRP3)pathway.Methods Forty mice were randomly divided into 4 groups:control group,DN group,ginsenoside(ginsenoside Rg3)group and RhoA/ROCK pathway inhibition(FD)group,with 10 mice in each group.Fasting blood glucose(FBG)was measured by glucose meter.The levels of urinary protein,urea nitrogen(BUN)and serum creatinine(SCr)were detected by ELISA.PAS staining was used to detect glomerular morphology and structure and to evaluate glomerular injury index(GDI).The expression of platelet-endothelial cell adhesion molecule(PECAM-1 or CD31),von Willefibrilia factor(vWF),RhoA,ROCK and NLRP3 protein related to pyrodeath were detected by immunofluorescence staining.Western blotting detected the expression of intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),the inflammatory factor interleukin-1β(IL-1β)and IL-18 protein in the glomerulus.Results Compared with the control group,the levels of FPG,urinary protein,BUN and SCr in DN group were increased,and the differences were statistically significant(t=17.59～43.81,all P<0.05).The glomerular structure was significantly damaged and GDI was increased(t=20.73,P<0.05).The expressions of CD31,RhoA,ROCK and NLRP3 in glomeruli were increased,while the expression of vWF was decreased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues were increased,and the differences were statistically significant(t=27.95～40.10,all P<0.05).Compared with the DN group,the levels of FPG,urinary protein,BUN and SCr in ginsenoside group were decreased,and the differences were statistically significant(t=14.87～20.33,all P<0.05).The damage of glomerular structure was improved and GDI was decreased(t=19.80,P<0.05),the expression of CD31,RhoA,ROCK and NLRP3 in glomerular was decreased,and the expression of vWF was increased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues of FD group were decreased,and the differences were statistically significant(t=12.62～39.68,all P<0.05).Conclusion Ginsenosides Rg3 can improve the level of glomerular endothelial injury and pyroptosis in DN mice by down-regulating RhoA/ROCK/NLRP3 pathway.

Objective To assess the nutritional status of patients undergoing preventive ileostomy and identify the factors that influence the status,thereby providing guidance for medical staff to formulate nutritional intervention strategies.Methods Convenient sampling was used to select 239 patients undergoing preventive ileostomy who were attending follow-up visits or hospitalized while awaiting stoma closure at 4 tertiary hospitals in Guangzhou from November 2023 to July 2024.Data was collected by a general information questionnaire and the Patient-Generated Subjective Global Assessment tool.Factors influencing nutritional status were analyzed by multivariable ordinal Logistic regression.Results Of the 239 patients,227 provided valid responses.The nutritional status was categorized as follows:64 patients(28.19％)had good nutrition or were at risk of malnutrition;104(45.81％)exhibited moderate malnutrition;59(25.99％)had severe malnutrition.Multivariable ordinal Logistic regression analysis revealed that preoperative cumulative chemotherapy cycles,postoperative duration,age,current dietaiy type,use of oral nutritional supplements(ONS),enterostomy-related complications,and stoma self-care ability were significant predictors of nutritional status(P＜0.05).Conclusion Patients undergoing preventive ileostomy are at a high risk of moderate to severe malnutrition and ONS provided to patients did not result in a meaningful improvement in their nutritional health.Specifically,those patients with a higher number of cumulative preoperative chemotherapy cycles,shorter postoperative recovery time,aged ≥ 65 years,liquid diet or semi-liquid diet,experiencing enterostomy-related complications,or poor stoma self-care ability,are particularly vulnerable to malnutrition.These findings underscore the need for medical staff to formulate intervention strategies based on these factors to improve nutritional status of patients undergoing preventive ileostomy.