OBJECTIVE: To explore the molecular mechanism of a case with RhD-- phenotype. METHODS: A proband with RhD-- phenotype who attended the clinic of the First Affiliated Hospital of Zhengzhou University on January 29, 2024 was selected as the study subject. Peripheral blood samples were collected from the proband (8 mL) and her close relatives (father, mother and brother; 3 mL each) for Rh phenotyping and irregular antibodies testing with gel card and test tube methods. Direct agglutination reaction and absorption-elution test were used to detect the c antigen on the red blood cells of the proband. PCR-sequence specific primers (PCR-SSP) typing and gene sequencing were used to determine the RHCE gene of the proband and her relatives. The origin of the proband's variant was traced by pedigree analysis. Three-dimensional structural models of the wild-type RhCE*cE protein and the RhD-- phenotype protein were constructed to predict the alterations of the RhD-- phenotype protein caused by the variant. The procedures of this study were approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No.: 2023-KY-0870-003). RESULTS: The red blood cells of the proband did not agglutinate with anti-C, anti-c, anti-E, and anti-e. The result of the serum irregular antibody test was negative. The results of direct agglutination reaction and absorption-elution test of the proband were both negative. Her Rh blood group was identified as RhD--. The results of the Rh blood grouping of her close relatives were normal. PCR-SSP detection showed that the RHCE genotypes of the proband and her close relatives were cE/cE and Ce/cE, respectively. Gene sequencing analysis showed that the RHCE genotypes of the proband and her close relatives were RHCE*cE (c.365C>A)/RHCE*cE (c.365C>A) and RHCE*Ce/RHCE*cE (c.365C>A), respectively. Pedigree analysis revealed that the variants in the proband were inherited from her father and mother, respectively. Homology modeling of RhCE*cE protein showed that the RhD-- type peptide chain with a significantly shortened C-terminal was encoded by only 121 amino acid resides, which was 296 amino acid resides shorter compared to the wild-type RhCE*cE peptide chain encoded by 417 amino acid residues. CONCLUSION Above results revealed the molecular biological mechanism of a RhD-- phenotype. The c.365C>A variant in the RHCE gene has rendered the RHCE*cE alleles invalid, which ultimately led to the RhD-- phenotype.
Humans ; Rh-Hr Blood-Group System/chemistry* ; Female ; Phenotype ; Male ; Alleles ; Pedigree ; Base Sequence ; Molecular Sequence Data ; Adult

Objective To explore the application efficacy of refined management on antimicrobial agents in a chest specialty hospital.Methods Multiple measures were implemented through perfecting management systems and processes,as well as conducting knowledge training,such as multi-dimensional specialized prescription reviewing,optimizing information systems,and implementing grid-based management of clinical pharmacist.A refined manage-ment mode for antimicrobial agents in a chest specialty hospital has been established.Antimicrobial management in-dicators for the whole hospital and each clinical specialty in 2023(before management)and 2024(after manage-ment)were analyzed.Results Compared with 2023,antimicrobial use rate among hospitalized patients in 2024 de-creased from 47.48％to 45.92％,and antimicrobial use density(AUD)decreased from 46.28 defined daily doses(DDDs)/(100 person·day)to 39.73 DDDs/(100 person·day).The ratio of antimicrobial cost to total drug cost decreased from 12.71％to 9.51％,and the per capita cost of antimicrobial use decreased from 1 344.18 Yuan to 975.52 Yuan.The use rate of prophylactic antimicrobial agents for class Ⅰ incision surgery increased from 84.48％to 89.52％,and the rationality rate increased from 69.25％to 94.53％.The management indicators of each clinical specialty improved significantly.Conclusion Through adopting a series of refined management measures,antimi-crobial management modes that are suitable for the actual situation of the hospital has been constructed,and obvious efficacy was achieved.Clinical application of antimicrobial agents is more standardized and rational.

Objective:To investigate the impact of plasma exchange (PE) on T lymphocytes and natural killer (NK) cells in patients after kidney transplantation.Methods:The study retrospectively collected clinical data from patients who underwent their first ABO-compatible kidney transplantation at the Kidney Transplantation Center of the First Affiliated Hospital of Zhengzhou University between January 1, 2021, and November 30, 2023. Based on whether the patients received PE after transplantation, they were divided into a PE group and a non-PE group. A total of 38 patients were included in the retrospective cohort study, 18 in the PE group (8 males and 10 females) and 20 in the non-PE group (11 males and 9 females), with median ages of 37.5 (19.0, 56.0) years and 40.7 (22.0, 60.0) years, respectively. The immune cell subpopulations of the two groups were analyzed and compared at three time points: before PE, after PE, and 7 to10 days post-PE (for the non-PE group, data were collected at equivalent time points). The primary focus was on the proportions and absolute counts of T cells, NK cells, and activated T cells (CD4CD25+T cells, CD8CD25+T cells, and CD8HLA-DR+T cells). A generalized estimating equation (GEE) was used for longitudinal analysis of these repeated measurements to evaluate the effects of PE on changes in these cell populations.Results:From 7 to 10 days after PE, the absolute count of CD4 T cells in the non-PE group increased from 42 (24, 152) cells/μl to 461 (309, 608) cells/μl, while in the PE group, it increased from 57 (11, 262) cells/μl to 212 (141, 576) cells/μl. According to the generalized estimating model, the difference in changes between the two groups was statistically significant ( Z=-2.9, P=0.004). For NK cell absolute counts, the non-PE group increased from 20 (16, 36) cells/μl to 43 (26, 81) cells/μl, while the PE group increased from 22 (12, 63) cells/μl to 90 (28, 142) cells/μl. The difference in changes between the two groups was also statistically significant ( Z=1.87, P=0.049). Regarding T cell activation, the proportion of CD8HLA-DR+T cells in the non-PE group decreased from 25.8% (18.4%, 45.0%) to 22.7% (15.2%, 31.6%), while in the PE group, it increased from 19.2% (8.1%, 33.2%) to 22.7% (15.2%, 31.6%). The difference in changes between the two groups was statistically significant ( Z=2.88, P=0.005). From 7 to 10 days after PE, there were significant differences in the changes of CD4CD25+T cells ( Z=2.70, P=0.009), CD8CD25+T cells ( Z=2.75, P=0.007), and CD8HLA-DR+T cells ( Z=4.04, P=0.001) between the PE group and the non-PE group. Conclusion:Plasma exchange after kidney transplantation can suppress the proliferation of CD4 T lymphocytes, increase the number of NK cells relatively, and maintain a high proportion of activated T lymphocytes.

Objective:To investigate the effect of plasma exchange (PE) in improving renal function among patients with delayed graft function (DGF)following kidney transplantation.Methods:This was a retrospective cohort study. Data were collected from 76 patients who underwent their first-time ABO-compatible kidney transplantation at the Kidney Transplantation Center of the First Affiliated Hospital of Zhengzhou University between January 1, 2022, and November 30, 2023, and subsequently developed DGF and received PE treatment. The cohort included 39 males and 37 females, with a median age of 37.5 years (30.8-46.0 years). Patients were categorized into three groups based on pre-PEhuman leukocyte antigen (HLA) antibody status: HLA antibody-negative group, HLA antibody-unknown group, and HLA antibody-positive group. Additionally, immunological status prior to PE categorized patients into four groups: (1) stable lymphocyte subsetand antibody profiles (21 cases); (2) elevated B cell proportions or antibody production, or increased antibody titers (26 cases); (3) increased proportions of T/NK/macrophages (13 cases); (4) increased proportions of T/NK/macrophages combined with antibody production or increased antibody titers (16 cases). The Wilcoxon rank-sum test was used to analyze changes in serum creatinine (Scr) levels and 24-hour urine output before and after PE in the different patient groups.Results:In the HLA antibody-negative group, Scr decreased significantly from 467 (260, 571) μmol/L before PE to 176 (123, 307) μmol/L after PE ( Z=-2.22, P<0.01), and 24-hour urine output increased significantly from 1 295 (480, 2 020) ml to 1 960 (1 632, 2 870) ml ( Z=1.76, P<0.01). In the HLA antibody-positive group, Scr decreased significantly from 420 (254, 660) μmol/L before PE to 177 (151, 287) μmol/L after PE ( Z=-3.26, P<0.01), and 24-hour urine output increased significantly from 1 355 (928, 1 925) ml to 2 440 (1 760, 2 797) ml ( Z=2.47, P<0.01). For patients grouped by immunological status, Scr levels in Group 2 decreased significantly from 407 (242, 699) μmol/L to 201 (157, 274) μmol/L ( Z=-2.92, P<0.001), while in Group 3, Scr decreased significantly from 330 (258, 594) μmol/L to 164 (152, 280) μmol/L ( Z=-1.97, P=0.017). Regarding 24-hour urine output, Group 2 showed a significant increase from 1 353 (850, 1 770) ml to 1 995 (1 740, 2 630) ml ( Z=3.43, P=0.003), while in Group 3, urine output increased from 1 850 (1 350, 2 480) ml to 2 200 (1 900, 2 850) ml, but the difference was not statistically significant ( Z=1.10, P>0.05). Conclusion:PE effectively reduces Scr levels and increase 24-hour urine output in patients with DGF after kidney transplantation, regardless of pre-treatment HLA antibody status. Additionally, for patients with post-transplant changes primarily in T/NK/macrophages without significant antibody changes, PE can also effectively reduce Scr levels.

Objective:To explore the molecular mechanism of a case with RhD-phenotype.Methods:A proband with RhD-phenotype who attended the clinic of the First Affiliated Hospital of Zhengzhou University on January 29, 2024 was selected as the study subject. Peripheral blood samples were collected from the proband (8 mL) and her close relatives (father, mother and brother; 3 mL each) for Rh phenotyping and irregular antibodies testing with gel card and test tube methods. Direct agglutination reaction and absorption-elution test were used to detect the c antigen on the red blood cells of the proband. PCR-sequence specific primers (PCR-SSP) typing and gene sequencing were used to determine the RHCE gene of the proband and her relatives. The origin of the proband′s variant was traced by pedigree analysis. Three-dimensional structural models of the wild-type RhCE*cE protein and the RhD-phenotype protein were constructed to predict the alterations of the RhD-phenotype protein caused by the variant. The procedures of this study were approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No.: 2023-KY-0870-003). Results:The red blood cells of the proband did not agglutinate with anti-C, anti-c, anti-E, and anti-e. The result of the serum irregular antibody test was negative. The results of direct agglutination reaction and absorption-elution test of the proband were both negative. Her Rh blood group was identified as RhD-. The results of the Rh blood grouping of her close relatives were normal. PCR-SSP detection showed that the RHCE genotypes of the proband and her close relatives were cE/cE and Ce/cE, respectively. Gene sequencing analysis showed that the RHCE genotypes of the proband and her close relatives were RHCE* cE (c.365C>A)/ RHCE* cE (c.365C>A) and RHCE* Ce/ RHCE* cE (c.365C>A), respectively. Pedigree analysis revealed that the variants in the proband were inherited from her father and mother, respectively. Homology modeling of RhCE*cE protein showed that the RhD-type peptide chain with a significantly shortened C-terminal was encoded by only 121 amino acid resides, which was 296 amino acid resides shorter compared to the wild-type RhCE*cE peptide chain encoded by 417 amino acid residues. Conclusion:Above results revealed the molecular biological mechanism of a RhD-phenotype. The c. 365C>A variant in the RHCE gene has rendered the RHCE* cE alleles invalid, which ultimately led to the RhD-phenotype.

The development of bio-psycho-social medical models has focused attention on the impact of chronic psychological stress on diseases.Chronic psychological stress falls within the category of emotional etiology in traditional Chinese medicine.This paper systematically reviews research progress into the chronic psychological stress-related combination of disease and syndrome,and analyzes the advantages and limitations of different models.We also provide insights into the direction and improvements of future research into chronic psychological stress-related disease pattern models.

Objective To investigate the patterns of syndrome changes and their possible material basis in mouse models of chronic psychological stress during the modeling process.Methods A chronic unpredictable mild stress(CUMS)method was employed to prepare a model of chronic psychological stress in mice.After 2 weeks of modeling,Xiaoyao powder(XYS group)and Sini powder(SNS group)were administered concurrently with the modeling process.General conditions,behavioral,and biochemical indicators were compared between the modeling mice(M4 and M6 group)and the mice treated for 2 weeks(S4 and X4 group)and 4 weeks(S6 and X6 group)after chronic psychological stress.Results Compared with M4 group mice,body mass,total distance and central distance in the open field test,serum NE concentration,and gastric Ghrelin expression were increased in S4 group and X4 group mice,and sugar water preference rate and serum D-xylose concentration were increased in S4 group mice.Compared with X4 group mice,total distance in the open field test and serum D-xylose concentration were increased in the S4 group mice.Compared with M6 group mice,body mass,serum NE concentration,serum D-xylose concentration,and gastric Ghrelin expression were increased in group S6 and X6 group mice;sugar water preference rate,total distance in the open field test,and active avoidance counts in the shuttle box test were increased in X6 group mice,while their serum CORT concentration was decreased.Compared with S6 group mice,body mass,total distance in the open field test,serum D-xylose concentration,and gastric Ghrelin expression in X6 group mice were increased.Conclusions During the process of modeling chronic psychological stress in mice,the traditional Chinese medicine syndrome evolved from liver qi stagnation to liver qi stagnation with spleen deficiency.The biological bases of the syndrome changes may be the combined changes in serum CORT and NE concentrations and the decrease in gastric Ghrelin levels.

Objective To investigate the patterns of syndrome changes and their possible material basis in mouse models of chronic psychological stress during the modeling process.Methods A chronic unpredictable mild stress(CUMS)method was employed to prepare a model of chronic psychological stress in mice.After 2 weeks of modeling,Xiaoyao powder(XYS group)and Sini powder(SNS group)were administered concurrently with the modeling process.General conditions,behavioral,and biochemical indicators were compared between the modeling mice(M4 and M6 group)and the mice treated for 2 weeks(S4 and X4 group)and 4 weeks(S6 and X6 group)after chronic psychological stress.Results Compared with M4 group mice,body mass,total distance and central distance in the open field test,serum NE concentration,and gastric Ghrelin expression were increased in S4 group and X4 group mice,and sugar water preference rate and serum D-xylose concentration were increased in S4 group mice.Compared with X4 group mice,total distance in the open field test and serum D-xylose concentration were increased in the S4 group mice.Compared with M6 group mice,body mass,serum NE concentration,serum D-xylose concentration,and gastric Ghrelin expression were increased in group S6 and X6 group mice;sugar water preference rate,total distance in the open field test,and active avoidance counts in the shuttle box test were increased in X6 group mice,while their serum CORT concentration was decreased.Compared with S6 group mice,body mass,total distance in the open field test,serum D-xylose concentration,and gastric Ghrelin expression in X6 group mice were increased.Conclusions During the process of modeling chronic psychological stress in mice,the traditional Chinese medicine syndrome evolved from liver qi stagnation to liver qi stagnation with spleen deficiency.The biological bases of the syndrome changes may be the combined changes in serum CORT and NE concentrations and the decrease in gastric Ghrelin levels.

Objective To explore the application efficacy of refined management on antimicrobial agents in a chest specialty hospital.Methods Multiple measures were implemented through perfecting management systems and processes,as well as conducting knowledge training,such as multi-dimensional specialized prescription reviewing,optimizing information systems,and implementing grid-based management of clinical pharmacist.A refined manage-ment mode for antimicrobial agents in a chest specialty hospital has been established.Antimicrobial management in-dicators for the whole hospital and each clinical specialty in 2023(before management)and 2024(after manage-ment)were analyzed.Results Compared with 2023,antimicrobial use rate among hospitalized patients in 2024 de-creased from 47.48％to 45.92％,and antimicrobial use density(AUD)decreased from 46.28 defined daily doses(DDDs)/(100 person·day)to 39.73 DDDs/(100 person·day).The ratio of antimicrobial cost to total drug cost decreased from 12.71％to 9.51％,and the per capita cost of antimicrobial use decreased from 1 344.18 Yuan to 975.52 Yuan.The use rate of prophylactic antimicrobial agents for class Ⅰ incision surgery increased from 84.48％to 89.52％,and the rationality rate increased from 69.25％to 94.53％.The management indicators of each clinical specialty improved significantly.Conclusion Through adopting a series of refined management measures,antimi-crobial management modes that are suitable for the actual situation of the hospital has been constructed,and obvious efficacy was achieved.Clinical application of antimicrobial agents is more standardized and rational.

The development of bio-psycho-social medical models has focused attention on the impact of chronic psychological stress on diseases.Chronic psychological stress falls within the category of emotional etiology in traditional Chinese medicine.This paper systematically reviews research progress into the chronic psychological stress-related combination of disease and syndrome,and analyzes the advantages and limitations of different models.We also provide insights into the direction and improvements of future research into chronic psychological stress-related disease pattern models.