Kidney transplantation is the most effective treatment for end-stage renal failure, and antibody-mediated rejection remains the leading cause of late allograft loss. Macrophages, as central effectors of innate immunity, play a crucial role in the initiation, progression and tissue damage of antibody-mediated rejection. This article reviews the spatiotemporal dynamic evolution of macrophage polarization status in different stages of antibody-mediated rejection, the fine regulation of key signaling pathways for macrophage polarization, macrophage related molecules and the application prospects of targeted macrophage therapy. In depth analysis of the research progress of macrophages in antibody-mediated rejection, aiming to provide important theoretical basis for the development of precision diagnostic tools based on macrophages and novel immune intervention targets for antibody mediated rejection, ultimately promoting the improvement of long-term prognosis in kidney transplantation.

Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

ObjectiveTo compare the histological staining performance of four various tissue fixatives, including a self-developed fixative, for preparing paraffin sections of rat eyeball tissue. MethodsTwenty 5-week-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups (n=5 per group). After anesthesia by intraperitoneal injection of Zoletil™ 50 at a dose of 45 mg/kg body weight, the rats were euthanized by exsanguination via the abdominal aorta. Bilateral eyeballs were carefully extracted intact and fixed for 72 h in 10% formaldehyde fixative, glutaraldehyde-formaldehyde mixed fixative, Davidson's fixative, and self-developed fixative, respectively. After fixation, the eyeballs were longitudinally sectioned along the optic nerve, with the portions containing the optic nerve preserved. The tissues were then dehydrated, embedded, and sectioned. Following hematoxylin and eosin (HE) staining, histological staining quality was compared among ocular structures including the cornea, lens, and retina. ResultsThe overall appearance of rat eyeballs showed marked shrinkage in the 10% formaldehyde group and the glutaraldehyde-formaldehyde group, whereas the eye morphology remained round and intact in the modified Davidson's fixative group and self-developed fixative group. The corneal stroma exhibited obvious rupture, and the cells were arranged in folded arrangement in the modified Davidson's fixative group, 10% formaldehyde group, and self-developed fixative group. In contrast, the corneal cells in the glutaraldehyde-formaldehyde group were neatly arranged, showing no rupture or folding, and exhibited clear staining, indicating the highest quality of corneal sectioning among all groups. In the 10% formaldehyde group, cracks were observed in the equatorial and cortical regions of the lens, but the lens fiber structure remained intact. The lenses in the modified Davidson's fixative group showed extensive rupture and detachment. The glutaraldehyde-formaldehyde group displayed only slight cracks at the equator. In the self-developed fixative group, mild red folding was limited to the peripheral lens region, with the remaining structures intact and unbroken. These findings indicated that the glutaraldehyde-formaldehyde and self-developed fixative groups achieved the best lens sectioning quality. The retina was severely detached from the choroid/sclera layer, with extensive rupture of each cellular layer in the 10% formaldehyde fixative group. In the glutaraldehyde-formaldehyde group, partial detachment between the retina and choroid/sclera was observed. The outer plexiform layer and nerve fiber layer showed separation with edema, while the cells in all layers were neatly arranged. In both the Davidson's fixative and the self-developed fixative groups, the retina remained intact without rupture, and no structural separation was observed in any layer. Both demonstrated advantages in preserving the integrity and orderly arrangement of all retinal layers; however, the self-developed fixative group exhibited greater contrast. ConclusionThe choice of fixative significantly affects the morphological preservation of various structures in the rat eye. The self-developed fixative demonstrates the best overall performance in maintaining overall eye morphology, the structural integrity of the lens, and retinal adhesion. For studies focusing solely on the corneal structure, the glutaraldehyde-formaldehyde mixed fixative is recommended. The 10% formaldehyde fixative exhibits unsatisfactory fixation effects for all the aforementioned ocular structures and is not recommended for detailed morphological studies of eyeball tissues.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.

ObjectiveTo observe the real‑world effectiveness and economic outcomes of Weishi Qingjin Formula （苇石清金方， WQF） in the treatment of adult community‑acquired pneumonia （CAP） with phlegm‑heat obstructing the lung syndrome. MethodsBased on a multicenter， real-world retrospective cohort study， clinical data were collected from hospitalized adult patients diagnosed with non‑severe CAP and phlegm‑heat obstructing the lung syndrome in 10 traditional Chinese medicine （TCM） hospitals in Jiangsu province. Patients were divided into an exposure group （those who received oral WQF） and a non‑exposure group （those who did not）. The following outcomes were compared between the two groups before and after treatment， which were remission rates of clinical symptoms including cough， expectoration （sputum volume， color， consistency）， and chest pain， levels of inflammatory markers including C‑reactive protein （CRP） and white blood cell count （WBC）， and the rate of pulmonary inflammatory absorption on chest CT. Subgroup analyses were performed based on age， gender， smoking status， presence of hypertension， and the severity of community-acquired pneumonia （CURB‑65） score， comparing the two groups in terms of cough remission rate， chest pain remission rate， and chest CT absorption rate. For health economic evaluation， cost‑effectiveness analysis was used to calculate the cost‑effectiveness ratio （CER） and incremental cost‑effectiveness ratio （ICER）. Univariate sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the results. ResultsA total of 647 patients in the exposure group and 1491 patients in the non-exposure group were included in the final statistical analysis. There was no statistically significant difference in length of hospital stay， gender， marital status， smoking history， bronchoscopy history， and comorbidities between the groups （P＞0.05）， but age， CURB-65 score， and antibiotic use. The exposure group had significantly higher remission rates of cough and sputum consistency than the non-exposure group （P＜0.05）. After adjusting for confounders using propensity score matching and logistic regression， the cough remission rate in the exposure group was 1.49 times that of the non-exposure group （P＜0.01）. No significant difference was observed between groups in the reduction rates of CRP and WBC， and in the rate of pulmonary inflammatory absorption on chest CT （P＞0.05）. Subgroup analyses revealed that the cough remission rate in the exposure group was significantly better than that in the non-exposure group except for patients aged ≥65 years， smokers， hypertensive patients， those using other type antibiotics or not using antibiotics， and those with a CURB-65 score ≥1 （P＜0.05）. Among smokers， the chest pain remission rate in the exposure group was 4.38 times that of the non-exposure group （P＜0.01）. No significant difference in chest CT absorption rate was found between groups across subgroups of gender， age， hypertension status， or antibiotic type （P＞0.05）. In terms of economic evaluation， CER was 10,877.60 CNY/case in the exposure group and 16,773.10 CNY/case in the non-exposure group. Compared to the exposure group， the non-exposure group incurred an additional 15,034.26 CNY to achieve one case of cough resolution， indicating a more favorable cost-effectiveness profile. Probabilistic sensitivity analysis yielded results consistent with the cost-effectiveness analysis， confirming the robustness of the findings. ConclusionWQF demonstrates significant efficacy in improving cough symptoms in the treatment of adult CAP with phlegm-heat obstructing the lung syndrome， and also exhibits favorable economic benefits.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.

ObjectiveTo observe the real‑world effectiveness and economic outcomes of Weishi Qingjin Formula （苇石清金方， WQF） in the treatment of adult community‑acquired pneumonia （CAP） with phlegm‑heat obstructing the lung syndrome. MethodsBased on a multicenter， real-world retrospective cohort study， clinical data were collected from hospitalized adult patients diagnosed with non‑severe CAP and phlegm‑heat obstructing the lung syndrome in 10 traditional Chinese medicine （TCM） hospitals in Jiangsu province. Patients were divided into an exposure group （those who received oral WQF） and a non‑exposure group （those who did not）. The following outcomes were compared between the two groups before and after treatment， which were remission rates of clinical symptoms including cough， expectoration （sputum volume， color， consistency）， and chest pain， levels of inflammatory markers including C‑reactive protein （CRP） and white blood cell count （WBC）， and the rate of pulmonary inflammatory absorption on chest CT. Subgroup analyses were performed based on age， gender， smoking status， presence of hypertension， and the severity of community-acquired pneumonia （CURB‑65） score， comparing the two groups in terms of cough remission rate， chest pain remission rate， and chest CT absorption rate. For health economic evaluation， cost‑effectiveness analysis was used to calculate the cost‑effectiveness ratio （CER） and incremental cost‑effectiveness ratio （ICER）. Univariate sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the results. ResultsA total of 647 patients in the exposure group and 1491 patients in the non-exposure group were included in the final statistical analysis. There was no statistically significant difference in length of hospital stay， gender， marital status， smoking history， bronchoscopy history， and comorbidities between the groups （P＞0.05）， but age， CURB-65 score， and antibiotic use. The exposure group had significantly higher remission rates of cough and sputum consistency than the non-exposure group （P＜0.05）. After adjusting for confounders using propensity score matching and logistic regression， the cough remission rate in the exposure group was 1.49 times that of the non-exposure group （P＜0.01）. No significant difference was observed between groups in the reduction rates of CRP and WBC， and in the rate of pulmonary inflammatory absorption on chest CT （P＞0.05）. Subgroup analyses revealed that the cough remission rate in the exposure group was significantly better than that in the non-exposure group except for patients aged ≥65 years， smokers， hypertensive patients， those using other type antibiotics or not using antibiotics， and those with a CURB-65 score ≥1 （P＜0.05）. Among smokers， the chest pain remission rate in the exposure group was 4.38 times that of the non-exposure group （P＜0.01）. No significant difference in chest CT absorption rate was found between groups across subgroups of gender， age， hypertension status， or antibiotic type （P＞0.05）. In terms of economic evaluation， CER was 10,877.60 CNY/case in the exposure group and 16,773.10 CNY/case in the non-exposure group. Compared to the exposure group， the non-exposure group incurred an additional 15,034.26 CNY to achieve one case of cough resolution， indicating a more favorable cost-effectiveness profile. Probabilistic sensitivity analysis yielded results consistent with the cost-effectiveness analysis， confirming the robustness of the findings. ConclusionWQF demonstrates significant efficacy in improving cough symptoms in the treatment of adult CAP with phlegm-heat obstructing the lung syndrome， and also exhibits favorable economic benefits.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Based on systematic review and consensus meetings of international multidisciplinary experts, the Transfusion and Anemia Expert Initiative—Control/Avoidance of Bleeding (TAXI-CAB) project team developed management strategies for platelet and plasma transfusion in critically ill children. This consensus presents five expert consensus statements and two recommendations addressing two key questions: 1) What Laboratory Tests and Physiologic Triggers Should Guide the Decision to Administer a Platelet or Plasma Transfusion in Critically ill Children? 2) What Product Attributes Are Optimal to Guide Specific Product Selection? This consensus provides guidance for decision-making regarding plasma and platelet transfusion in critically ill children in two aspects: relevant laboratory testing indicators and additional special properties of blood components. This article explains the rationale behind the recommendations in this part of the guideline, aiming to emphasize the need for clinicians to develop transfusion strategies based on multidimensional assessment, while calling for enhanced interdisciplinary collaboration and evidence-based research to optimize blood management in critically ill children, reducing the risk of over-transfusion and improving treatment outcomes. Furthermore, there remains an urgent need for further research to explore laboratory indicators associated with bleeding risk to guide transfusion therapy.

Objective:To discuss the effect of circadion rhythm gene TIMELESS(TIM)silencing on immune escape of the ovarian cancer cells,and to clarify its related mechanism.Methods:The CD8+T lymphocytes were isolated and identified by flow cytometry to detect the proportion of CD3+/CD8+cell subsets.The human ovarian cancer SK-OV-3 cells were cultured in vitro and divided into interference plasmid transfected with TIM small interfering(siRNA)(si-TIM),negative control plasmid(si-NC),programmed death ligand 1(PD-L1)over-expression plasmid(oe-PD-L1),and negative control plasmid(oe-NC)groups.The cells were further divided into blank control group(BC group,non-transfection),si-NC group(transfected with si-NC),si-TIM group(transfected with si-TIM),si-NC+oe-NC group(transfected with si-NC and oe-NC),and si-TIM+oe-PD-L1 group(transfected with si-TIM and oe-PD-L1).Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of TIM mRNA and protein in the SK-OV-3 cells to verify TIM gene silencing.The transfected SK-OV-3 cells were co-cultured with activated CD8+T lymphocytes and divided into BC group(SK-OV-3 cells cultured alone),BC/T group,si-NC/T group,si-TIM/T group,si-NC+oe-NC/T group,and si-TIM+oe-PD-L1/T group.CCK-8 method was used to detect the survival rates of the SK-OV-3 cells in various groups;flow cytometry was used to detect the apoptotic rates of the SK-OV-3 cells and positive expression rate of PD-L1 on surface of the cells in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α)in the co-culture supernatant;lactate dehydrogenase(LDH)release assay was used to detect the cytotoxicity of the CD8+T lymphocytes in various groups;RT-qPCR method was used to detect the expression levels of TIM and PD-L1 mRNA in the SK-OV-3 cells in various groups;Western blotting method was used to detect the expression levels of TIM and PD-L1 proteins in the SK-OV-3 cells in various groups.Results:After scparated with immune magnetic bead method,the proportion of CD8+T lymphocyte(CD3+/CD8+)subsets was(96.56%±0.59%),indicating high purity of the extracted CD8+T lymphocytes.Compared with BC group,the expression levels of TIM mRNA and protein in the cells in si-TIM group were significantly decreased(P<0.01),suggesting successful TIM gene silencing in the ovarian cancer SK-OV-3 cells.The CCK-8 results showed that compared with BC group,the survival rate of the SK-OV-3 cells in BC/T group was significantly decreased(P<0.01);compared with BC/T group,the survival rate of the SK-OV-3 cells in si-TIM/T group was significantly decreased(P<0.01).The flow cytometry results showed that compared with BC group,the apoptotic rate of the SK-OV-3 cells in BC/T group was significantly increased(P<0.01);compared with BC/T group,the apoptotic rate of the SK-OV-3 cells in si-TIM/T group was significantly increased(P<0.01);compared with si-TIM/T group,the apoptotic rate of the SK-OV-3 cells in si-TIM+oe-PD-L1/T group was significantly decreased(P<0.01).Compared with BC group,the positive expression rate of PD-L1 on surface of the SK-OV-3 cells in si-TIM group was significantly decreased(P<0.01).The ELISA results showed that compared with BC/T group,the levels of IFN-γ and TNF-α in the culture supernatant in si-TIM/T group were significantly increased(P<0.01);compared with si-TIM/T group,the levels of IFN-γ and TNF-α in the supernatant in si-TIM+oe-PD-L1/T group were significantly decreased(P<0.01).The LDH release assay results showed that compared with BC/T group,the cytotoxicity of the CD8+T lymphocytes in si-TIM/T group was significantly increased(P<0.01);compared with si-TIM/T group,the cytotoxicity of the CD8+T lymphocytes in si-TIM+oe-PD-L1/T group was significantly weakened(P<0.01).The RT-qPCR and Western blotting results showed that compared with BC group,the expression levels of PD-L1 mRNA and protein in the SK-OV-3 cells in si-TIM group were significantly decreased(P<0.01);compared with si-TIM group,the expression level of PD-L1 protein in the cells in si-TIM+oe-PD-L1 group was significantly increased(P<0.01).Conclusion:TIM gene silencing enhances the cytotoxic effect of CD8+T lymphocytes on ovarian cancer SK-OV-3 cells and inhibits immune escape,and its mechanism may be related to the regulation of PD-L1 protein expression.