Objective: To analyze characteristics of hepatitis B infection in HBsAg-/HBV DNA+ blood donors in Taiyuan, so as to provide evidence for adjusting blood screening strategies. Methods: Blood samples of HBsAg-/HBV DNA+ donors were tested using enzyme-linked immunosorbent assay (ELISA), chemiluminescence assay, nucleic acid qualitative test, and nucleic acid quantitative test. Data on HBsAg-/HBV DNA+ donors in Taiyuan region from January 1, 2016 to December 31, 2024 were statistically analyzed to evaluate the detection rate, demographic characteristics, influencing factors of detection rate, nucleic acid quantitative results, and serological patterns of HBsAg-/HBV DNA+ donors. Results: From January 1, 2016 to December 31, 2024, 991 565 donor samples underwent nucleic acid testing in Taiyuan. A total of 309 HBsAg-/HBV DNA+ samples were detected, resulting in an HBsAg-/HBV DNA+ detection rate of 3.12 per 10 000. The detection rate varied significantly across different years (P<0.05). Males had a significantly higher HBsAg-/HBV DNA+ detection rate than females, first-time donors had a higher rate than repeat donors, and whole blood donors had a higher rate than apheresis donors (P<0.05). The detection rate also differed significantly among age groups (P<0.05). Logistic regression analysis showed that gender, age, donation frequency, and donation type were all influencing factors for HBsAg-/HBV DNA+ detection (all P<0.05). The predominant serological patterns among HBsAg-/HBV DNA+ donors were HBsAb+/HBcAb+ (43.69%, 135/309) or HBcAb+ alone (24.27%, 75/309). Viral load was detectable in 53.40% (165/309) of the HBsAg-/HBV DNA+ donors. Among these, 61.21% (101/165) donors had a viral load<20 IU/mL, and 94.55% (156/165) had a viral load<200 IU/mL. Donors with viral load<200 IU/mL primarily exhibited HBsAb+/HBcAb+ (41.67%, 65/156) or HBcAb+alone (36.54%, 57/156) serological patterns. Conclusion: The prevalence of HBsAg-/HBV DNA+ is low among blood donors in Taiyuan. Higher detection rates were observed in the 46-55 years age group, males, first-time donors, and whole blood donors. HBsAg-/HBV DNA+ donors exhibit specific serological patterns and generally have low viral loads, indicating a potential residual transfusion risk. It is recommended to add HBcAb testing, together with high-sensitivity nucleic acid testing technologies and donor follow-up, to ensure blood safety and guide donor reentry.

AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

Objective To optimize the filtration process before inactivation in the preparation of enterovirus 71(EV71)inactivated vaccine, screen high recovery filters, and evaluate their effects on viral structural proteins and immunogenicity.MethodsBy comparing the recovery rates of feed solution, antigen, and protein processed by four different filters, the optimal filter was selected. SDS-PAGE and Western blot were used to analyze the changes in viral structural proteins before and after filtration. The prepared bulk solution and aluminum hydroxide adjuvant were adsorbed and divided into five groups to intraperitoneally immunize female BALB/c mice, including unfiltered high-dose group(4. 5 μg/dose), unfiltered low-dose group(1. 5 μg/dose), filtered high-dose group, filtered low-dose group and blank control group(1. 05 mg/dose aluminum hydroxide adjuvant), with 10 mice in each group. The mice were immunized twice on day 0 and day 14. Blood samples were collected on day 0(before immunization), day 14 and day 28. The neutralizing antibody titer of immunized animals was detected by micro cytopathic inhibition method, and then the effect of filtration process on virus immunogenicity was evaluated.ResultsFilter 2 exhibited the highest antigen and protein recovery rates among the four filters, at 96. 10% and94. 64%, respectively. There was no significant difference in the proportion of viral structural proteins(VP0, VP1, VP2, VP3)before and after filtration(t = 1. 527, 0. 693, 1. 113 and 2. 416, P = 0. 201, 0. 526, 0. 328 and 0. 073, respectively). There was no significant difference in immunogenicity of EV71 vaccine before and after filtration on day 14 and day 28 between the low-dose groups as well as the high-dose groups(low-dose groups: t = 1. 067 and 0. 574, P = 0. 300 and 0. 573, respectively;high-dose groups: t = 0. 249 and 0. 110, P = 0. 806 and 0. 914, respectively), indicating that the addition of filtration process had no effect on the immunogenicity of EV71 vaccine.ConclusionAdding a filtration process before inactivation has no effect on virus structure and immunogenicity, which meets the requirements of WHO for vaccine safety.

Objective To establish an "human serum - porcine aortic endothelial cells (PAEC) - human platelets" in vitro model and explore the mechanism of xenotransplantation-related coagulation dysfunction mediated by immune complexes - platelet FcγRⅡa (CD32a) receptor. Methods Healthy human serum was co-incubated with PAEC to prepare the supernatant containing immune complexes, which was then used to stimulate healthy human platelets, or directly treated with the serum of xenogeneic liver transplant recipients. Flow cytometry was used to detect platelet activation markers CD62P and surface IgG binding levels, and the platelet adhesion function was evaluated by platelet-PAEC adhesion experiments. CD32a blocking antibody IV.3 and SYK blocker SKYIN 4 were used to clarify the signaling pathways. Results The supernatant from the co-incubation of healthy human serum and PAEC could significantly induce platelet activation and endothelial adhesion. The use of the serum from xenogeneic liver transplant recipients could also significantly induce platelet activation. Antibody IV.3 and SYK blocker SKYIN 4 could significantly inhibit these effects. Conclusions In xenotransplantation, the immune complexes formed by human serum antibodies and porcine endothelial antigens may induce abnormal platelet activation through the platelet CD32a receptor, which is an important mechanism of non-complement-dependent post-transplant coagulation dysfunction, providing a new target for the intervention of coagulation complications in xenotransplantation.

In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

Objective To examine the safety, efficacy and durability of totally endoscopic minimally invasive (TEMI) mitral valve repair in Barlow’s disease (BD). Methods A retrospective study was performed on patients who underwent mitral valve repair for BD from January 2010 to June 2021 in the Guangdong Provincial People’s Hospital. The patients were divided into a MS group and a TEMI group according to the surgery approaches. A comparison of the clinical data between the two groups was conducted. Results A total of 196 patients were enrolled, including 133 males and 63 females aged (43.8±14.9) years. There were 103 patients in the MS group and 93 patients in the TEMI group. No hospital death was observed. There was a higher percentage of artificial chordae implantation in the TEMI group compared to the MS group (P=0.020), but there was no statistical difference between the two groups in the other repair techniques (P>0.05). Although the total operation time between the two groups was not statistically different (P=0.265), the TEMI group had longer cardiopulmonary bypass time (P<0.001) and aortic clamp time (P<0.001), and shorter mechanical ventilation time (P<0.001) and postoperative hospitalization time (P<0.001). No statistical difference between the two groups in the adverse perioperative complications (P>0.05). The follow-up rate was 94.2% (180/191) with a mean time of 0.2-12.4 (4.0±2.4) years. Two patients in the MS group died with non-cardiac reasons during the follow-up period. The 3-year, 5-year and 10-year overall survival rates of all patients were 100.0%, 99.2%, 99.2%, respectively. Compared with the MS group, there was no statistical difference in the survival rate, recurrence rate of mitral regurgitation, reoperation rate of mitral valve or adverse cardiovascular and cerebrovascular events in the TEMI group (P＞0.05). Conclusion TEMI approach is a safe, feasible and effective approach for BD with a satisfying long-term efficacy.

Gastric cancer is a common malignant tumor of the digestive tract and can be classified as “fullness of the stomach”， “epigastric pain”， “noise” and other categories in the field of traditional Chinese medicine. Sijunzi decoction is composed of Panax ginseng， Poria cocos， Atractylodes macrocephala， and honey-fried Glycyrrhiza uralensis， and it has the effect of tonifying qi and strengthening the spleen. This article summarizes the active ingredients， mechanism of action， and clinical application research progress of Sijunzi decoction in treating gastric cancer. The results show that the main active ingredients of Sijunzi decoction include ginsenosides， atractylenolide， pachymic acid， glycyrrhizic acid， etc.； Sijunzi decoction and its effective ingredients can play an anti-gastric cancer role by inhibiting the proliferation of gastric cancer cell， inducing apoptosis of gastric cancer cell， enhancing gastric cancer cell chemotherapy sensitivity， and inhibiting invasion and metastasis of gastric cancer cell. In addition， Sijunzi decoction can enhance the efficacy of chemotherapy drugs， strengthen the immune function of the body and lower serum cancer marker levels during the clinical treatment of gastric cancer.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*