As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

Xenotransplantation is one of the effective ways to overcome the shortage of donor organs. However, the molecular incompatibility between xenotransplantation donors and recipients can cause rejection, which greatly limits the clinical application of xenotransplantation. In recent years, researchers have deeply explored the mechanism of xenotransplantation rejection through xenotransplantation models of pig-to-monkey and pig-to-brain death recipients, and found that the innate immune system plays an important role in rejection. Macrophages, as phagocytes in the innate immune system, not only damage xenografts through phagocytosis but also interact with other immune cells to influence the immune microenvironment of xenotransplantation. However, due to the heterogeneity of macrophages, their phenotypes and functions in xenotransplantation rejection remain unclear. Therefore, it is necessary to further explore the role of macrophages in xenotransplantation rejection. This article reviews the latest research progress of macrophages in xenotransplantation rejection, aiming to explore the mechanisms of macrophages in xenotransplantation rejection and provide references for future research.

CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

Objective To explore the clinical efficacy and safety of modified PPH combined with partial internal anal sphincterotomy in the treatment of circular mixed hemorrhoids.Methods Patients with annular mixed hemorrhoids were divided into two groups by a completely randomized controlled method.54 patients in the experimental group were treated with modified PPH combined with partial internal anal sphincterotomy,while 51 patients in the control group were treated with conventional PPH.The postoperative indicators,perioperative and long-term complication rates of the two groups were compared,and the clinical efficacy and safety were observed.Results The operation time in the experimental group was(48.35±4.37)minutes,which was higher than that in the control group(36.42 ±6.21)minutes(P＜0.05).The incidence of postoperative anastomotic stenosis in the experimental group was 1.9％,lower than 15.6％ in the control group(P＜0.05).Anal pain,urinary retention,first defecation time,long-term anal distention,the experimental group was significantly better than the control group,the difference was statistically significant(P＜0.05);The hospitalization time in the experimental group(4.8±0.62)days was not significantly different from that in the control group(5.1±0.54)days(P＞0.05).The amount of intraoperative bleeding and anastomotic bleeding in the experimental group[(17.28±2.22)ml,3.7％]were not significantly different from those in the control group[(16.75± 2.13)ml,3.9％](P＞0.05).Conclusion Compared with conventional PPH,the modified PPH combined with partial internal anal sphincterotomy slightly increases the operation time,but does not increase the risk of anastomotic bleeding,the incidence of rectal fistula,the amount of surgical bleeding,and the length of hospital stay.It can significantly improve postoperative anal pain,urinary retention,long-term distention symptoms,shorten the time of first defecation,ease the difficulty of defecation,and significantly reduce postoperative anastomotic stenosis,The long-term efficacy and safety are good.

Objective:To investigate the level of serum vascular endothelial growth factor (VEGF) and its correlation with clinical symptoms in patients with first-episode drug-naive schizophrenia patients of different genders.Methods:From January 2016 to October 2019, a total of 81 first-episode drug-naive schizophrenia patients(patient group, 41 male, 40 female) and 64 healthy controls (control group, 40 male, 24 female) were included in this study.The serum level of VEGF was detected with flow cytometric bear array (CBA). Positive and negative symptom scale (PANSS) was used to evaluate the relevant clinical symptoms of patients.SPSS 22.0 software was used for statistical analysis.Independent sample t-test and nonparametric test were used for comparison between groups.The relationship between VEGF and clinical variables was analyzed by Pearson correlation analysis and Spearman correlation analysis. Results:The level of serum VEGF in the patient group was significantly lower than that in the control group(148.08(75.89, 208.61)pg/mL, 179.94(99.14, 318.41)pg/mL, Z=-2.20, P=0.028). The total PANSS score((82.71±17.30), (73.45±16.36), t=2.473, P=0.016)and cognitive score((7.88±3.36), (6.23±2.81), t=2.402, P=0.019) in male patients were higher than those in female patients.There was a negative correlation between VEGF level and PANSS negative symptom score in the patient group( r=-0.228, P=0.041), as well as significant negtive correlation between VEGF level and cognitive score in male patients( r=-0.425, P=0.007). Conclusion:The level of serum VEGF is reduced in first-episode patients with schizophrenia, which influences their negative symptom. Moreover, the decline in serum VEGF level is implicated in cognitive impairments in male patients with first-episode schizophrenia.

Objective:To explore the preparation and preliminary research on the characteristics of modified nano-bioglass hydrogel.Methods:(1) The nano-bioglass suspension was prepared by adding 67 mL nano-silica suspension into 400 mL saturated calcium hydroxide solution, and its suspension stability was observed. (2) The hydrogel with final mass fraction of 10% gelatin and 1% sodium alginate was prepared and set as control group. On the basis of the hydrogel in control group, the nano-bioglass suspension prepared in experiment (1) was added to prepare the hydrogel with the final mass fraction of 0.5% bioglass, 10% gelatin, and 1% sodium alginate, and the hydrogel was set as the experimental group. The gelling time at 4 and 25 ℃and the dissolution time at 37 ℃ of hydrogel in 2 groups were recorded, and the gelation at 4 and 25 ℃and dissolution condition at 37 ℃of the hydrogel in 2 groups were observed. The hydrogel in 2 groups were collected and cross-linked with 25 g/L calcium chloride solution after cold bath at 4 ℃, and the compression modulus was measured by Young′s modulus tester. In addition, the hydrogel in 2 groups were collected and cross-linked as before, and freeze-drying hydrogel was made at -20 ℃. The relative volumes were measured and the porosity of hydrogel in 2 groups was calculated. The number of sample in the experiment was 3. (3) Fibroblasts (Fbs) were isolated and cultured from 12 C57BL/6J mice of 24 hours old and the morphology was observed by inverted microscope, and the third passage of Fbs were cultured for the following experiment. Fbs were collected to make single cell suspension with the cell concentration of 1×10 5/mL. The single cell suspension was divided into experimental group and control group according the random number table (the same grouping method below), which were added with hydrogel in experimental group and control group prepared in experiment (2), respectively. At culture hour 12, 24, and 48, cells of 3 wells in each group were collected to detect the survival rate by cell counting kit 8 method. (4) The third passage Fbs were collected to prepare the single cell suspension with the cell concentration of (3.0~4.5)×10 7/mL, which was divided into experimental group and control group, with 1 tube in each group. The single cell suspension in 2 groups were added with green fluorescent probe DIO for staining and then added with 9 mL hydrogel in experimental group and control group prepared in experiment (2), respectively. The mixed solution of Fbs and hydrogel in 2 groups was cross-linked as before to make cell-loaded hydrogel. On culture day 3, the survival of cells in the hydrogel was observed by laser confocal microscope. The cell-loaded hydrogel was prepared as before and without added with green fluorescent probe DIO. On culture day 7, the adhesion and extension of cells in the hydrogel were observed by scanning electron microscope. (5) Twelve 6-week-old female BALB/c-nu nude mice were collected and divided into experimental group and control group, with 6 mice in each group. A round full-thickness skin defect wound with diameter of 1 cm was made on the back of each mouse. Immediately after injury, one cell-loaded hydrogel block in the experimental group and the control group prepared in experiment (4) was placed in the wound of each mouse in the experimental group and the control group, respectively. On post injury day (PID) 7 and 14, 3 nude mice in each group were sacrificed to collect the wound and wound margin tissue, which was stained with hematoxylin-eosin to observe the wound healing. Data were statistically analyzed with independent sample t test. Results:(1) The nano-bioglass particles could be uniformly dispersed in water and had good suspension stability. (2) The hydrogels of the 2 groups were molten at 37 ℃, and no precipitation of particle was observed. The dissolving time of the hydrogel in the experimental group and the control group at 37 ℃ was 5 and 10 min, respectively. The gelation time of the hydrogel in the experimental group and the control group at 25 ℃ was 30 and 180 min, respectively, and the gelation time of the 2 groups at 4 ℃ was 5 and 10 min, respectively. The compression modulus of hydrogel in the experimental group was (53±6) kPa, which was significantly higher than (23±6) kPa in the control group ( t=6.364, P<0.01). The porosity of the hydrogel in the experimental group was (86.1±2.1)%, which was similar to (88.2±4.4)% in the control group ( t=1.210, P>0.05). (3) The cells were in long fusiform, and the proportion of nuclei was high, which was accorded with the morphological characteristics of Fbs. At culture hour 12, 24, and 48, the survival rate of cells in the experimental group was (84±4)%, (89±4)%, and (130±10)%, which was similar to (89±5)%, (90±4)%, and (130±11)% in the control group, respectively ( t=1. 534, 0.611, 0.148, P>0.05). (4) On culture day 3, the cells in the two groups had complete morphology in the hydrogel, no nuclear lysis or disappearance were observed, the cytoplasm remained intact, and the fluorescence intensity of the cells in the experimental group was significantly stronger than that in the control group. On culture day 7, the cells in the experimental group and the control group adhered and stretched in the hydrogel, and the number of cells in the experimental group adhered to the hydrogel was significantly more than that in the control group. On PID 7, the wound area of the nude mice in the control group and the experimental group were reduced, the reduction area of mice in the experimental group was more obvious, and a large amount of inflammatory cells were seen in and around the wound in the 2 groups. On PID 14, the wound area of the nude mice in the control group was larger than that of the experimental group, and the number of inflammatory cells in and around the wound was significantly more than that in the experimental group. Conclusions:Nano-bioglass hydrogel possesses good physical, chemical, and biological properties, cell loading potential, and the ability to promote wound healing, which means it has a good potential in clinical application.

Objective: To explore the correlation between serum high density lipoprotein (HDL) levels and cognitive function in patients with bipolar disorder. Methods: A total of 99 patients with bipolar disorder were enrolled from the inpatient of Suzhou Guangji Hospital.Serum HDL levels were measured by enzymatic colourimetry.Cognitive function was assessed by the repeatable battery for the assessment of neuropsychological status (RBANS). The relationship between serum high density lipoprotein and cognitive function was analyzed by correlation analysis and stepwise multiple regression analysis. Results: Serum HDL levels ((1.39±0.55)mmol/L)were positively correlated with the RBANS total score (68.92±12.48)(r=0.238, P=0.034) and language score(80.59±15.97) (r=0.239, P=0.033) in patients with bipolar disorder.Stepwise multiple regression analysis showed that serum HDL level was the influencing factor of total score of RBANS(β=4.791, t=2.151, P=0.035)and speech function(β=7.363, t=2.247, P=0.027). Conclusion Serum HDL levels can influence cognitive function, especially speech function in patients with bipolar disorder.

Objective:To examine the clinical value of combining indocyanine green (ICG) fluorescence navigation with blue dye in sen-tinel lymph node biopsy (SLNB) for patients with breast cancer. Methods:A total of 89 patients with early-stage breast cancer who met the inclusion criteria were admitted at Shantou Central Hospital, Guangdong from May 2013 to April 2014. In phase one, ICG and blue dye were applied in all 53 patients, and then SLNB and axillary lymph node dissection (ALND) were performed based on fluores-cence signal or visual sense of the lymph nodes. In phase two, 36 patients with early-stage breast cancer were included. ALND was omitted when sentinel lymph nodes were frozen showing negative result. Rates of detection, accuracy, and false-negative were calcu-lated. Results:A total of 89 patients were monitored, of which the total rate of SLNB detection was 96.6%(86/89). In the validation pe-riod, the rates of detection, accuracy, and false-negative were 94.3%(50/53) 98.0%(49/50), and 2.6%(1/38), respectively. In the alter-ative period, the rates of detection reached 100%. Of the 196 sentinel lymph nodes, 179 showed fluorescence signal, 142 exhibited blue dying, 54 only demonstrated fluorescence signals, and 45 demonstrated metastasis with five signaling fluorescence. About 24.7%of patients were diagnosed with SLN metastasis (22/89), where SLNB in two patients showed fluorescence signal but without blue dye. No ipsilateral lymph node relapsed were observed during a median follow up of 25 months. Conclusion:Combination of ICG fluores-cence navigation with blue dye in SLNB is safe for patients with breast cancer.