Objective To compare the outcomes of transplant kidneys and patient survival between simultaneous pancreas-kidney transplantation(SPKT)recipients and deceased donor kidney transplant(DDKT)recipients in patients with type 2 diabetes mellitus(T2DM)complicated with end-stage renal disease(ESRD),and to analyze the risk factors affecting patient survival post-SPKT.Methods Clinical and prognostic data of patients who underwent kidney transplantation from January 27,2003,to January 1,2021,were retrieved from the United Network for Organ Sharing(UNOS)database.A total of 50 230 cases were selected based on inclusion criteria,with 48 669 cases in DDKT group and 1561 cases in SPKT group.Kaplan-Meier analysis was employed to compare transplant kidney and patient survival between the two groups,and propensity score matching(PSM)was utilized to balance confounding factors between the groups.Cox regression model was used to analyze independent risk factors affecting patient survival post-SPKT.Results Compared with DDKT group,recipients in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),shorter dialysis and transplant waiting times(P<0.001),a higher percentage of private medical insurance(P<0.001),a lower proportion of previous transplants(P<0.001),a younger age at diabetes diagnosis(P<0.001),and a lower incidence of peripheral vascular disease(P=0.033).Compared with DDKT group,the donors in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),and a lower prevalence of hypertension and diabetes history(P<0.001).In terms of transplant-related factors,the SPKT group had a shorter donor kidney cold ischemia time(P<0.001),a higher degree of HLA mismatch(P<0.001),and a lower Kidney Donor Profile Index(KDPI)(P<0.001)when compared with DDKT group.The SPKT group had lower serum creatinine levels at discharge(P<0.001),lower rates of postoperative delayed graft function(DGF)and acute rejection(AR)(P<0.001),but longer hospital stays(P<0.001)when compared with DDKT group.Kaplan-Meier survival analysis curves,both original and after propensity score matching(PSM),consistently showed significantly higher transplant kidney and patient survival rates in SPKT group compared with DDKT group(P<0.001).Cox regression model analysis indicated that recipient age,recipient race,donor age,and donor kidney cold ischemia time were independent risk factors influencing patient survival post-SPKT.Conclusions For ESRD patients with T2DM,SPKT offers improved long-term graft and patient survival rates compared with DDKT.Recipient age,recipient ethnicity,donor age,and cold ischemia time for the donor's kidney are independent risk factors affecting post-SPKT patient survival.

Post-stroke cognitive impairment(PSCI)is a prevalent functional impairments following stroke that seriously affects patients'quality of life and daily activities.Studies indicate a close relationship between intestinal microflora dysbiosis and central nervous system diseases.Intestinal microflora profoundly impacts on human physiological health,contributing to the stability of nervous,metabolic and immune systems through regulation of the gut-brain axis.An increasing number of studies confirmed the important role of the gut microbiome-gut-brain axis in the occurrence and development of stroke and its associated PSCI,and regulation of microbiome-gut-brain could be potential target to treatment of PSCI.This review summarizes research progress on gut microbiome-gut-brain axis and PSCI to provide a reference for exploration of related mechanisms and clinical prevention and treatment strategies.

Objective:To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts.Methods:C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry.Results:On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion:High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

Objective:To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts.Methods:C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry.Results:On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion:High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

This study investigated the characteristics of gut microbiota imbalance in patients with infectious diarrhea caused by various pathogenic infections,and the role of Bacteroides in maintaining homeostasis in the intestinal environment.The gut microbiota in patients with diarrhea caused by pathogenic infections,such as viral and bacterial infections,was determined through full-length 16S rRNA amplicon sequencing.Patients with diarrhea were grouped and analyzed according to the presence of single bacterial infection,single viral infection,mixed infection,or Clostridioides difficile infection.Bacteroides had the highest absolute number and relative abundance in the gut microbiota in healthy people,whereas patients with infectious diar-rhea showed lower relative abundance of Bacteroides at each phylum/order/family/genus taxonomic level.Alpha diversity anal-ysis indicated no significant differences among groups.NMDS and PCoA indicated formation of distinct clusters in the control group compared with the different infectious diarrhea groups.The diversity of the gut microbiota was higher in the control group than the infectious diarrhea groups.Patients with infec-tious diarrhea caused by different pathogens showed differing predominant gut microbiota.Bifidobacterium predominated in the single viral infection group,Streptococcus predominated in the single bacterial infection group,and Lachnoclostridium predominated in the mixed infection group.Escherichia and Klebsiella were the major gut microbiota in the C.difficile infection group.Meanwhile,the dominant gut microbiota in the healthy population was Bacteroides.COG function prediction revealed that the healthy control group formed a distinct cluster from the different infection groups.The functions of defense mechanisms,cell wall synthesis,protein modification,cellular differentiation,and replication and recombination were signifi-cantly diminished in all infectious diarrhea groups.In general,patients with infectious diarrhea caused by different pathogens showed dysbiosis,with diminished gut microbiota diversity and the emergence of related biomarkers.Our findings indicated that Bacteroides has a key role in maintaining the homeostasis of the human intestinal environment,thus providing new ideas for the subsequent treatment of infectious diarrhea and research in other fields.

Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

OBJECTIVE: To analyze the correlation between Cobb angle and spinous process angle (SPA) on X-ray film and body surface in patients with mild to moderate adolescent idiopathic scoliosis(AIS). To explore the possibility of linear SPA to assess scoliosis. METHODS: Retrospective study for correlation of Cobb angle and linear SPA on X-ray film. AIS patients treated and taken full spine anteroposterior X-ray from January 2019 to December 2021 were analyzed correlation of Cobb angle and linear SPA on X-ray film. Prospective study for correlation of Cobb angle and body linear SPA. AIS patients treated and taken full spine anteroposterior X-ray from December 1 to December 9 this year were analyzed correlation of Cobb angle and body linear SPA. RESULTS: A total of 113 AIS patients with age an average of (14.02±2.16) years old(ranged from 10 to 18 years old) were recruited in retrospective study, involving 26 males and 87 females;there were 71 patients with mild AIS and 42 patients with moderate AIS. Cobb angle in AIS patients was significantly inversely associated with SPA(r=-0.564, P<0.001), the linear regression equation was:Cobb angle=169.444-0.878×SPA. Cobb angles in patients with mild scoliosis were significantly and inversely associated with SPA(r=-0.269, P=0.012), the linear regression equation was:Cobb angle=46.832-0.185×SPA. Cobb angles in patients with moderate scoliosis were also clearly correlated with SPA(r=-0.417, P=0.003), the linear regression equation was:Cobb angle=113.889-0.516×SPA. Thirty-eight patients were recruited in prospective study. The mean Cobb angle and body linear SPA were(18.70±6.98)°, ranged from 11.3° to 36.0° and (170.34±4.57)°, ranged from 162.1° to 177.7° respectively. There was significantly negative correlation(r=-0.651, P<0.001), the linear regression equation is:Cobb angle=187.91-0.99×SPA. CONCLUSION Linear SPA on X-ray film or on the body was significantly negatively correlated with Cobb angles, but the regression equation fits poorly, so it's not suitable for diagnosis of scoliosis;however, linear SPA is appropriate for self-controlled assessment of scoliotic therapy or for dynamic assessment of spinal flexibility.
Male ; Female ; Humans ; Adolescent ; Child ; Scoliosis/diagnostic imaging* ; Prospective Studies ; Retrospective Studies ; Spine/diagnostic imaging* ; Kyphosis

OBJECTIVE: To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism. METHODS: DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 μmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC₅₀) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture. RESULTS: Baicalin inhibited the proliferation of DB cells in a dose-dependent manner (r=-0.99), and the IC₅₀ was 20.56 μmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased (P<0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway (P<0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased (P<0.05), and the content of ROS in the NAC group was significantly decreased (P<0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production (P<0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group (P<0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME (P<0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production. CONCLUSION Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/pharmacology* ; Pyroptosis ; Cell Line ; RNA, Messenger ; Lymphoma, Large B-Cell, Diffuse

OBJECTIVE: To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients. METHODS: Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression. RESULTS: Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%，P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05). CONCLUSION Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.
Humans ; Bone Marrow/pathology* ; Polycythemia Vera ; Hyperplasia/pathology* ; Granulocytes/pathology* ; Janus Kinase 2/genetics* ; Risk Factors ; Lipoproteins, LDL ; Polycythemia/pathology*