Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

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

OBJECTIVE To compare the clinical and microbiological characteristics of patients with bloodstream in-fection(BSI)and to summarize the risk factors for death in these patients.METHODS Clinical data of 528 patients with BSI admitted to Xijing Hospital,the Fourth Military Medical University from Jul.2018 to Feb.2023 were collected.The clinical characteristics,pathogens,antibacterial drug therapy and 28-day case-fatality rate of the pa-tients with BSI were analyzed.RESULTS Among the 528 patients with BSI,there were 139 patients with commu-nity-associated infection,69 patients with health care-associated infection,and 320 patients with hospital-associat-ed infection.The predominant pathogens isolated from patients with community-associated infection and health care-associated infection were Escherichia coli(53.96％and 42.03％,respectively),while Klebsiella pneumoni-ae was the main pathogen in patients with hospital-associated infection(24.38％),with a wide variety of major pathogens identified.The drug resistance profiles of E.coli and K.pneumoniae isolated from patients with health care-associated infection were similar to those isolated from patients with hospital-associated infection but were significantly low compared to those isolated from patients with community-associated infection.Compared to pa-tients with community-associated infection,those with health care-associated infection and hospital-associated in-fection had high 28-day case-fatality rates.Thrombocytopenia(HR=1.764,95％CI:1.275-2.440,P=0.001),hypoalbuminemia(HR=2.320,95％CI:1.595-3.374,P＜0.001),coagulation dysfunction(HR=1.605,95％CI:1.141-2.258,P=0.007),procalcitonin＞2.0 ng/ml(HR=3.747,95％CI:1.339-10.485,P=0.012),Charlson comorbidity index ≥5(HR=1.578,95％CI:1.110-2.244,P=0.011)and central ve-nous catheterization(HR=1.848,95％CI:1.322-2.583,P＜0.001)were risk factors for 28-day mortality,while appropriate targeted antibacterial drug therapy(HR=0.399,95％CI:0.291-0.546,P＜0.001)was a protective factor.CONCLUSION Antibacterial drug therapy for patients with health care-associated infection should be guided by their unique pathogens and resistance profiles,and individualized regimens should be devel-oped based on the site and source of infection,regional microbiological characteristics and disease severity to re-duce unnecessary use of antibacterial drug.

OBJECTIVE To compare the clinical and microbiological characteristics of patients with bloodstream in-fection(BSI)and to summarize the risk factors for death in these patients.METHODS Clinical data of 528 patients with BSI admitted to Xijing Hospital,the Fourth Military Medical University from Jul.2018 to Feb.2023 were collected.The clinical characteristics,pathogens,antibacterial drug therapy and 28-day case-fatality rate of the pa-tients with BSI were analyzed.RESULTS Among the 528 patients with BSI,there were 139 patients with commu-nity-associated infection,69 patients with health care-associated infection,and 320 patients with hospital-associat-ed infection.The predominant pathogens isolated from patients with community-associated infection and health care-associated infection were Escherichia coli(53.96％and 42.03％,respectively),while Klebsiella pneumoni-ae was the main pathogen in patients with hospital-associated infection(24.38％),with a wide variety of major pathogens identified.The drug resistance profiles of E.coli and K.pneumoniae isolated from patients with health care-associated infection were similar to those isolated from patients with hospital-associated infection but were significantly low compared to those isolated from patients with community-associated infection.Compared to pa-tients with community-associated infection,those with health care-associated infection and hospital-associated in-fection had high 28-day case-fatality rates.Thrombocytopenia(HR=1.764,95％CI:1.275-2.440,P=0.001),hypoalbuminemia(HR=2.320,95％CI:1.595-3.374,P＜0.001),coagulation dysfunction(HR=1.605,95％CI:1.141-2.258,P=0.007),procalcitonin＞2.0 ng/ml(HR=3.747,95％CI:1.339-10.485,P=0.012),Charlson comorbidity index ≥5(HR=1.578,95％CI:1.110-2.244,P=0.011)and central ve-nous catheterization(HR=1.848,95％CI:1.322-2.583,P＜0.001)were risk factors for 28-day mortality,while appropriate targeted antibacterial drug therapy(HR=0.399,95％CI:0.291-0.546,P＜0.001)was a protective factor.CONCLUSION Antibacterial drug therapy for patients with health care-associated infection should be guided by their unique pathogens and resistance profiles,and individualized regimens should be devel-oped based on the site and source of infection,regional microbiological characteristics and disease severity to re-duce unnecessary use of antibacterial drug.

Objective To study the relationship between the expression of long non-coding RNA lung adenocarcinoma metastasis-associated transcript 1(lncRNA MALAT1)and microRNA(miR)-181a-5p in lung adenocarcinoma tissues and the signal pathway of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3),clinicopathological features and prognosis.Methods 218 patients with lung adenocarcinoma who had surgical resection at our institution between January 2018 and May 2021 had their cancer tissues and nearby normal lung tissues collected,the levels of lncRNA MALAT1,miR-181a-5p and key factors of JAK2/STAT3 signaling pathway(JAK2 mRNA,STAT3 mRNA)in lung adenocarcinoma tissues and adjacent tissues were detected by reverse transcription polymerase chain reaction(RT-PCR).The correlation between the expression levels of lncRNA MALAT1 and miR-181a-5p in cancer tissues of lung adenocarcinoma patients and the levels of key factors in JAK2/STAT3 signaling pathway were analyzed by Pearson test.The relationship between the expression levels of lncRNA MALAT1 and miR-181a-5p and the clinicopathological features of lung adenocarcinoma patients were analyzed.Patients with lung adenocarcinoma were followed up for 3 years,and their prognosis was counted,the 3-year overall survival rate of lncRNA MALAT1 and miR-181a-5p low/high expression groups were analyzed by Kaplan-Meier method.The prognostic factors were analyzed by univariate and multivariate COX risk proportional regression models.Results In lung adenocarcinoma tissues,the expression levels of lncRNA MALAT1,JAK2,and STAT3 mRNA were substantially greater(P＜0.05)than in neighboring normal lung tissues,whereas the expression level of miR-181a-5p was significantly lower(P＜0.05)in compared to nearby normal lung tissues.Pearson test results showed that,lncRNA MALAT1 was positively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=0.526、0.483),and miR-181a-5p was negatively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=-0.430、-0.493).lncRNA MALAT1 had a considerably greater expression rate and miR-181a-5p had a significantly lower expression rate in patients with TNM stage Ⅲa,lymph node metastasis and poorly differentiated lung adenocarcinoma than in patients with TNM stage Ⅰ-Ⅱ,without lymph node metastasis and moderately well differentiated lung adenocarcinoma(P＜0.05).Three patients were lost during the 3-year follow-up of 218 patients with lung adenocarcinoma,and the 3-year overall survival rate was 58.14％(125/215).The 3-year overall survival rate of the lncRNA MALAT1 high expression group was considerably lower than that of the lncRNA MALAT1 low expression group.The miR-181a-5p high expression group had a substantially greater(P＜0.05).Lymph node metastasis,TNM stage Ⅲ a,decreased expression level of miR-181a-5p,and increased expression level of lncRNA MALAT1 are risk factors for the prognosis of patients with lung adenocarcinoma(P＜0.05).Conclusion The low expression of miR-181a-5p and the high expression of lncRNA MALAT1 in lung adenocarcinoma tissues are related to TNM stage Ⅲa,lymph node metastasis and poor prognosis,which may promote the progression of lung adenocarcinoma and cause poor prognosis by activating JAK2/STAT3 signaling pathway.

Objective To study the relationship between the expression of long non-coding RNA lung adenocarcinoma metastasis-associated transcript 1(lncRNA MALAT1)and microRNA(miR)-181a-5p in lung adenocarcinoma tissues and the signal pathway of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3),clinicopathological features and prognosis.Methods 218 patients with lung adenocarcinoma who had surgical resection at our institution between January 2018 and May 2021 had their cancer tissues and nearby normal lung tissues collected,the levels of lncRNA MALAT1,miR-181a-5p and key factors of JAK2/STAT3 signaling pathway(JAK2 mRNA,STAT3 mRNA)in lung adenocarcinoma tissues and adjacent tissues were detected by reverse transcription polymerase chain reaction(RT-PCR).The correlation between the expression levels of lncRNA MALAT1 and miR-181a-5p in cancer tissues of lung adenocarcinoma patients and the levels of key factors in JAK2/STAT3 signaling pathway were analyzed by Pearson test.The relationship between the expression levels of lncRNA MALAT1 and miR-181a-5p and the clinicopathological features of lung adenocarcinoma patients were analyzed.Patients with lung adenocarcinoma were followed up for 3 years,and their prognosis was counted,the 3-year overall survival rate of lncRNA MALAT1 and miR-181a-5p low/high expression groups were analyzed by Kaplan-Meier method.The prognostic factors were analyzed by univariate and multivariate COX risk proportional regression models.Results In lung adenocarcinoma tissues,the expression levels of lncRNA MALAT1,JAK2,and STAT3 mRNA were substantially greater(P＜0.05)than in neighboring normal lung tissues,whereas the expression level of miR-181a-5p was significantly lower(P＜0.05)in compared to nearby normal lung tissues.Pearson test results showed that,lncRNA MALAT1 was positively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=0.526、0.483),and miR-181a-5p was negatively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=-0.430、-0.493).lncRNA MALAT1 had a considerably greater expression rate and miR-181a-5p had a significantly lower expression rate in patients with TNM stage Ⅲa,lymph node metastasis and poorly differentiated lung adenocarcinoma than in patients with TNM stage Ⅰ-Ⅱ,without lymph node metastasis and moderately well differentiated lung adenocarcinoma(P＜0.05).Three patients were lost during the 3-year follow-up of 218 patients with lung adenocarcinoma,and the 3-year overall survival rate was 58.14％(125/215).The 3-year overall survival rate of the lncRNA MALAT1 high expression group was considerably lower than that of the lncRNA MALAT1 low expression group.The miR-181a-5p high expression group had a substantially greater(P＜0.05).Lymph node metastasis,TNM stage Ⅲ a,decreased expression level of miR-181a-5p,and increased expression level of lncRNA MALAT1 are risk factors for the prognosis of patients with lung adenocarcinoma(P＜0.05).Conclusion The low expression of miR-181a-5p and the high expression of lncRNA MALAT1 in lung adenocarcinoma tissues are related to TNM stage Ⅲa,lymph node metastasis and poor prognosis,which may promote the progression of lung adenocarcinoma and cause poor prognosis by activating JAK2/STAT3 signaling pathway.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION chictr.org.cn, ChiCTR 2100043775.
Humans ; Fluorouracil/therapeutic use* ; Leucovorin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Proportional Hazards Models ; Prognosis

Objective:To investigate the influencing of high sodium donor liver transplan-tation from the death of a citizen′s organ donation (DCD) on the prognosis of recipients.Methods:The retrospective cohort study was constructed. The clinicopathological data of 125 pairs of donors and recipients who underwent DCD liver transplantation in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2021 were collected. Of the 125 donors, there were 93 males and 32 females. Of the 125 recipients, there were 92 males and 33 females, aged 48(41,55)years. According to the last time of serum sodium level of donor liver in the 125 recipients, 9 donor livers with serum sodium level ≥170 mmol/L were divided into group 1 (extremely high sodium), 33 donor livers with serum sodium level ≥150 mmol/L and <170 mmol/L were divided into group 2 (moderate high sodium), and 83 donor livers with serum sodium level <150 mmol/L were divided into group 3 (normal sodium), respectively. Observation indicators: (1) postoperative recover situations; (2) follow-up and survival analysis. Measurement data with normal distribution were represented as Mean± SD. Repeated measures were analyzed by repeated measures ANOVA. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Kruskal-Wallis test. Count data were described as absolute numbers, and Pearson chi-square test or Fisher exact probability were used for data test. The Kaplan-Meier method was used to draw survival curves and Log-rank test was used for survival analysis. Results:(1) Postoperative recover situations. The changes of alanine transaminase (AlT), aspartate aminotransferases (AST), total bilirubin (TBil), alkaline phosphatase (ALP), prothrombin time (PT), international normalized ratio (INR), albumin (Alb) and creatinine (Cr) from the first day to the 14th day after operation were (736±972)IU/L to (75±46)IU/L, (1 290±1 651)IU/L to (38±20)IU/L, (102±98)μmol/L to (33±11)μmol/L, (66±34)IU/L to (104±54)IU/L, (19.9±3.3)seconds to (11.3±1.0)seconds, 1.76±0.31 to 1.00±0.08, (34±5)g/L to (38±3)g/L and (91±41)μmol/L to (76±19)μmol/L, respectively, in the recipients of group 1. The above indicators were (505±377)IU/L to (48±46)IU/L, (855±727)IU/L to (24±17)IU/L, (64±42)μmol/L to (32±22)μmol/L, (68±51)IU/L to (91±46)IU/L, (16.8±3.5)seconds to (11.9±1.2)seconds, 1.47±0.30 to 1.04±0.09, (33±4 g/L) to (40±5)g/L and (106±32)μmol/L to (97±27)μmol/L in the recipients of group 2 and (637±525)IU/L to (65±60)IU/L, (929±1 193)IU/L to (33±27)IU/L, (66±48)μmol/L to (33±36)μmol/L, (64±28)IU/L to (125±64)IU/L, (17.2±4.7)seconds to (13.3±12.8)seconds, 1.51±0.42 to 1.05±0.13, (35±6)g/L to (39±4)g/L, (105±44)μmol/L to (94±40)μmol/L in the recipients of groups. Results of overall effect showed there were significant differ-ences in the change trend of TBil (time effect, inter-group effect, interaction effect) in recipients among the three groups after liver transplantation ( Fgroup=5.42, Ftime=22.78, Finteraction=3.85, P<0.05). There were significant differences in the time effect of ALT, AST, ALP, PT, INR, Alb, Cr in recipients among the three groups after liver transplantation ( Ftime=50.17, 36.24, 19.24, 10.55, 59.61, 41.94, 10.82, P<0.05). (2) Follow-up and survival analysis. All recipients were followed up. Cases with early postoperative liver dysfunction, cases with donor liver failure 1 year after operation, cases with biliary complica-tions 1 year after operation, cases with vascular complications 1 year after operation, cases with rejection 1 year after operation were 2, 1, 0, 0, 0 in the recipients of group 1. The above indicators were 2, 1, 3, 0, 1 in the recipients of group 2 and 10, 8,20, 1, 6 in the recipients of group 3. There was no significant difference in the above indicators among the three groups ( χ2=1.58, 0.60, 5.19, 1.62, 0.97, P>0.05). The 1-year and 3-year cumulative survival rates of the donor liver were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 94.74% and 77.16% in the recipients of group 2 and 91.57% and 89.30% in the recipients of group 3. There was no significant difference in the cumulative survival rate of donor liver among the three groups ( χ2=2.69, P>0.05). The 1-year and 3-year cumulative survival rates were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 93.74% and 77.16% in the recipients of group 2 and 89.40% and 86.00% in the recipients of group 3. There was no significant difference in the cumulative survival rate among the three groups ( χ2=1.94, P>0.05). Conclusion:Donor livers with high serum sodium level can be used in the DCD liver transplantation.