AIM:To explore the mechanisms behind the inhibition of lymphangiogenesis in pregnant rats with obstructive nephropathy and assess the protective effects on kidney function.METHODS:Forty nulliparous female Wi-star rats were randomly assigned to four groups:sham operation,sham operation+pregnancy,model,and Esaxerenone groups,with 10 rats in each group.Renal injury was induced in the model and Esaxerenone groups via unilateral ureteral obstruction(UUO).The other two groups underwent ureteral dissociation without ligation.Nine weeks post-UUO,female rats in the sham operation+pregnancy,model,and Esaxerenone groups were mated with male rats(2:1 ratio)to establish a rat model of obstructive nephropathy during pregnancy.Starting the day after UUO,rats in the Esaxerenone group re-ceived Esaxerenone at 1 mg·kg-1·d-1.On the 18th day of pregnancy,24-hour urine was collected using metabolic cages.The following day,the rats were sacrificed,serum samples collected,and the contralateral kidney removed.Blood urea ni-trogen(BUN)was measured using standard biochemical methods,and endogenous creatinine clearance rate(Ccr)was calculated.Kidney tissue pathology was assessed using HE,Masson,and Sirius red staining.Serum aldosterone levels were determined via ELISA.Immunohistochemistry,real-time PCR,and Western blot were employed to assess mineralo-corticoid receptor(MR)activation,lymphangiogenesis,signaling pathways,and fibrosis-related markers.RESULTS:Renal function tests revealed increased BUN levels and decreased Ccr in the model group(P<0.01).Pathological exami-nation showed dilated renal tubules,significant collagen deposition,and inflammatory cell infiltration in the model group.ELISA results indicated a significant increase in serum aldosterone levels in the model group(P<0.01).Immunohisto-chemistry showed enhanced nuclear translocation of MR in the kidneys of the model group post-activation.Western blot and real-time PCR demonstrated a marked increase in neutrophil gelatinase-associated lipocalin(NGAL)expression in the model group(P<0.01).Additionally,the expression of vascular endothelial growth factor C(VEGF-C)and its receptor VEGFR3 was significantly elevated in the renal tubulointerstitium of the model group,as shown by both immunohistochem-istry and real-time PCR(P<0.01).The PI3K/Akt signaling pathway was activated in the model group,with significantly increased phosphorylation levels observed primarily in renal tubular epithelial and interstitial cells(P<0.01).Collagen type III(Col III)expression,primarily in the renal tubulointerstitium,was also significantly upregulated in the model group,consistent with real-time PCR results(P<0.01).Esaxerenone treatment improved renal function,reduced patho-logical damage,inhibited aldosterone secretion,and downregulated the expression of MR,NGAL,VEGF-C,VEGFR3,phosphorylated PI3K,phosphorylated Akt,and Col III(P<0.01).CONCLUSION:Esaxerenone mitigates aldosterone-induced MR activation,modulates the PI3K/Akt signaling pathway,reduces lymphangiogenesis in the contralateral kidney of pregnant rats with obstructive nephropathy,decreases collagen deposition,and delays the progression of renal intersti-tial fibrosis.

OBJECTIVE: We aimed to understand the willingness and barriers to the acceptance of tuberculosis (TB) preventive treatment (TPT) among people with latent TB infection (LTBI) in China. METHODS: A multicenter cross-sectional study was conducted from May 18, 2023 to December 31, 2023 across 10 counties in China. According to a national technical guide, we included healthcare workers, students, teachers, and others occupations aged 15-65 years as our research participants. RESULTS: Overall, 17.0% (183/1,077) of participants accepted TPT. There were statistically significant differences in the acceptance rate of TPT among different sexes, ages, educational levels, and occupations ( P < 0.05). The main barriers to TPT acceptance were misconceptions that it had uncertain effects on prevention (57.8%, 517/894), and concerns about side effects (32.7%, 292/894). CONCLUSION An enhanced and comprehensive understanding of LTBI and TPT among people with LTBI is vital to further expand TPT in China. Moreover, targeted policies need to be developed to address barriers faced by different groups of people.
Humans ; China/epidemiology* ; Adult ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Young Adult ; Adolescent ; Aged ; Latent Tuberculosis/prevention & control* ; Patient Acceptance of Health Care ; Tuberculosis/prevention & control* ; Antitubercular Agents/therapeutic use* ; Health Knowledge, Attitudes, Practice

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective To investigate the effects of T. gondii soluble tachyzoite antigen (STAgs) on the survival time of mouse heart allograft and the possible mechanism. Methods The STAgs were prepared by pulverizing T. gondii tachyzoite with ultrasound on ice. Cervical heterotopic heart transplantations were done by using Balb/c mice as donors, and C57BL/6 mice as recipients.The recipients were classified randomly into three groups: syngeneic group, acute rejection group and STAgs-treated group. The recipients in acute rejection group and STAgs-treated group were injected subcutaneously with 0. 1 ml PBS and 0. 1 ml (5 μg) STAgs at the 4th day before transplantation respectively, and those in syngeneic group were not subjected to any treatment. The grafts were observed daily by cervical palpation, and the total cessation of cardiac contraction was defined as the endpoint. The heart allografts were harvested at the 7th day after transplantation for pathological examination and immunohistochemical staining for CD4+ T, CD8+ T. Results The recipients in syngeneic group were all alive at the 100th day after transplantation. The average survival time in acute rejection group and STAgs-treated group was (6.7± 0.5) days and (70.8± 3.5) days,respectively (P＜0.05). HE staining showed that the rejection on the 7th day after transplantation in syngeneic group, acute rejection group and STAgs-treated group was fallen into 0 degree, Ⅲ-Ⅳ degree and 0- Ⅰ degree, respectively. Immunohistochemical staining revealed that the CD4+ T and CD8+T were markedly down-regulated in STAgs-treated group as compared with those in acute rejection group. Conclusion T. gondii STAgs can significantly prolong the survival time of mouse heart allograft and inhibit the rejection probably by changing the ratio of TH1/TH2, or inhibiting the effect of dendritic cells by inducing the lipoxin A4.

Objective To explore the expression level of Tim-3,the marker of activated T_H 1 cells.in T lymphocytes in different sites from recipients with acute rejection.Methods The model of cervical heterotopic heart transplantation was established in mice Two groups were get up:the isograft group(C57BL/6→C57BL/6) and the allograft group (Balb/c→C57BL/6).Lymphocytes were isolated from peripheral blood,spleens,draining lymph nodes and grafts 3 or 6 days after transplantation.The expression of TIM-3 in CD4~+ and CD8~+ T subsets was detected by flow cytometry.Results There was no significant difference in Tim-3~+/CD4~+ and Tim-3~+/CD8~+ ratio in peripheral blood or spleens between two groups.As compared with the isograft group,the proportion of Tirn-3~+/CD4~+ cells was slightly elevated in draining lymph node(P<0.05),but the percentage of Tim-3~+/CD4~+ cells had no significant change between 3 days and 6 days in the allograft group(P>0.05).The expression of Tim-3 in CD4~+ and CD8~+ of graft infiltrating T cells was obviously increased in allograft group(P<0.01),and it was significantly (P<0.01) up-regulated on the 6th day as compared with that on the 3rd day.Conclusion The dynamic changes of Tim-3 expression in T lymphocytes in draining lymph node and graft were correlated with the progresston oi acute rejection in mice.

To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis (2-D DIGE) and reversed phase high-performance liquid chromatog-raphy (RP-HPLC) followed by electrospray ionization mass spectrometry (ESI-MS) were used. Serum samples from renal allograft patients and normal volunteers were divided into three groups: acute rejec-tion (AR), stable renal function (SRF) and normal volunteer (N). Serum samples were firstly processed using Multiple Affinity Removal Column to selectively remove the highest abundance proteins. Differ-entially expressed proteins were analyzed using 2-D DIGE. These differential protein spots were ex-cised, digested by trypsin, and identified by RP-HPLC-ESI/MS. Twenty-two differentially expressed proteins were identified in serum from AR group. These proteins included complement C9 precursor,apolipoprotein A-Ⅳ precursor, vitamin D-binding protein precursor, beta-2-glycoprotein 1 precursor,etc. Vitamin D-binding protein, one of these proteins, was confirmed by ELISA in the independent set of serum samples. In conclusion, the differentially expressed proteins as serum biomarker candidates may provide the basis of acute rejection noninvasive diagnosis. Confirmed vitamin D-binding protein may be one of serum biomarkers of acute rejection. Furthermore, it may provide great insights into un-derstanding the mechanisms and potential treatment strategy of acute rejection.

To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis (2-D DIGE) and reversed phase high-performance liquid chromatography (RP-HPLC) followed by electrospray ionization mass spectrometry (ESI-MS) were used. Serum samples from renal allograft patients and normal volunteers were divided into three groups: acute rejection (AR), stable renal function (SRF) and normal volunteer (N). Serum samples were firstly processed using Multiple Affinity Removal Column to selectively remove the highest abundance proteins. Differentially expressed proteins were analyzed using 2-D DIGE. These differential protein spots were excised, digested by trypsin, and identified by RP-HPLC-ESI/MS. Twenty-two differentially expressed proteins were identified in serum from AR group. These proteins included complement C9 precursor, apolipoprotein A-IV precursor, vitamin D-binding protein precursor, beta-2-glycoprotein 1 precursor, etc. Vitamin D-binding protein, one of these proteins, was confirmed by ELISA in the independent set of serum samples. In conclusion, the differentially expressed proteins as serum biomarker candidates may provide the basis of acute rejection noninvasive diagnosis. Confirmed vitamin D-binding protein may be one of serum biomarkers of acute rejection. Furthermore, it may provide great insights into understanding the mechanisms and potential treatment strategy of acute rejection.