Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.

Objective To investigate the feasibility of selectively omitting ureteral stent placement after ureteroscopic lithotripsy(URL).Methods A total of 118 patients with distal ureteral calculi undergoing URL from 2021 to 2024 were enrolled.Patients were divided into a control group(indwelling ureteral stent for 2 weeks,n=86)and an observation group(no ureteral stent placement,n=32).General data,operation time,hospital stay,and total medical costs were compared between the two groups.Patients were followed 2 weeks postoperatively for assessment of flank pain visual analogue scale(VAS)scores,bladder irritation symptoms,hematuria,and incidence of urinary tract infection.Hydronephrosis was evaluated by ultrasonography 3 months after surgery.Results There was no significant difference in the general information and operation time between the two groups(P>0.05).The length of hospital stay and total treatment cost in the observa-tion group were significantly lower than those in the control group(P<0.05).Two weeks after surgery,the VAS scores of low back pain on the affected side and occurrence rates of bladder irritation symptoms,hematu-ria,and urinary tract infection in the observation group were significantly lower than those in the control group(P<0.01).Three months after operation,no hydronephrosis was observed in both groups.Conclusion It is safe and feasible to avoid indwelling ureteral stent after URL in appropriate cases.

Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.

Objective:To investigate the distribution and drug resistance of common pathogens causing urinary tract infection (UTI) in children in Beijing, so as to provide reference for clinical rational use of antibiotics.Methods:It was a retrospective cohort study. The results of clinical data, urine culture and drug sensitivity in children with urinary infection treated in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from June 2018 to June 2018 were retrospectively analyzed. According to the diagnostic criteria of "Chinese expert consensus on the diagnosis and treatment of UTI (2015 edition) - Complicated urinary tract infection", the children were divided into complex group and simple group according to whether they had complicated factors, and the pathogenic factors of the complex group were analyzed. The χ 2 test was used to compare the distribution of pathogenic bacteria in urine culture and the resistance rate of Escherichia coli to common antibiotics between the two groups. Results:A total of 187 children with UTI were enrolled in this study. The age ranged from 1 month after birth to 17 years old, and the median age was 8 months. There were 88 males (47.1%) and 99 females (52.9%), and the male/female ratio was 1:1.125. Male infants accounted for 79.5% (70/88) of male infants and female infants accounted for 48.5% (48/99) of female infants. There were 45 cases (24.1%) in the simple UTI group and 142 cases (75.9%) in the complicated UTI group. A total of 216 strains of pathogens were isolated, mainly Gram-negative bacteria (151/216, 69.9%), of which Escherichia coli was the most common (86/216, 39.8%). The second was gram-positive bacteria (57/216, 26.4%), among which Enterococcus faecium (37/216, 17.1%) was the most common. The positive rate of Escherichia coli infection in the simple UTI group was significantly higher than that in the complicated UTI group [71.1% (32/45) vs. 31.6% (54/171), χ2=23.234, P<0.001], and the positive rate of Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium and fungal infection in the simple UTI group was significantly lower than those in the complicated UTI group. However, the differences were not statistically significant (all P>0.05). The resistance rate of Escherichia coli to ampicillin was the highest in children with UTI [91.9% (79/86)], and it was sensitive to amikacin, meropenem, imipenem, piperacillin/tazobactam, cefepime, piperacillin, cefazolin, cefoperazone/sulbactam. The drug resistance rates were 5.8% (5/86), 5.8% (5/86), 9.3% (8/86), 10.5% (9/86), 14.0% (12/86), 15.1% (13/86), 18.6% (16/86) and 18.6% (16/86), respectively. The resistance rate of Escherichia coli infection to ceftriaxone in the complicated UTI group was significantly higher than that in the simple UTI group [59.3% (32/54) vs. 24.4% (11/32), χ2=4.977, P=0.026]. Eight fungi (3.7%) were susceptible to fluconazole, voriconazole, itraconazole and amphotericin B. Conclusions:The main pathogens of UTI in children are Gram-negative bacteria, among which Escherichia coli is the most common pathogen, but the proportion of infection has a downward trend in recent years. The resistance rate of ceftazidime and ceftriaxone is relatively low, which can be used as empirical drugs for children with UTI in this region.

Objective:To investigate the distribution and drug resistance of common pathogens causing urinary tract infection (UTI) in children in Beijing, so as to provide reference for clinical rational use of antibiotics.Methods:It was a retrospective cohort study. The results of clinical data, urine culture and drug sensitivity in children with urinary infection treated in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from June 2018 to June 2018 were retrospectively analyzed. According to the diagnostic criteria of "Chinese expert consensus on the diagnosis and treatment of UTI (2015 edition) - Complicated urinary tract infection", the children were divided into complex group and simple group according to whether they had complicated factors, and the pathogenic factors of the complex group were analyzed. The χ 2 test was used to compare the distribution of pathogenic bacteria in urine culture and the resistance rate of Escherichia coli to common antibiotics between the two groups. Results:A total of 187 children with UTI were enrolled in this study. The age ranged from 1 month after birth to 17 years old, and the median age was 8 months. There were 88 males (47.1%) and 99 females (52.9%), and the male/female ratio was 1:1.125. Male infants accounted for 79.5% (70/88) of male infants and female infants accounted for 48.5% (48/99) of female infants. There were 45 cases (24.1%) in the simple UTI group and 142 cases (75.9%) in the complicated UTI group. A total of 216 strains of pathogens were isolated, mainly Gram-negative bacteria (151/216, 69.9%), of which Escherichia coli was the most common (86/216, 39.8%). The second was gram-positive bacteria (57/216, 26.4%), among which Enterococcus faecium (37/216, 17.1%) was the most common. The positive rate of Escherichia coli infection in the simple UTI group was significantly higher than that in the complicated UTI group [71.1% (32/45) vs. 31.6% (54/171), χ2=23.234, P<0.001], and the positive rate of Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium and fungal infection in the simple UTI group was significantly lower than those in the complicated UTI group. However, the differences were not statistically significant (all P>0.05). The resistance rate of Escherichia coli to ampicillin was the highest in children with UTI [91.9% (79/86)], and it was sensitive to amikacin, meropenem, imipenem, piperacillin/tazobactam, cefepime, piperacillin, cefazolin, cefoperazone/sulbactam. The drug resistance rates were 5.8% (5/86), 5.8% (5/86), 9.3% (8/86), 10.5% (9/86), 14.0% (12/86), 15.1% (13/86), 18.6% (16/86) and 18.6% (16/86), respectively. The resistance rate of Escherichia coli infection to ceftriaxone in the complicated UTI group was significantly higher than that in the simple UTI group [59.3% (32/54) vs. 24.4% (11/32), χ2=4.977, P=0.026]. Eight fungi (3.7%) were susceptible to fluconazole, voriconazole, itraconazole and amphotericin B. Conclusions:The main pathogens of UTI in children are Gram-negative bacteria, among which Escherichia coli is the most common pathogen, but the proportion of infection has a downward trend in recent years. The resistance rate of ceftazidime and ceftriaxone is relatively low, which can be used as empirical drugs for children with UTI in this region.

Mucosal-associated invariant T (MAIT) cells are highly conserved immune cells that could participate in innate and adaptive immune responses after being activated by major histocompatibility complex class 1-related molecule (MR1) pathway or cytokine pathway. At present, it has been confirmed that a large number of MAIT cells exist in human peripheral blood and specific tissues, and play an important role in infectious diseases. This review focused on the role of MAIT cells in immune responses to different pathogens. Additionally, the therapeutic methods and challenges of targeting MAIT cells in infectious diseases were also discussed.

Objective:By comparing preoperative high resolution magnetic resonance imaging (MRI) examination with postoperative pathologic results, to investigate the effects of MRI examination evaluation on the anatomical level and clinical outcome.Methods:We conducted a retrospective study on 72 patients who underwent resection of rectal cancer at the Second Affiliated Hospital of Wenzhou Medical University between Apr 2017 and Nov 2018, including 35 patients undergoing laparoscopic resection and 37 patients doing open resection. All cases received high resolution MRI examination before operation. The diagnostic accuracy of MRI, operation safety, and the short-term outcomes were analyzed.Results:There were no postoperative tumor recurrence. The accuracy rate of preoperative MRI evaluation of T stage was 85%, and positive N+ was 74%. There were no difference in postoperative complications between the open resection group and laparoscopic resection group (29% vs. 22%, χ 2=0.463, P=0.496). The proximal and distal margin was negative, postoperative circumferential resection margin and preoperative mesorectal fascia was consistent, the distance between the lower margin of the tumor and the anal right angle measured by MRI were consistent with the distance between the tumor from the dentate line. Conclusion:High resolution MRI with a good tissue resolution, has a high preoperative diagnosis accuracy for T and N staging of the low rectal cancer, with decisive role in the evaluation on the anatomical level, improving the quality and safy of surgery.

Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

OBJECTIVETo test the effect of bifunctional molecule IL2-GMCSF in promoting the activation of dendritic cells (DCs) cultured in tumor conditioned medium.

METHODSWe prepared a tumor conditioned medium using mouse melanoma cell line B16F10 supplemented with IL2-GMCSF, GM-CSF, IL-2, or the combination of the latter two. After culturing mouse DC cell line DC2.4 in the conditioned medium for 24 h, the DCs were examined for phagocytosis, proliferation, maturation phenotype, cytokine secretion, and signal pathway activation.

RESULTSDC2.4 cells displayed characteristics of immature DCs. After cell culture in the conditioned medium, the cells showed enhanced phagocytosis but significantly suppressed cell proliferation activity. Culture in the conditioned medium also promoted DC cell maturation and secretion of macrophage-derived chemokine (MDC), but inhibited IL-12 secretion. Supplementation of the conditioned medium with IL2-GMCSF promoted phagocytosis, proliferation, maturation, and cytokine (including both IL-12 and MDC) secretion of DC2.4 cells. Compared with GM-CSF, IL2-GMCSF induced a higher level of NF-κB signal pathway activation but suppressed STAT3 activation.

CONCLUSIONCompared with GM-CSF, IL2-GMCSF can better promote DC activation in the context of tumor-induced immune suppression, and thus shows potentials in anti-tumor therapy.

Animals ; Cell Differentiation ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Chemokine CCL22 ; metabolism ; Culture Media, Conditioned ; chemistry ; Dendritic Cells ; cytology ; drug effects ; Gene Expression Regulation, Neoplastic ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Immune Tolerance ; Interleukin-12 ; metabolism ; Interleukin-2 ; pharmacology ; Melanoma, Experimental ; pathology ; Mice ; NF-kappa B ; metabolism ; Phagocytosis ; STAT3 Transcription Factor ; metabolism ; Signal Transduction

Objective To test the effect of bifunctional molecule IL2-GMCSF in promoting the activation of dendritic cells (DCs) cultured in tumor conditioned medium. Methods We prepared a tumor conditioned medium using mouse melanoma cell line B16F10 supplemented with IL2-GMCSF, GM-CSF, IL-2, or the combination of the latter two. After culturing mouse DC cell line DC2.4 in the conditioned medium for 24 h, the DCs were examined for phagocytosis, proliferation, maturation phenotype, cytokine secretion, and signal pathway activation. Results DC2.4 cells displayed characteristics of immature DCs. After cell culture in the conditioned medium, the cells showed enhanced phagocytosis but significantly suppressed cell proliferation activity. Culture in the conditioned medium also promoted DC cell maturation and secretion of macrophage-derived chemokine (MDC), but inhibited IL-12 secretion. Supplementation of the conditioned medium with IL2-GMCSF promoted phagocytosis, proliferation, maturation, and cytokine (including both IL-12 and MDC) secretion of DC2.4 cells. Compared with GM-CSF, IL2-GMCSF induced a higher level of NF-κB signal pathway activation but suppressed STAT3 activation. Conclusion Compared with GM-CSF, IL2-GMCSF can better promote DC activation in the context of tumor-induced immune suppression, and thus shows potentials in anti-tumor therapy.