Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.

Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.

AIM:To evaluate the effectiveness of heparin-binding protein(HBP)in combination with organ function indicators for early diagnosis and prognosis prediction in patients with severe trauma complicated with sepsis.METHODS:A retrospective analysis was conducted on 184 patients with multiple injuries who were admitted to the Emergency Medicine Department of the Second Affiliated Hospital of Zhejiang University Medical College between January 2019 and September 2020 and underwent HBP testing.Patients were classified according to the SEPSIS 3.0 diagnostic cri-teria into a sepsis group(n=89)and a non-sepsis group(n=95).Clinical outcomes were tracked,dividing patients into a deceased group(n=43)and a survival group(n=141).HBP levels were continuously measured,and the peak values of the two groups were compared to assess the efficacy of diagnosing sepsis.Further analysis on the correlation of HBP peak value median with clinical prognosis was conducted.The effectiveness of HBP alone and in combination with total biliru-bin(TBil)and white blood cell(WBC)count in prognosis assessment was evaluated.RESULTS:(1)No significant dif-ference was found in the peak level of HBP between the sepsis group(n=89)and the non-sepsis group(n=95)(71.7±68.6 vs 52.5±56.1,P=0.051).(2)Among the 184 patients,the peak level of HBP was positively correlated with WBC count(r=0.244,P<0.01)and TBil levels(r=0.241,P<0.01).(3)The area under curve(AUC)for independent diag-nosis of sepsis using TBil levels,WBC count,and PCT levels were 0.618,0.631,and 0.718,respectively,and the com-bined AUC was 0.684,with a diagnostic sensitivity of 60.7%and specificity of 71.6%(P<0.05).(4)Prognostic analy-sis of mortality showed that patients in the high HBP level group had a significantly higher mortality rate than those in the low-level group(30.4%vs 16.3%,P<0.05).The WBC count was also significantly higher in the deceased group than in the survival group(17.5±6.9 vs 12.8±4.7,P<0.01),especially in those with sepsis(P<0.01).The AUCs for predict-ing sepsis mortality prognosis using HBP peak level,TBil levels,WBC count,SOFA score,and APACHE-II score were 0.618,0.603,0.719,0.823,and 0.811,respectively.The combined AUC of HBP with TBil and WBC for assessing sepsis prognosis was 0.750,with a sensitivity of 74.4%and specificity of 74.5%,showing statistically significant differ-ences(P<0.05).(5)The combined assessment of these three indicators showed no statistically significant difference from artificial scoring systems in predicting sepsis prognosis(P>0.05).CONCLUSION:The combination of HBP,TBil,and WBC is highly effective in predicting the risk of sepsis in patients with multiple injuries and has significant clinical value in predicting the mortality risk of trauma patients with sepsis.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective:To study the influence of intensive magnet fields on radiation dose measurement, and to demonstrate the feasibility of measuring magnet field correction factor by a combination of medical linac with variable magnet fields in view of needing for accurate measurement of the doses from reference beam arising in MR image-guided radiotherapy.Methods:A photon radiation field and a variable field with 6 MV nominal high voltage were produced by using conventional medical electron linear accelerator equipped with a pair of electromagnets with magnetic field strength up to 1.5 T. Both PTW30013 and PTW31010 ionization chambers were used to test the responses of ionization chambers under different magnetic field strengths at four orientations in which the angles between ionization chamber axis and magnetic field direction were 0°, 180°, 90° and 270°, respectively. The magnetic factors, kB, M was calculated and compared with the reported values in literature. Results:The response of ionization chamber was proportional to the magnetic field strength before it reached to a peak around 1 T, and then fell down as the magnetic field continued to rise. When the magnetic field was 0.35 T, the magnetic factors of PTW31010 were 0.988 2±0.000 3 and 0.997 4±0.000 4 corresponding to 90° and 0° directions, the discrepancy between 0° scenario and literature was 0.05% ± 0.04%. When the magnetic field reached 1.5 T, the magnetic factor of PTW30013 was 0.958 9±0.000 5 at the situation of 90°, which was 0.60% ± 0.05% different from the literature value.Conclusions:Conventional 6 MV medical accelerator equipped with electromagnet can be used to measure the magnetic field factor of reference dosimetry for MRIgRT.

The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-‍κB (NF-‍κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1β (IL-‍‍1β), tumor necrosis factor-α (TNF‍-‍α), and interferon-‍γ (IFN-‍γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.
Cytokines/genetics* ; Humans ; Inflammatory Bowel Diseases ; NF-kappa B/metabolism* ; Protein Processing, Post-Translational ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To investigate the clinical effect of early arthroscopic shoulder treatment of moderate full-thickness tear of the supraspinatus tendon.Methods:A retrospective case control study was conducted to analyze the clinical data of 43 patients with moderate full-thickness supraspinatus tendon tear admitted to First Affiliated Hospital of Xi 'an Jiaotong University from January 2018 to June 2020，including 17 males and 26 females，aged from 41 to 68 years［（55.9±8.2）years］. All patients had arthroscopic shoulder supraspinatus tendon suture and acromioplasty，including 22 patients underwent surgery within 1 month after persistent shoulder pain and motion limitation in early group and 21 patients between 1 month and 3 months in late group. The duration of operation and intraoperative blood loss were recorded. The visual analogue scale（VAS），American Shoulder and Elbow Society（ASES）score and Constant-Murley score were assessed before operation and at postoperative 3 weeks，6 weeks，3 months and 6 months. The complications were detected with 6 months after operation. Results:All patients were followed up for 6-7 months［（6.4±0.4）months］. There was no statistical significance in operation duration and intraoperative blood loss between the two groups（ P>0.05）. At 3 weeks，6 weeks，3 months and 6 months after operation，there showed significant decrease of VAS but significant increase of ASES and Constant-Murley scores compared to preoperation（ P<0.05）. At 3 weeks and 6 weeks after operation，the VAS in early group［（4.4±0.9）points，（3.7±0.8）points］was lower than that in late group［（5.5±1.0）points，（4.8±1.1）points］；while the ASES score［（49.1±4.6）points，（56.8±4.1）points］and Constant-Murley score［（54.1±4.8）points，（64.1±4.4）points］in early group were higher than those in late group［ASES score：（45.2±5.4）points，（50.3±5.4）points；Constant-Murley score：（50.5±3.3）points，（58.2±3.9）points］（ P<0.05）. At 3 months and 6 months after operation，the two groups showed no statistical significance in these scores. There were no postoperative complications such as infection or nerve injury in both group within 6 months. Conclusion:For moderate full-thickness tear of the supraspinatus tendon，arthroscopic shoulder surgery performed within 1 month after persistent shoulder pain and motion limitation can achieve better pain relief and faster functional rehabilitation in the short term compared with surgery performed 1-3 months later.

Objective To compare the efficacy and safety of the long-term intermittent maintenance treatment with tacrolimus 0.03％ ointment versus traditional treatment in reducing relapses and prolonging the recurrence interval in children with moderate to severe atopic dermatitis (AD).Methods A two-phase randomized,open-labelled,controlled clinical trial was conducted from September 2012 to November 2013.In the first phase,a total of 171 children aged 2-15 years with moderate to severe AD were enrolled from 7 hospitals in China,and received conventional treatment with tacrolimus 0.03％ ointment twice a day for 2-6 weeks.At the end of the treatment,the patients who achieved an investigator's global assessment (IGA) score ≤ 2 (n =125) were randomly classified into 2 groups to receive the second-phase treatment:test group (n =62) receiving intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week (Monday and Thursday),and control group (n =63) receiving no treatment.If the patients in the 2 groups experienced relapse,they received conventional treatment with tacrolimus 0.03％ ointment twice a day.The overall observation period was 6 months.The primary endpoint was the time to the first relapse,which was defined as the number of days from the end of the first-phase treatment to the first relapse.The secondary endpoints included the number of relapses at the second-phase trial,the disease severity at the time of relapse,the duration of relapse,the pruritus score at the time of relapse,the total amount of tacrolimus ointment used,the total response rate at the second-phase trial,and the incidence of adverse events.Results A total of 125 children with AD were enrolled into the second-phase trial,and 121 of them completed the follow-up.Among the 121 patients,the recurrence rate was significantly lower in the test group (25/60,41.7％) than in the control group (46/61,75.4％;x2 =14.20,P ＜ 0.001).The time to the first relapse was significantly longer in the test group (46.9 ± 37.7 d) than in the control group (28.8 ± 32.3 d;Z =1 093.50,P =0.020).The total number of recurrence was 31 and 86 in the test group and control group respectively,and the mean number of recurrence in each patient was significantly lower in the test group (0.52 ± 0.68) than in the control group (1.41 ± 1.23,t =4.96,P ＜ 0.001).There were no significant differences between the two groups regarding disease severity during relapse (eczema area and severity index:Z =971.50,P =0.39),duration of relapse (Z =747.00,P =0.07),and pruritus score during relapse (Z =894.00,P =0.95).The therapeutic drug was tolerated well in all the children,and no tacrolimus-related serious adverse events occurred.Conclusion The intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week for 6 months can effectively and safely prevent and reduce relapses,and prolong the recurrence interval in children with moderate to severe AD.

Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid plaque pathogenesis in Alzheimer's disease (AD). Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB (TFEB), an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ (fAβ) degradation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APP/PS1 transgenic mice. Our findings reveal that deacetylation of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
Alzheimer Disease ; metabolism ; pathology ; Amyloid beta-Peptides ; metabolism ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; chemistry ; genetics ; metabolism ; Brain ; metabolism ; Cells, Cultured ; Chloride Channels ; genetics ; metabolism ; Disease Models, Animal ; HEK293 Cells ; Humans ; Lysosomes ; genetics ; metabolism ; Mice ; Mice, Transgenic ; Microglia ; cytology ; metabolism ; Mutagenesis, Site-Directed ; Peptides ; analysis ; chemistry ; Protein Binding ; RNA Interference ; Sirtuin 1 ; antagonists & inhibitors ; genetics ; metabolism

Objective:To predict and analyze the secondary structure and B cell epitopes of Izumo protein.Methods: The secondary structure and flexible regions of Izumo protein were predicted by the methods of Chou-Fasman,Gamier-Robson and Karplus-Schulz.Moreover,hydrophilicity plot,surface probability plot and antigenic index of Izumo protein were predicted by the methods of Kyte-Doolitde,Emini and Jameson-Wolf,respectively.Results: Izumo protein contained moreαhelix regions.There were several centers ofαhelix in the regions of 6-17,30-40,88-99,103-120,153-160,173-188,249-260,283-297,334-338 and 339-346 of Izumo protein,and several centers of βsheet in the regions of 21-25,198-200,245-248 and 320-323.Moreover,many distinct B cell epitopes in Izumo protein possibly localized in the regions of 3642,62-66,94-99,118-122,129-132,151-154,161-164,173-177,205-208,212-216,256-265,271-276,283-288,314-318 and 336-350.Conclusion:These results are helpful for identification of the dominant B cell epitopes and the functional domains of Izumo protein.