Objective:To investigate the correlation between serum growth differentiation factor 15 (GDF15) and the clinicopathological characteristics of patients with IgA nephropathy (IgAN), and further explore the relationship of GDF15 with the cardiac and renal prognosis of IgAN patients.Methods:It was a single-center retrospective cohort study. From January 2018 to December 2022, the relevant data were collected from patients who were diagnosed with primary IgAN at the Department of Nephrology, Beijing Anzhen Hospital Affiliated to Capital Medical University, and regularly followed up for at least 1 year. Serum samples were collected at admission and the baseline level of serum GDF15 was measured. Based on the median GDF15 level, IgAN patients were categorized into high-level GDF15 group and low-level GDF15 group, and their clinicopathological characteristics were compared. A multiple linear regression model was then constructed to identify independent factors associated with serum GDF15 level based on these comparisons. Subsequently, Kaplan-Meier survival analysis was performed to investigate the association between serum GDF15 level and the cardiorenal prognosis of IgAN patients.Results:A total of 104 IgAN patients were included in this study. The serum GDF15 level in these IgAN patients was 825.60 (556.84, 1 428.15) ng/L. Serum GDF15 level was positively correlated with 24 h urinary protein ( r=0.405, P<0.001), negatively correlated with estimated glomerular filtration rate (eGFR)( r=-0.606, P<0.001). The serum levels of GDF15 in patients with tubular atrophy or interstitial fibrosis (overall comparison among T0, T1, and T2, H=21.866, P<0.001), crescentic lesions (overall comparison among C0, C1, and C2, H=13.787, P=0.001), or intrarenal arteriolar lesions (overall comparison among none, mild, and moderate-to-severe, H=9.856, P=0.007) were significantly different. Compared with IgAN patients without tubular atrophy or interstitial fibrosis, those with Oxford classification T1 ( Z=-17.326, P=0.042) or T2 ( Z=-42.933, P<0.001) had higher serum GDF15 levels. Compared with IgAN patients without crescentic lesions, those with Oxford classification C2 had higher serum GDF15 levels ( Z=-45.929, P=0.001). Compared with IgAN patients without intrarenal arteriolar lesions, those with moderate-to-severe arteriolar sclerosis had higher serum GDF15 levels ( Z=-26.686, P=0.005). The median GDF15 was used as the cut-off value to divide IgAN patients into a high-level GDF15 group (≥825.60 ng/L, n=52) and a low-level GDF15 group (<825.60 ng/L, n=52). Compared to low-level GDF15 group, IgAN patients in high-level GDF15 group presented with a higher proportion of diabetes mellitus ( χ 2=9.420, P=0.002) and cardiovascular disease ( χ 2=7.792, P=0.005), a higher level of systolic blood pressure ( Z=-2.266, P=0.023), body mass index ( Z=-2.183, P=0.031), 24 h urinary protein ( Z=-3.485, P<0.001), blood total cholesterol ( Z=-2.002, P=0.045) and left ventricular mass index ( Z=-2.649, P=0.008), and a lower level of blood albumin ( Z=-3.053, P=0.002) and eGFR ( Z=6.480, P<0.001). Multiple linear regression analysis showed that serum GDF15 level was independently associated with systolic blood pressure (regression coefficient B=29.453, 95% CI 14.139–44.767, P<0.001), blood albumin ( B=-81.412, 95% CI -113.084–-49.740, P<0.001) and eGFR ( B=-9.797, 95% CI -17.554–-2.040, P=0.014). Moreover, IgAN patients in high-level GDF15 group exhibited significantly poorer cardiac and renal prognosis compared to low-level GDF15 group ( χ 2=9.955, P=0.002). Conclusion:High serum GDF15 level correlates with disease severity in IgAN, and high serum GDF15 level may suggest a poorer cardiorenal prognosis in IgAN patients.

Objective: To compare the efficacy of heat and acid elution methods for IgG anti-M and anti-Ku. Methods: Ten samples with IgG anti-M and two samples with IgG anti-Ku were selected and standardized to a titer of 64. These antibodies underwent overnight absorption at 4℃ with O-type MM and kk-type erythrocytes, and then heat and acid elution methods were used on the absorbed sensitized erythrocytes respectively by detecting the titer of anti-M and anti-Ku in the eluate to compare the differences in the elution efficiency of IgG anti-M and anti-Ku between the two elution methods. Results: In heat elution tests, all 10 anti-M samples showed positive results with titers ranging from 8 to 64, while 2 anti-Ku samples yielded negative results. In acid elution tests, all 10 anti-M samples demonstrated negative results, whereas both anti-Ku (n=2) samples exhibited positive reactions with consistent titers of 32. Following acid elution with subsequent heat elution, 8 of 10 anti-M samples showed positive results with titers ranging from 8 to 32, while 2 remained negative. Both anti-Ku samples demonstrated positive with titers of 4. Conclusion: Heat elution demonstrated superior efficiency for IgG anti-M compared to acid elution, whereas acid elution showed greater efficacy for IgG anti-Ku than heat elution.

Objective: To compare the efficacy of heat and acid elution methods for IgG anti-M and anti-Ku. Methods: Ten samples with IgG anti-M and two samples with IgG anti-Ku were selected and standardized to a titer of 64. These antibodies underwent overnight absorption at 4℃ with O-type MM and kk-type erythrocytes, and then heat and acid elution methods were used on the absorbed sensitized erythrocytes respectively by detecting the titer of anti-M and anti-Ku in the eluate to compare the differences in the elution efficiency of IgG anti-M and anti-Ku between the two elution methods. Results: In heat elution tests, all 10 anti-M samples showed positive results with titers ranging from 8 to 64, while 2 anti-Ku samples yielded negative results. In acid elution tests, all 10 anti-M samples demonstrated negative results, whereas both anti-Ku (n=2) samples exhibited positive reactions with consistent titers of 32. Following acid elution with subsequent heat elution, 8 of 10 anti-M samples showed positive results with titers ranging from 8 to 32, while 2 remained negative. Both anti-Ku samples demonstrated positive with titers of 4. Conclusion: Heat elution demonstrated superior efficiency for IgG anti-M compared to acid elution, whereas acid elution showed greater efficacy for IgG anti-Ku than heat elution.

Objective To analyze the dynamic changes and influencing factors of Mycobacterium tuberculosis(TB)infection in grade-1 students in senior high school at the time of enrollment and one year after enrollment.Methods In 2022,TB screening was carried out among grade-2 students in 4 senior high schools in Binhai and Xiqing Districts of Tianjin.Basic information of students was collected,and TB infection detection results of grade-1 students in senior high school at the time of enrollment were collected retrospectively.Positive rate,strong positive rate and positive conversion rate from tuberculin skin test(TST)results of students were compared.Univariate and multiva-riate logistic regression models were used to analyze the relevant influencing factors for positive conversion of TST results.Results The overall positive rate of 1 839 students one year after enrollment was higher than that at the enrollment(46.82％vs 33.12％),while strong positive rate was lower(12.51％vs 13.00％),both with statisti-cally significant differences(both P＜0.001).One year after enrollment,64 out of 1 230 students who were origi-nally negative for TST in their first year of senior high school turned positive,with a positive conversion rate of 5.20％(95％CI:3.93％-6.48％).One year after enrollment,TST results showed that the average diameter of induration was 5(2,8)mm,diameter was 2(0,5)mm at the enrollment of the first year of senior high school,but the difference was not statistically significant(P=0.478).The difference range of average diameter of induration was±21 mm,39.70％of students being within±2 mm.Students with increased and decreased average diameter of induration accounted for 65.09％and 28.49％,respectively.Multivariate logistic regression analysis result showed that students in boarding school had a higher risk of positive conversion compared with non-boarding school students(OR=4.842,95％CI:2.794-8.392).Conclusion The screening of TB infection among grade-2 students in senior high school should be strengthened,with a focus on boarding school students.Early detection of tuberculosis patients and newly infected individuals can provide reference for implementing precise prevention and control.

Objective To analyze the dynamic changes and influencing factors of Mycobacterium tuberculosis(TB)infection in grade-1 students in senior high school at the time of enrollment and one year after enrollment.Methods In 2022,TB screening was carried out among grade-2 students in 4 senior high schools in Binhai and Xiqing Districts of Tianjin.Basic information of students was collected,and TB infection detection results of grade-1 students in senior high school at the time of enrollment were collected retrospectively.Positive rate,strong positive rate and positive conversion rate from tuberculin skin test(TST)results of students were compared.Univariate and multiva-riate logistic regression models were used to analyze the relevant influencing factors for positive conversion of TST results.Results The overall positive rate of 1 839 students one year after enrollment was higher than that at the enrollment(46.82％vs 33.12％),while strong positive rate was lower(12.51％vs 13.00％),both with statisti-cally significant differences(both P＜0.001).One year after enrollment,64 out of 1 230 students who were origi-nally negative for TST in their first year of senior high school turned positive,with a positive conversion rate of 5.20％(95％CI:3.93％-6.48％).One year after enrollment,TST results showed that the average diameter of induration was 5(2,8)mm,diameter was 2(0,5)mm at the enrollment of the first year of senior high school,but the difference was not statistically significant(P=0.478).The difference range of average diameter of induration was±21 mm,39.70％of students being within±2 mm.Students with increased and decreased average diameter of induration accounted for 65.09％and 28.49％,respectively.Multivariate logistic regression analysis result showed that students in boarding school had a higher risk of positive conversion compared with non-boarding school students(OR=4.842,95％CI:2.794-8.392).Conclusion The screening of TB infection among grade-2 students in senior high school should be strengthened,with a focus on boarding school students.Early detection of tuberculosis patients and newly infected individuals can provide reference for implementing precise prevention and control.

Objective:To investigate the correlation between serum growth differentiation factor 15 (GDF15) and the clinicopathological characteristics of patients with IgA nephropathy (IgAN), and further explore the relationship of GDF15 with the cardiac and renal prognosis of IgAN patients.Methods:It was a single-center retrospective cohort study. From January 2018 to December 2022, the relevant data were collected from patients who were diagnosed with primary IgAN at the Department of Nephrology, Beijing Anzhen Hospital Affiliated to Capital Medical University, and regularly followed up for at least 1 year. Serum samples were collected at admission and the baseline level of serum GDF15 was measured. Based on the median GDF15 level, IgAN patients were categorized into high-level GDF15 group and low-level GDF15 group, and their clinicopathological characteristics were compared. A multiple linear regression model was then constructed to identify independent factors associated with serum GDF15 level based on these comparisons. Subsequently, Kaplan-Meier survival analysis was performed to investigate the association between serum GDF15 level and the cardiorenal prognosis of IgAN patients.Results:A total of 104 IgAN patients were included in this study. The serum GDF15 level in these IgAN patients was 825.60 (556.84, 1 428.15) ng/L. Serum GDF15 level was positively correlated with 24 h urinary protein ( r=0.405, P<0.001), negatively correlated with estimated glomerular filtration rate (eGFR)( r=-0.606, P<0.001). The serum levels of GDF15 in patients with tubular atrophy or interstitial fibrosis (overall comparison among T0, T1, and T2, H=21.866, P<0.001), crescentic lesions (overall comparison among C0, C1, and C2, H=13.787, P=0.001), or intrarenal arteriolar lesions (overall comparison among none, mild, and moderate-to-severe, H=9.856, P=0.007) were significantly different. Compared with IgAN patients without tubular atrophy or interstitial fibrosis, those with Oxford classification T1 ( Z=-17.326, P=0.042) or T2 ( Z=-42.933, P<0.001) had higher serum GDF15 levels. Compared with IgAN patients without crescentic lesions, those with Oxford classification C2 had higher serum GDF15 levels ( Z=-45.929, P=0.001). Compared with IgAN patients without intrarenal arteriolar lesions, those with moderate-to-severe arteriolar sclerosis had higher serum GDF15 levels ( Z=-26.686, P=0.005). The median GDF15 was used as the cut-off value to divide IgAN patients into a high-level GDF15 group (≥825.60 ng/L, n=52) and a low-level GDF15 group (<825.60 ng/L, n=52). Compared to low-level GDF15 group, IgAN patients in high-level GDF15 group presented with a higher proportion of diabetes mellitus ( χ 2=9.420, P=0.002) and cardiovascular disease ( χ 2=7.792, P=0.005), a higher level of systolic blood pressure ( Z=-2.266, P=0.023), body mass index ( Z=-2.183, P=0.031), 24 h urinary protein ( Z=-3.485, P<0.001), blood total cholesterol ( Z=-2.002, P=0.045) and left ventricular mass index ( Z=-2.649, P=0.008), and a lower level of blood albumin ( Z=-3.053, P=0.002) and eGFR ( Z=6.480, P<0.001). Multiple linear regression analysis showed that serum GDF15 level was independently associated with systolic blood pressure (regression coefficient B=29.453, 95% CI 14.139–44.767, P<0.001), blood albumin ( B=-81.412, 95% CI -113.084–-49.740, P<0.001) and eGFR ( B=-9.797, 95% CI -17.554–-2.040, P=0.014). Moreover, IgAN patients in high-level GDF15 group exhibited significantly poorer cardiac and renal prognosis compared to low-level GDF15 group ( χ 2=9.955, P=0.002). Conclusion:High serum GDF15 level correlates with disease severity in IgAN, and high serum GDF15 level may suggest a poorer cardiorenal prognosis in IgAN patients.

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

OBJECTIVE To monitor the occurrence of tenofovir disoproxil fumarate （TDF）-induced kidney injury and investigate the risk factors， and provide reference for rational use of TDF in clinic. METHODS The information of inpatients with hepatitis B was collected by China Hospital Pharmacovigilance System （CHPS） from the Second People’s Hospital of Lanzhou during Jan. 1st， 2019 to Dec. 31st 2021. The search criteria were set according to kidney injury criteria， and suspected TDF- induced kidney injury cases were actively monitored； then the clinical pharmacist confirmed the positive patients with TDF-induced kidney injury one by one and calculated the incidence of TDF-induced renal injury； the risk factors for TDF-induced kidney injury in real world were explored by collecting and analyzing the correlation of basic data of patients， main indexes of liver and kidney function， complications and combined use of drugs with TDF-induced renal indexes. RESULTS Totally 1 226 inpatients with hepatitis B using TDF were included. Through active monitoring of CHPS， 160 suspected patients with TDF-induced kidney injury were found， and 64 positive patients were finally confirmed manually. The incidence of TDF-induced kidney injury was 5.22%. Compared with pre-medication， the levels of serum creatinine and cystatin C， the proportion of patients with urinary protein 2+ and above were increased significantly after medication （P＜0.001）， glomerular filtration rate and blood phosphorus level were reduced significantly （P＜0.001） and other indicators had no statistical difference. Treatment time for more than 36 months， disease progresses to decompensated cirrhosis， and concomitant use of more than 10 kinds of drugs were significantly correlated with TDF- related kidney injury （P＜0.05 or P＜0.012 5）. CONCLUSIONS The active monitoring scheme of TDF-induced kidney injury established by CHPS has the characteristics of time-saving， labor-saving and high efficiency； based on real-world evidence， it is imperative to strengthen monitoring kidney function of patients when using TDF， especially when the patient has been on medication for a long time， in decompensated cirrhosis and combination of multiple drugs， and thus， we can identify earlier and avoid adverse effects in high-risk patientseffectively.

Background: Previous study has found that ursolic acid (UA) inhibited the proliferation of gastric cancer cells by the down-regulation of cyclooxygenase-2 (COX-2) expression.However,its molecular mechanism is not fully clear.Aims: To investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/signal transducer and activator of transcription 3 (STAT3)/COX-2 signaling pathway in UA-mediated inhibition of gastric cancer cells proliferation.Methods: AMPK-pLVX,AMPK-shRNA,STAT3-pLVX,STAT3-shRNA plasmids were constructed,and then were transfected into human gastric cancer cell lines SGC-7901 and MKN-45,respectively.Gastric cancer cells were cultured with different concentrations of UA for different times.The expressions of phosphorylated AMPK (p-AMPK),phosphorylated STAT3 (p-STAT3) and COX-2 were measured by Western blotting,and cell proliferation was detected by CCK-8 assay.Results: UA dose-and time-dependently increased p-AMPK expression,inhibited p-STAT3 and COX-2 expressions in SGC-7901 and MKN-45 cells.Knockdown of AMPK blocked UA-induced inhibition of STAT3 phosphorylation and COX-2 expression.Overexpression of STAT3 blocked UA-induced down-regulation of COX-2 expression.Knockdown of AMPK and overexpression of STAT3 blocked UA-induced inhibition of proliferation of gastric cancer cells.Conclusions: UA may inhibit the proliferation of gastric cancer cells via down-regulation of COX-2 expression through AMPK/STAT3 pathway.

Objective To investigate the value of T2WI histogram analysis in differential diagnosis of glioblastoma multiform (GBM) from solitary metastasis.Methods Data of 103 patients with pathologically confirmed GBM (GBM group,n=57) and solitary brain metastasis (solitary brain metastasis group,n =46) were retrospectively reviewed.All patients underwent conventional MR scanning,including axial T1WI,T2WI,FLAIR and contrast-enhanced T1WI before surgery.The histogram metrics,including mean,standard deviation (SD),median,kurtosis and skewness were calculated from ROI,which were manually placed on the maximal section of the solid part of tumors on T2WI by using Image J software.ROCs were generated to evaluate differential diagnostic performance of the histogram metrics with significant difference between both groups.Results The values of mean,SD and median were significantly higher in GMB group than those in solitary brain metastasis group (P＜0.05).The areas under ROC curve of mean,SD and median was 0.772 (95％ CI [0.681,0.862],P＜0.001),0.719 (95％ CI [0.616,0.822],P＜0.001) and 0.767 (95％ CI [0.674,0.860],P＜0.001),respectively;and the diagnosis cutoff value of mean,SD and median was 509.575,58.844 and 550.500,respectively.The sensitivity of the three parameters was 0.719,0.702 and 0.719,and the specificity was 0.783,0.652,and 0.826,respectively.Conclusion The value of mean,SD and median of T2WI histogram analysis can be helpful to differentiating GBM and solitary brain metastasis,of which the mean value is the best for differential diagnosis.