Objective To investigate the acceptance and satisfaction of tuberculosis prevention and control personnel in Beijing with the patient management system, and to provide a basis for further improving the patient management model. Methods A survey was conducted on the current usage, satisfaction, willingness to use and system improvement opinions of the patient management system among medical staff involved in the supervision and medication management of pulmonary tuberculosis patients in Beijing. Results A total of 360 medical staff participated in the survey. ^“Patient management^” was the function with the largest number of users, accounting for 96.94%. The proportion of users of each module who believed that the module's design met actual work needs was over 90%. About 94.44% of respondents believed that patient management systems facilitated the transfer and sharing of information between institutions. And 90.83% of respondents thought that the patient management system was easy to operate, and 89.17% of respondents believed that patient management systems reduced workload. About 97.50% of respondents were satisfied with the overall use of the patient management system. The results of the influencing factor analysis showed that those with 3 or less modules designed to meet actual work were less satisfied than those with more than 3 modules, and the difference was statistically significant (P=0.001). Respondents put forward suggestions for improvement on the optimization of operational details such as system response speed, interface design, system login and query statistics. Conclusion Medical staff involved in the follow-up management of pulmonary tuberculosis patients are highly satisfied with their work using the patient management system. During the promotion and use, it is still necessary to continuously optimize the system functions according to work needs so that the system can truly facilitate work.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF).Methods:220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ2 test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results:There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group ( P ?

Objective To observe the value of extracellular volume(ECV)and relative electron density(RED)based on dual-layer detector spectral CT(DLCT)for identifying colon cancer invasion into serous membrane.Methods Sixty-two patients with pathologically confirmed colon cancer with blurred pericolonic fat gap on CT images were retrospectively collected,including 18 cases of T4a stage tumors with serous membrane invasion and 44 cases of T2-T3 stage without serous membrane invasion.The arterial,venous and delayed phase DLCT images under 40 keV showing the largest diameter of colon cancers were analyzed.The iodine concentration(IC)and RED of the pericolonic fat around tumor-bearing and tumor-free intestines,as well as of the abdominal aorta or the common or external iliac artery were measured,while normalized IC(NIC)and difference of RED(REDdiff)of pericolonic fat around tumor-bearing and tumor-free intestines in each phase and ECV in delayed phase were calculated.The above parameters were compared between tumors with different stages,and for those with significant differences,the receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated to evaluate and compare the efficacies for identifying invasion of serous membrane in T4a stage colon cancer.Results Compared with T2-T3 stage colon cancers,T4a stage colon cancers were found more often occurred in patients aged ＜50 with higher proportion of lymph node metastases(both P＜0.05),also higher values of NIC and REDdiff on images in different phases,as well as ECV in delayed phase images(all P＜0.05).The AUC of arterial,venous and delayed phase NIC for differentiating T2-T3 and T4a stage colon cancers ranged from 0.868 to 0.902,while of REDdiff ranged from 0.848 to 0.903,all without significant difference(all P＞0.05).The AUC of delayed phase ECV was 0.948,not significant different with that of delayed phase NIC and REDdiff,arterial phase NIC nor venous phase REDdiff(all P＞0.05).Conclusion Based on DLCT,ECV and RED could be used to identifying serous membrane invasion of colon cancer when blurred pericolonic fat gaps were noticed.

Purpose To observe the clinical and CT features of severe immune checkpoint inhibitor-related pneumonitis(CIP)in lung cancer patients.Materials and Methods A total of 174 patients with lung cancer who received immune checkpoint inhibitor(PD-1/PD-L1 inhibitors)in Xi'an International Medical Center Hospital from September 1,2019 to March 31,2022 were retrospectively collected.Clinical and imaging features of patients with severe CIP were analyzed.Results There were 23 patients who met the diagnostic criteria of severe CIP.Among them,22 were male patients,15 were younger(＜65 years old),17 had a history of underlying lung disease,16 had a history of chemoradiotherapy and other treatments,and 21 had a history of combined radiotherapy and chemoradiotherapy.The median time from the initiation of immune checkpoint inhibitor to CIP was 128(74,348)days.19 patients were non-small cell carcinoma.CIP occurred in 16 patients with right lung cancer,15 had tumor central airway invasion,14 had radiographic features of diffuse alveolar injury/acute interstitial pneumonia pattern,and 20 died during follow-up.Conclusion Severe CIP is likely to occur in male lung cancer patients with a history of basic medical history and radiotherapy and chemotherapy.The clinical manifestations are varied,and the main imaging features are diffuse alveolar injury/acute interstitial pneumonia pattern,and the prognosis is poor.

Objective:To explore the strategy of prostate biopsy in patients with prostate specific antigen(PSA)gray zone based on prostate imaging reporting and data system (PI-RADS).Methods:The clinical data of 427 patients who underwent transperineal prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. The median age was 66 (61, 72) years old. The median PSA was 6.62 (5.46, 8.19) ng/ml. The median PSA density (PSAD) was 0.15 (0.11, 0.21) ng/ml 2. The median prostate volume (PV) was 43.68 (31.12, 56.82) ml. PSA velocity (PSAV) data were available in 65 patients with negative MRI examination(PI-RADS <3), and the median PSAV was 1.40 (0.69, 2.89) ng/(ml· year). Among the patients with positive MRI(PI-RADS≥3), there were 174 patients with only 1 lesion and 83 patients with ≥2 lesions. A total of 170 patients with negative MRI underwent systematic biopsy, and 257 patients with positive MRI underwent systematic combined targeted biopsy. The PI-RADS score, regions of interest(ROI), PSAD, f/tPSA and PSAV were analyzed to explore the biopsy strategy for patients with PSA gray area based on bpMRI imaging. Results:Of the 427 patients included in the study, 194 were positive and 233 were negative. Among the patients with positive biopsy pathology, 140 cases were clinically significant prostate cancer (CsPCa). Among the MRI-negative patients, there were 33 cases with PSAV ≥1.4 ng/(ml·year), and 10 cases of prostate cancer and 6 cases of CsPCa were detected by systematic biopsy.In 32 cases with PSAV <1.4 ng/(ml·year), 3 cases of prostate cancer and 0 case of CsPCa were detected by systematic biopsy. The sensitivity of systematic biopsy for the diagnosis of prostate cancer and CsPCa in patients with PSAV≥1.4 ng/(ml·year) were 76.9% (10/13) and 100.0% (6/6) respectively, the specificity were 55.8% (29/52) and 54.2% (32/59) respectively, the negative predictive value were 90.6% (29/32) and 100.0% (32/32) respectively, and the positive predictive value were 30.3% (10/33) and 18.2% (6/33) respectively. In MRI-positive patients with PI-RADS 3, the prostate cancer detection rates of targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 41.7% (45/108), 32.4% (35/108) and 35.2% (38/108), respectively ( P=0.349). The detection rates of CsPCa were 27.8% (30/108), 21.3% (23/108) and 25.0% (27/108), respectively ( P=0.541). In patients with PI-RADS 4-5 and PSAD > 0.15 ng/ml 2, the detection rates of CsPCa in targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 67.8% (61/90), 58.9% (53/90) and 67.8% (61/90), respectively ( P=0.354). Conclusions:For MRI-negative patients, all CsPCa could be detected by perineal systematic biopsy when PSAV ≥1.4 ng/(ml·year), and active observation could be performed when PSAV <1.4 ng/(ml·year). For MRI-positive patients, targeted combined systemic biopsy was required when PI-RADS score was 3, and targeted biopsy only could be performed when PI-RADS score ≥4 and PSAD >0.15 ng/ml 2, otherwise targeted combined systemic biopsy was required.

Objective:To investigate the effect of astragaloside Ⅳ on the apoptosis of thyroid cells in Hashimoto's thyroiditis(HT)rats and Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil containing kinase 2(ROCK2)pathway.Methods:The HT rat model was induced by subcutaneous injection of thyroglobulin combined with high iodine drinking water and randomly divided into model group,astragaloside(80 mg/kg)group,Rhosin(RhoA inhibitor,40 mg/kg)group,astragaloside Ⅳ(80 mg/kg)+ Rhosin(40 mg/kg)group(12 rats in each group),another 12 SD rats were selected and drank water normally and injected the same dose of saline subcutaneously as control group.After the drugs were grouped and processed,the serum anti-thyroglobulin antibody(TGAb),anti-thyroid peroxidase antibody(TPOAb)levels and the inflammatory factors IL-6,IL-17,IL-1β contents were measured by ELISA kits;the pathological changes of thyroid tissue in each group were detected by hematoxylin-eosin(HE)staining;the apopto-sis rate of rat thyroid cells in each group were detected by TUNEL staining;the expressions of RhoA/ROCK2 pathway proteins in thy-roid tissues of rats in each group were detected by Western blot.Results:Compared with the control group,the thyroid follicles in the model group had abnormal structure,some atrophy or disappearance,disordered arrangement,surrounding inflammatory cell infiltra-tion,and obvious pathological damage to the thyroid tissue,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were significantly increased(P<0.05);compared with model group,the pathological damage of the thyroid tissue of rats in the drug intervention group were reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05);compared with astragaloside Ⅳ group and the Rhosin group respectively,the pathological damage of the thyroid tissue of rats in the astragaloside Ⅳ+Rhosin group were further reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05).Conclusion:Astragaloside Ⅳ may down-regulate the expression of RhoA/ROCK2 pathway to reduce the inflammatory injury of thyroid tissue,inhib-it thyroid cell apoptosis,and improve the symptoms of HT in rats.

Objective:To study the incidence and risk factors of central vein stenosis (CVS) in chronic kidney disease (CKD) patients who received arteriovenous fistula (AVF) creation for the first time, as well as effects of CVS on patency of ipsilateral AVF.Methods:It was a retrospective study. The CKD patients who received AVF creation for the first time in the First Affiliated Hospital of Zhengzhou University from January 2019 to August 2020, with central vein digital subtraction angiography (DSA) results prior to angioplasty were selected as the study subjects. The differences of incidence of CVS in CKD patients with/without a history of cervical catheterization and primary patency rates of AVF between CVS and non-CVS groups were compared. Logistic regression analysis method was applied to analyze the influencing factors of CVS in CKD patients. Kaplan-Meier method was used to analyze the primary patency rate of AVF. Cox regression analysis method was used to analyze the effect of CVS on the primary patency of ipsilateral AVF.Results:A total of 283 CKD patients aged (50.45±14.76) years were enrolled in the study, including 165 males (58.3%). The dialysis age was 0.5 (0, 7.0) months. There were 55 patients (19.4%) diagnosed with CVS before AVF, including 39 patients with stenosis <50% and 16 patients with stenosis ≥50%. The incidence of CVS in patients with history of right internal jugular vein central venous catheter insertion was significantly higher than that in those without this history [60.5% (26/43) vs. 9.9% (15/151), χ2=51.274, P<0.001]. Multivariate logistic regression analysis results showed that hemodialysis catheters indwelling time ≥3 months elevated the risk of CVS ( OR=4.345, 95% CI 1.540-12.263, P=0.006). A subset of 268 patients who had AVF creation ipsilateral to CVS were analyzed to determine the effects of CVS on patency of AVF. The median follow-up time was 34 months. The primary patency rate of AVF in the moderate to severe CVS group was significantly lower than that in the non-CVS group (5/7 vs. 58/228, χ2=7.720, P=0.005). The primary patency rates of AVF in the subclavian vein stenosis group and superior vena cava stenosis group were significantly lower than those in the brachiocephalic vein stenosis group (4/5 vs. 8/27, χ 2=6.974, P=0.008; 6/8 vs. 8/27, χ 2=6.908, P=0.009, respectively). Moderate to severe CVS and combined diabetes were independent influencing factors of primary patency of AVF ( HR=4.362, 95% CI 1.644-11.574, P=0.003; HR=2.682, 95% CI 1.624-4.431, P<0.001, respectively). Conclusions:The incidence of CVS is higher in CKD patients who establish an arteriovenous fistula for the first time. Hemodialysis catheter indwelling time ≥3 months is an independent risk factor of CVS. The moderate to severe CVS is an independent risk factor of primary patency of AVF.

In order to achieve large-scale production of HSV-IgM (HSV1, HSV2) human-mouse chimeric antibody in vitro, the gene sequence of the corresponding hybridoma cell was harvested by RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) technique to clone the chimeric antibody into eukaryotic expression vectors, and express the target proteins in CHO-S cells. At the same time, the screening process of stable cell lines was optimized, and the pressure conditions of pool construction stage and monoclonal screening stage were explored. Finally, the target protein was purified by protein L affinity purification method and the biological activity was detected. The recombinant IgM antibodies, HSV1 and HSV2, weighted at 899 kDa and 909 kDa respectively, were prepared. The optimal screening pressure was 20P200M (the first phase of pressure) and 50P1000M (the second phase of pressure). The final titer for the monoclonal expression of HSV1-IgM and HSV2-IgM was 1 620 mg/L and 623 mg/L, respectively. This study may facilitate the development of quality control products of HSV1 and HSV2 IgM series recombinant antibodies as well as efficient expression of IgM subtype antibodies in vitro.
Cricetinae ; Humans ; Animals ; Mice ; Immunoglobulin M/genetics* ; Antibodies, Viral ; CHO Cells ; Cricetulus ; Hybridomas ; Recombinant Fusion Proteins

ObjectiveTo investigate the influencing factors for the prognosis of patients with acute－on－chronic liver failure （ACLF）， and to establish a short－term prognostic model. MethodsA retrospective analysis was performed for the baseline clinical data of 247 patients with ACLF who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Xi’an Jiaotong University， from January 2011 to December 2016， and the patients were divided into survival group and death group. The two groups were compared to identify the influencing factors for prognosis； a prognostic model was established， and the receiver operating characteristic （ROC） curve was used to assess its predictive efficacy and determine the optimal cut－off value. The independent－samples t test was used for comparison of normally distributed continuous data between groups， and the Mann－Whitney U rank sum test was used for comparison of non－normally distributed continuous data between groups； the Fisher’s exact test or the Pearson’s chi－square test was used for comparison of categorical data between groups. The univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for 28－ and 90－day prognosis， and the Kaplan－Meier method was used to plot the 28－day survival curves. ResultsA total of 220 patients with ACLF were included based on the inclusion and exclusion criteria； there were 148 patients in the 28－day survival group and 72 patients in the 28－day death group， with a 28－day transplantation－free survival rate of 67.27%； there were 115 patients in the 90－day survival group and 105 patients in the 90－day death group， with a 90－day transplantation－free survival rate of 52.27%. The logistic regression analysis showed that female sex （odds ratio ［OR］=2.149， P=0.030）， high Model for End－Stage Liver Disease （MELD） score （OR=1.120， P<0.001）， and low lymphocyte count （OR=0.411， P=0.002） were independent risk factors for 28－day prognosis， and an LS－MELD model for 28－day prognosis was established as Logit （28－day prognosis）=－3.432+0.765×sex－0.890×lymphocyte count×10^－9+0.113×MELD（1 for male sex and 2 for female sex）. The ROC curve analysis showed that this model had an optimal cut－off value of 0.35， and then the patients were divided into low LS－MELD group （≤0.35） and high LS－MELD group （>0.35）； the low LS－MELD group had a significantly higher 28－day survival rate than the high LS－MELD group （P<0.001）. ConclusionPeripheral blood lymphocyte count combined with sex and MELD score has a certain value in predicting the short－term prognosis of ALCF patients.