Objective To evaluate the efficacy and further analyze the application prospects of the combined multitarget fecal FIT-DNA assay in the early screening of colorectal cancer.Methods Subjects were selected from a population attending the Inner Mongolia Medical University Hospital.Each subject underwent a combined multi-target fecal FIT-DNA test(experimental group),a serum tumor marker test and enteroscopy(control group).The pathological results were used as the gold standard to evaluate the efficacy of novel fecal molecular testing techniques for colorectal cancer screening with timely intervention given to screen positive individuals.Results The data of 115 individuals were analyzed.Serum tumor markers test had a sensitivity of 63.2%(43/68)and a specificity of 74.5%(35/47).The enteroscopy had a sensitivity of 97.1%(66/68)and a specificity of 80.7%(38/47);the combined multitarget fecal FIT-DNA test had a sensitivity of 89.7%(61/68)and a specificity of 87.2%(41/47).Conclusion The sensitivity and specificity of multitarget fecal FIT-DNA combined detection are better than those of serum tumor marker detection.Although its sensitivity is lower than enteroscopy,its operation is simpler and can be tested at home.

Extracellular polymeric substances(EPS)constitutes crucial elements within bacterial biofilms,facili-tating accelerated antimicrobial resistance and conferring defense against the host's immune cells.Developing precise and effective antibiofilm approaches and strategies,tailored to the specific charac-teristics of EPS composition,can offer valuable insights for the creation of novel antimicrobial drugs.This,in turn,holds the potential to mitigate the alarming issue of bacterial drug resistance.Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias,which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds.Considering the pivotal role of EPS in biofilm functionality,it is imperative for EPS research to delve deeper into the analysis of intricate compositions,moving beyond the current focus on polymeric materials.This ne-cessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches.In this study,we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions.Additionally,novel strategies aimed at targeting EPS to enhance biofilm penetration were explored,with a specific focus on high-lighting the limitations associated with colorimetric methods.Furthermore,we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges.This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS,thereby inhibiting biofilm formation.This insight opens up a new avenue for exploration within this research domain.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To evaluate the efficacy of individualized removal therapeutic regimen for donor-specific antibodies (DSA) and examine its related influencing factors.Method:From January 2016 to January 2021, 34 recipients of kidney transplant (KT) underwent regular DSA testing and the results were positive. DSA removal therapy based upon rituximab (RTX) plus intravenous immune globulin (IVIG) was offered. Correlation between DSA negative conversion rate and DSA types, time from start of treatment to transplantation, HLA loci targeted by DSA and DSA mean fluorescent intensity (MFI) were analyzed retrospectively. Changes of immunedominant DSA (iDSA) and serum creatinine in individuals with de novo DSA (dnDSA) before and after treatment were also examined.Results:At Month 3 post-treatment, antibodies turned negative in 17/34(50.0%) patients and DSA became negative in 19/34(55.9%) at the last follow-up. Then we identified 78 DSA from all patients. No significant difference existed in negative conversion rate of pfDSA and dnDSA at Month 3 post-treatment [62.9%(39/62) vs 37.5%(6/16)] and at the last follow-up [4.2%(46/62) vs 56.3%(9/16)]( P=0.067, 0.219). For pfDSA, negative conversion rate of pfDSA with different MFIs after 3-month treatment varied significantly [negative conversion rate of weak positive DSA was 78.6%(33/42) and positive and above DSA 30%(6/20), P<0.001]. It was an independent related factor of whether or not pfDSA could turn negative (48.6%, 95% CI: 22.3%-66.8%, P=0.001). At the last follow-up, negative conversion rate of pfDSA differed markedly at different timepoints from start of treatment to transplantation [treated within 30 days post-operation was 79.2%(42/53) and over 30 days post-operation was 44.4%(4/9), P=0.042] and among different DSA MFI [88.1%(37/42) of weakly positive DSA and 45%(9/20) of positive and above DSA, P<0.001] and they were independent related factors for negative conversion of pfDSA (34.8%, 95% CI: 3.2%-61.8%, P=0.008; 43.1%, 95% CI: 18.5%-63.4%, P=0.001). Mean decline rate in iDSA was 66.67% at Month 3 post-treatment and 77.90% at the last follow-up. The difference was statistically significant ( P=0.035). Serum level of creatinine of 9 patients with dnDSA was (110.2±26.9) μmol/L pre-treatment, (178.8±90.5) μmol/L during treatment, (153.9±72.8) μmol/L at Month 3 post-treatment and (213.6±185.8) μmol/L at the last follow-up. Serum creatinine rose during treatment ( t=-2.794, P=0.023), declined at Month 3 post-treatment ( t=3.430, P=0.009) and spiked again at the last follow-up ( P=0.028). Conclusion:After DSA removal therapy based upon RTX plus IVIG, negative conversion rate of pfDSA is correlated with its MFI and time from start of treatment to transplantation. There is no significant rebound in DSA MFI and graft function of dnDSA patients improves immediately after treatment.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8⁺ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

This review described the management of 11 recipients hospitalized with severe COVID-19 after kidney transplantation during the omicron variant epidemic in Shanghai from December 2022 to January 2023.After withdrawing oral immunosuppressants and starting immunoreplacement therapy, taking small molecule antiviral drugs and treating mixed infections, 10 recipients recovered and were discharged.One critically recipient died from a mixed bacterial and fungal infection after 80-day treatment.No overproduction of inflammatory cytokines was observed during treatment.And no rejection occurred during a cessation of oral immunosuppression.Delayed administration(>1 week of SARS-CoV-2 infection)of small molecule antiviral agents could effectively control viral replication.And there was simultaneous restoration of immune function.

Objective:To explore the risk factors related to acute rejection (AR) after pediatric kidney transplantation (KT).Methods:Retrospective analysis was performed for 189 pediatric KT recipients from September 2011 to August 2022.They were divided into two groups of AR (n=33) and non-AR (n=156).Univariate and multivariate Logistic regression analyses were performed for identifying potential risk factors of AR.And the effects of AR on graft function and survival were also examined.Results:During follow-ups, a total of 33(17.5%) patients developed AR with a 1-year cumulative incidence of AR of 16.9%(32/189).Univariate analysis revealed that median time on dialysis was longer in AR group than that in non-AR group (19 vs. 11 months, P=0.034).Median age of donors (12 vs. 24 months, P=0.033), median weight of donors (9.5 vs. 12 kg, P=0.025) and median donor/recipient body weight ratio (0.36 vs. 0.50, P=0.005) were lower in AR group than those in non-AR group.And the proportion of subtherapeutic tacrolimus (TAC) trough level was higher in AR group than that in non-AR group (45.5% vs. 21.2%, P=0.004).Multivariate regression analysis indicated that subtherapeutic TAC trough level was an independent risk factor for AR ( OR=2.977, 95% CI: 1.314-6.743, P=0.009).At the last follow-up, serum creatinine and eGFR were (78.4±24.3) vs. (74.6±24.7) μmol/L and (85.3±26.3) vs. (89.5±24.2) ml·min -1·1.73 m -2 in AR and non-AR groups respectively.There were no significant differences.1/5-year patient survival rate was both 97% in AR group and both 99.4% in non-AR group; 1/5-year graft survival rate both 90.9% in AR group and was 98.1% and 97.4% in non-AR group.No significant inter-group differences existed in patient and graft survival. Conclusions:Although an occurrence of early AR does not negatively impact graft outcomes, the incidence of AR remains high after pediatric KT.Therefore prompt diagnosis and treatment of AR should be strengthened.

Objective:To investigate the influence of liver drainage volume on overall survival time in patients with unresectable malignant hilar bile duct obstruction.Methods:Data of 633 patients with unresectable malignant hilar bile duct obstruction (BismuthⅡ-Ⅳ) who underwent endoscopic stent drainage in 3 endoscopy centers from January 2002 to May 2019 were retrospectively analyzed. Main observation indicators included clinical success rate, stent patency, overall survival, the effective liver drainage volume, and complication incidence.Results:The clinical success rates of patients with liver drainage volume <30%, 30%-50%, and >50% were 56.8% (25/44), 77.3% (201/260) and 84.2% (277/329) respectively. The incidences of early cholangitis were 31.8% (14/44), 18.8% (49/260) and 16.1% (53/329). The median stent patency time was 4.5 (95% CI: 1.8-7.2) months, 5.6 (95% CI: 5.0-6.2) months and 6.6 (95% CI: 5.2-8.0) months. The overall survival time was 2.4 (95% CI: 1.8-3.0) months, 4.0 (95% CI: 3.4-4.6) months and 4.9 (95% CI:4.4-5.4) months, respectively. The clinical success rate ( χ 2=8.28, P=0.012), median stent patency period ( χ 2=18.87, P=0.015) and overall survival time ( χ 2=6.93, P=0.024) of 30%-50% liver drainage volume group were significantly higher than those of <30% group. Further multivariate cox regression analysis showed that the disease type (hepatocellular carcinoma VS hilar cholangiocarcinoma: HR=1.50, 95% CI:1.18-1.91, P=0.001; gallbladder carcinoma VS hilar cholangiocarcinoma: HR=1.45, 95% CI:1.14-1.85, P=0.002; metastatic cholangiocarcinoma VS hilar cholangiocarcinoma: HR=1.48, 95% CI:1.08-2.04, P=0.015), bilirubin level >200 μmol/L ( HR=1.35, 95% CI:1.14-1.60, P<0.001),metal stents ( HR=0.67, 95% CI:0.56-0.79, P<0.001), liver drainage volume (volume 30%-50% VS <30%: HR=0.64, 95% CI: 0.45-0.90, P=0.010; volume>50% VS <30%: HR=0.58, 95% CI:0.41-0.81, P=0.002) and anti-tumor therapy ( HR=0.51, 95% CI:0.42-0.61, P<0.001) were independent predictors for overall survival time of patients with unresectable malignant hilar bile duct obstruction. Conclusion:When endoscopic stent drainage is performed for patients with unresectable malignant hilar bile duct obstruction, at least 30% liver volume is required for better overall survival. In addition, the use of metal stent drainage and anti-tumor therapy may increase survival benefits.

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

Objective:To investigate the application value of different metal stents place-ment position in endoscopic drainage of malignant hilar bile duct obstruction.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 300 patients with malignant hilar bile duct obstruction who were admitted to 3 medical centers, including 216 patients in the Third Affiliated Hospital of Naval Medical University, 48 patients in the Xijing Hospital of Air Force Medical University, 36 patients in the First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, from January 2012 to January 2019 were collected. There were 164 males and 136 females, aged (67±12)years. All patients were determined to be unresectable by multidisciplinary consultation and underwent endoscopic retrograde cholangiopancreatography. Observation indicators: (1) clinicopathological features of patients; (2) follow-up; (3) analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients. Follow-up was conducted using outpatient examination and telephone interview to detect patency of metal biliary stents and survival of patients up to July 2019 or death of patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used to conduct survival analysis. COX regression model was used for univariate and multivariate analyses. Factors with P<0.1 in univariate analysis were included in multivariate analysis. Results:(1) Clinicopathological features of patients. Of the 300 patients, 163 cases underwent endoscopic drainage with at least one metal biliary stent' distal portion crossing the duodenal main papilla (hereinafter referred to as crossing papilla), and 137 cases underwent endoscopic drainage with no metal biliary stent' distal portion crossing the duodenal main papilla (hereinafter referred to as no crossing papilla). Age, disease type (hilar cholangiocarcinoma, hepatocellular carcinoma, intrahepatic cholangio-carcinoma, gallbladder carcinoma, metastatic cholangiocarcinoma), metal biliary stents type (unilateral metal biliary stent, bilateral metal biliary stents) of patients with crossing papilla were (68±13)years, 95, 8, 11, 31, 18, 63, 100, respectively. The above indicators of patients with no crossing papilla were (64±12)years, 63, 22, 20, 23, 9, 126, 11, respectively. There were significant differences in the above indicators between patients with crossing papilla and patients with no crossing papilla ( t=2.70, χ2=17.69, 90.79, P<0.05). (2) Follow-up. All the 300 patients were followed up for 5.4(3.1,9.3)months. The patency time of metal biliary stents was 9.0(8.2,9.8)months and 6.4(4.8,8.0)months of patients with crossing papilla and patients with no crossing papilla, showing a significant difference between them ( χ2=8.23, P<0.05). The overall survival time was 5.5(4.2,6.8)months and 5.5(4.3,6.8)months of patients with crossing papilla and patients with no crossing papilla, showing no significant difference between them ( χ2=0.28, P>0.05). (3) Analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients. Results of univariate analysis showed that type of metal biliary stents and the placement position of metal biliary stents were related factors affecting the patency time of metal biliary stents [ hazard ratio( HR)=0.44, 0.60, 95% confidence intervals as 0.30?0.64, 0.42?0.85, P<0.05]. Results of multi-variate analysis showed that bilateral metal biliary stents was an independent protective factor for the patency time of metal biliary stents ( HR=0.46, 95% confidence interval as 0.29?0.72, P<0.05). Results of univariate analysis showed that disease type (intrahepatic cholangiocarcinoma versus hilar cholangiocarcinoma), preoperative serum total bilirubin, type of metal biliary stents, anti-tumor therapy were related factors affecting the overall survival time of patients ( HR=1.05, 1.43, 0.72, 0.61, 95% confidence intervals as 0.70?1.57, 1.12?1.83, 0.55?0.92, 0.47?0.81, P<0.05). Results of multi-variate analysis showed that age >60 years, disease type as hepatocellular carcinoma, preoperative serum total bilirubin >200 μmol/L were independent risk factors for the overall survival time of patients ( HR=1.35, 1.98, 1.46, 95% confidence intervals as 1.02?1.79, 1.40?2.80, 1.13?1.89, P<0.05), and bilateral metal biliary stents, anti-tumor therapy were independent protective factors for the overall survival time of patients ( HR=0.68, 0.60, 95% confidence intervals as 0.53?0.89, 0.45?0.80, P<0.05). Conclusions:Endoscopic drainage with or without metal biliary stents' distal portion crossing the duodenal main papilla is safe and feasible for patients with malignant hilar bile duct obstruction. Bilateral metal biliary stents is an independent protective factor for the patency time of metal biliary stents. Age >60 years, disease type as hepatocellular carcinoma, preoperative serum total bilirubin >200 μmol/L are independent risk factors for the overall survival time of patients, and bilateral metal biliary stents, anti-tumor therapy are independent protective factors for the overall survival time of patients.