Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

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.

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

ObjectiveThis study aimed to develop a novel method for encapsulating oocytes in sodium alginate hydrogel using microfluidics, then to vitrify these encapsulated oocytes in a single-step process with low concentrations of cryoprotectants. MethodsWe utilized a flow-focusing microfluidic chip to generate sodium alginate hydrogel microspheres. The influence of various parameters, including throat structure, cross-linking method, sodium alginate concentrations, and flow rate ratios on the stability diameter, and coefficient of variation of microspheres were examined. To further investigate the cold-resistance of these microspheres, we used cryomicroscopy to observe changes in volume and morphology of microspheres during cooling and warming processes. We used microfluidic chip to encapsulate oocytes in sodium alginate hydrogel microspheres, the empty rate of microspheres and loss rate of oocytes were determined. After releasing from microspheres and parthenogenetic activation with cytochalasin B and strontium chloride, the survival, cleavage and blastocyst rates were evaluated during in vitro maturation. Finally, oocytes encapsulated in sodium alginate microspheres were vitrified with low concentrations of cryoprotectants. We compared the survival and development capability of the oocytes with the Cryotop method. ResultsWhen the throat of the microfluidic chip measures 300 μm in length and 120 μm in width, microspheres can be uniformly formed at the throat of the chip. Sodium alginate generates microspheres with a wide size distribution when cross-linking outside the chip, while internal cross-linking within the chip results in more uniform microspheres. The stability of microsphere formation is significantly improved with the use of a three-channel internal cross-linking chip. At a flow rate of 2 μl/min and with 1% sodium alginate, the microfluidic chip can consistently and uniformly produce microspheres. Under flow rate ratios of 10, 15, and 20, the average microsphere diameters are 262.71 μm, 193.63 μm, and 156.63 μm, respectively. The sodium alginate hydrogel microspheres maintained their volume and structural integrity during the cooling and warming processes. Using a three-channel internal cross-linking microfluidic chip to encapsulate oocytes, at a flow rate ratio of 10, the empty rate is 32.28%, and the cell loss rate is 11.09%. After encapsulation and subsequent release, the oocyte survival rate (96.99%), cleavage rate (88.71%), and blastocyst formation rate (26.29%) showed no significant differences compared to the fresh group. After the microspheres were vitrified using a low concentration of cryoprotectant (10% DMSO+10% ehylene glycol (EG)+0.5 mol/L trehalose), the survival rate, cleavage rate, and blastocyst rate were 92.48%, 70.80%, and 20.42%, respectively. No significant difference was observed when compared to the Cryotop method using a higher concentration of cryoprotectant solution (15% DMSO+15% EG+0.5 mol/L trehalose). ConclusionWe designed and fabricated a microfluidic system with three-channel internal cross-linking chips used for oocyte vitrification preservation. The microfluidic system can generate oocytes-loaded sodium alginate hydrogel microspheres with uniform size, low empty rate, and good cold-resistance. The method successfully reduced the concentration of cryoprotectants in a single-step vitrification process, the developmental capability of oocytes during in vitro maturation were comparable with Cryotop method. Unlike the Cryotop method, the oocytes encapsulated in hydrogel does not come into contact with liquid nitrogen, eliminating the risk of cross-contamination. This study provides a novel approach to oocyte vitrification.

ObjectiveTePixD (Tll0078) is a blue light-using flavin (BLUF) photoreceptor protein from Thermosynechococcus elongatus BP-1. TePixD protein has a conserved Tyr8-Gln50-Met93 triad around the FAD pocket to mediate the proton-coupled electron transfer (PCET) process. But the detailed light response mechanism needs further study. We aimed to elucidate the structure and biochemical properties of TePixD mutants at key light response sites to analyze the light response process of TePixD. MethodsWe employed X-ray crystallography to resolve the crystal structure of the TePixD Y8F mutant. The side chain of Tyr8 is involved in PCET while Phe8 in mutation loses the function due to the loss of its hydroxyl group. We compared the structure of TePixD Y8F mutation to TePixD wild type (WT) and its homology protein SyPixD Y8F. Using multi-angle light scattering (MALS), we analyzed the oligomerization of multiple TePixD mutations (Y8F, Q50L, W91F, Y8F/W91F, and Q50L/W91F), focusing specifically on mutational sites that are critical residues for the protein’s photo response to dark and light conditions. ResultsWe resolved the crystal structure of TePixD Y8F mutant at a resolution of 2.54 Å and found that it shares a similar overall structure with the TePixD WT but exhibits significant differences from the SyPixD Y8F structure. Biochemical analysis revealed differences in molecular mass and elution profiles between the TePixD mutants and the WT under dark and light conditions, indicating the perturbation on the light-induced conformational change by the mutants. ConclusionOur structure determination and biochemical analyses will add information to reveal the light response mechanism of BLUF proteins.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective To investigate the effects of pulsed radiofrequency(PRF)with intercostal nerve block on analgesia analgesia effect,cognitive function and postoperative delirium in elderly patients undergoing thoracoscopic lung surgery.Methods Ninety elderly patients undergoing thoracoscopic lung surgery in our hospital were randomly divided into the control group(intercostal nerve block with local anesthetic drugs)and the PRF group(PRF with intercostal nerve block).The pain score,analgesic effect,cognitive function,postoperative delirium and neurological dysfunction of the two groups were compared.Results The pain scores of resting and coughing state 48 hours and 72 hours after surgery in the PRF group were significantly lower than those in the control group(P<0.05).The number of analgesic pump compression and proportion of supplemental analgesia within 72 hours after surgery and perioperative sufentanil dosage in the PRF group were significantly less than those in the control group(P<0.05).The cognitive function scores 48 hours and 72 hours after surgery in the PRF group were significantly higher than those in the control group(P<0.05).The incidence of delirium 72 hours after surgery in the PRF group was significantly lower than that in the control group(P<0.05).There was no significant difference in the incidence of intercostal nerve dysfunction 1 month,2 months and 3 months after surgery between the two groups(P>0.05).Conclusion PRF with intercostal nerve block can effectively relieve pain after elderly thoracoscopic lung surgery,reduce postoperative opioid consumption,improve postoperative cognitive function,and decrease postoperative delirium incidence without affecting the intercostal nerve function,which is safe and reliable.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.