Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective To systematically retrieve,evaluate and integrate the best evidences on the early fluid resuscitation management in the patients with acute pancreatitis(AP)at home and abroad to provide ref-erence for clinical decision.Methods The related evidences on the early fluid resuscitation management in the AP patients were retrieved by computer from the databases of BMJ Best Practice,Up To Date,JBI,National Institute for Health and Care Excellence,Registered Nurses Association of Ontario,Guideline International Network,Scottish Intercollegiate Guidelines Network,International Association of Pancreatology,American Pancreatic Association,American College of Gastroenterology,Yimaitong,Cochrane Library,PubMed,Em-bass,CINAHL,The Web of Science,CNKI,Wanfang databases.The retrieval time limit was from the data-base establishment to March 20,2022.The literatures types included thematic evidence summarization,guide-lines,evidence summaries,systematic reviews and expert consensus.The researchers conducted the literature quality evaluation.The literatures meeting the standard conducted the evidence extraction.Results A total of 13 arti-cles were included,including 3 special subject evidence summary,4 guidelines,2 evidence summary,2 systematic evalu-ation and 2 expert consensus.A total of 16 pieces of best evidence were integrated,involving 4 aspects of organization management,evaluation and monitoring,fluid infusion strategy and health education.Conclusion It is recommended to use the target-oriented therapy for early fluid resuscitation management,and perform the fluid resuscitation immediate-ly after diagnosis,according to the patient's underlying disease,disease changes and monitoring indicators,implement precise early fluid resuscitation in order to reverse pancreatic microcirculation disorder,increase tissue perfusion and improve the patient's prognosis.

Objective Explore the key factors and the type of combined role path of medical accident appraisal con-clusion for the medical responsibility,and provide solution countermeasures for the reduction of medical accidents and the construction of a harmonious doctor-patient relationship.Methods Qualitative comparative analysis(QCA)was used to study 125 cases of medical accident appraisal center in a certain province from 2015 to 2019.The fsQCA software was used to detect the necessity of single factor and the configuration path of multiple factors.Results There were three solutions to the configuration of medical liability for medical accidents,with an solution consisten-cy of 0.853 659 and an overall coverage rate of 0.603 448;draw three paths for the conclusion of medical liability,and summarize three types of combined effects:medical institution management vacancy type,medical staff techni-cal negligence type,and comprehensive effect type of both doctors and patients.Conclusion Attaching importance to institutional management is the basis for evading medical liabilities,standardizing medical staff's diagnosis and treatment behavior is the core to reduce medical accidents,and strengthening humanistic concepts and doctor-pa-tient communication are the key to prevent medical accidents.

Platelet transfusion is one of the critical clinical therapies of neonatal thrombocytopenia and significant preventive measures of bleeding diseases in preterm infants.The platelet transfusion rate is high in clinical practice，whereas some controversies emerge in its clinical application.Platelet transfusion decision-making should take into account the platelet count and the causes of thrombocytopenia.In addition，the presence of bleeding tendency and platelet effects on other systemic disorders should be considered.Clinicians often need to make rapid decisions about whether to transfuse platelets in a critically situation.On the basis of the comprehensive overview of issues that are closely pertinent to the field of clinical practice，this article is dedicated to elucidate the advancements in clinical research pertaining to neonatal platelet transfusions，aiming to serve as a reference for clinicians when making transfusion decisions and to chart a course for future clinical investigations.

Objective:To compare the clinical effect of transaxillary non-inflatable endoscopic surgery and traditional open thyroid surgery in the treatment of PTC. Methods:A retrospective analysis was performed on 342 patients with PTC treated in the Otorhinolaryngology Department of Qilu Hospital of Shandong University from December 2020 to December 2022. There were 73 males and 269 females, aged 16-72 years, who underwent unilateral non-inflatable transaxillary endoscopic thyroid surgery（endoscopic group） and unilateral traditional open thyroid surgery（open group）. There were 108 patients in the endoscopic group and 234 in the open group. Results:The endoscopic group was lower in age（37.1±9.4 vs 43.5±11.2） years and BMI（23.4±3.4 vs 25.7±3.8 ）kg/m² than that in the open group, and the difference was statistically significant（t was 5.53, 5.67 respectively, P<0.01）. There was no significant difference in hospitalization days between the two groups（P>0.05）. The logarithmic curve of the operation time showed a smooth downward trend, and the overall operation time of the endoscopic group was relatively consistent. There was no significant difference in intraoperative blood loss between the endoscopic group（13.3±3.2） mL and the open group（14.7±6.3） mL（P>0.05）, but the operation time（130.1±37.9） min was longer than that in the open group（57.4±13.7） min, and the difference was statistically significant（t=19.40, P<0.01）. There was no significant difference in complications such as temporary recurrent laryngeal nerve injury within 3 days after operation between the two groups（P>0.05）. The aesthetic satisfaction score of the surgical incision and the incision concealment effect score in the endoscopic group were higher than those in the open group, and the difference was statistically significant（P<0.05）. Conclusion:Compared with traditional open thyroidectomy, transaxillary non-inflatable endoscopic thyroidectomy has more advantages in the concealment and aesthetics of postoperative incision. Although the former has longer operation time and more drainage, it is still a safe and feasible surgical method with good postoperative clinical effect.
Male ; Female ; Humans ; Thyroid Neoplasms/surgery* ; Retrospective Studies ; Neck ; Thyroidectomy/methods* ; Endoscopy/methods*

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Objective:To evaluate the effect of age factors on the pharmacodynamics of intranasal dexmedetomidine for sedation in the pediatric patients undergoing transthoracic echocardiography(TTE).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients, aged 1-24 months, undergoing TTE from August 2019 to May 2022, were selected. This trial was performed in two parts. Part Ⅰ Pediatric patients were divided into 4 age groups: 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The initial dose of dexmedetomidine was 2.0 μg/kg in 0.1 μg/kg increment/decrement. The dose of dexmedetomidine was determined by using modified Dixon′s up-and-down method. The ED 50 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated by the Dexon-Massey method. Part Ⅱ One hundred patients were divided into 4 age groups ( n= 25 each): 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The 4 groups were further divided into 5 subgroups ( n=5 each) according to the dose of dexmedetomidine: 2.1 μg/kg subgroup, 2.2 μg/kg subgroup, 2.3 μg/kg subgroup, 2.4 μg/kg subgroup, and 2.5 μg/kg subgroup. Part Ⅰ and part Ⅱ trials were combined, and the ED 95 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated using the probit method. Results:A total of 220 pediatric patients were enrolled. There was no significant difference in ED 50 and ED 95 of dexmedetomidine intranasally administered for sedation among groups ( P>0.05). Conclusions:The pharmacodynamics of intranasal dexmedetomidine for sedation shows no significant difference in age in the pediatric patients aged 1-24 months undergoing TTE.

Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.