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

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

Objective:To explore the dynamic change trajectory and influencing factors of postoperative fatigue (POF) in patients with early digestive tract cancer undergoing endoscopic submucosal dissection (ESD), so as to provide theoretical basis for individualized management of such patients.Methods:Using cross-sectional survey and convenient sampling method, the patients who underwent ESD for early cancer of digestive tract in the endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June 2024 were selected as the research objects. The questionnaires were conducted at 30 min, 24 h, 3 days, 5 days, 7 days after ESD with Christensen's postoperative fatigue score. Spearman test was used to analyze the correlation between pain, insomnia and POF. The latent variable growth model was used to identify the potential categories of POF trajectory, and the influencing factors were analyzed by Logistic regression.Results:A total of 232 patients were finally induded, with ages of 19-94(59.53 ± 13.29) years, including 120 males and 112 femalss. The POF level of patients with early cancer of digestive tract showed a downward trend one week after operation. Three postoperative fatigue trajectories were fitted, 9.05% in moderate or severe fatigue low-speed smooth descent group (C1 group); 32.76% in moderate fatigue first decreased quickly and then slowly group (C2 group) and 58.19% in mild fatigue continuous decline group (C3 group). The result of Logistic regression analysis showed that, compared with C1 group, people without religious beliefs were morelikely to enter C2 group [ β = 1.572, OR = 4.818(1.033 - 22.465), P<0.05]; compared with C3 group, patients with high pain level and severe insomnia degree were likely to enter C1 [ β = 2.621, 0.663, OR were 13.754(2.692 - 70.283) and 1.942(1.429 - 2.638), both P<0.05] and C2 [ β = 2.010, 0.491, OR were 7.464(1.890 - 29.482) and 1.634(1.348 - 1.982), both P<0.05] group. Conclusions:There were three potential types of POF in patients with early digestive tract cancer ESD. Medical staff should pay attention to patients with severe insomnia, intense pain and religious beliefs, and give staged fatigue assessment and individualized intervention, so as to reduce the level of POF and promote rapid recovery.

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

Objective:To explore the dynamic change trajectory and influencing factors of postoperative fatigue (POF) in patients with early digestive tract cancer undergoing endoscopic submucosal dissection (ESD), so as to provide theoretical basis for individualized management of such patients.Methods:Using cross-sectional survey and convenient sampling method, the patients who underwent ESD for early cancer of digestive tract in the endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June 2024 were selected as the research objects. The questionnaires were conducted at 30 min, 24 h, 3 days, 5 days, 7 days after ESD with Christensen's postoperative fatigue score. Spearman test was used to analyze the correlation between pain, insomnia and POF. The latent variable growth model was used to identify the potential categories of POF trajectory, and the influencing factors were analyzed by Logistic regression.Results:A total of 232 patients were finally induded, with ages of 19-94(59.53 ± 13.29) years, including 120 males and 112 femalss. The POF level of patients with early cancer of digestive tract showed a downward trend one week after operation. Three postoperative fatigue trajectories were fitted, 9.05% in moderate or severe fatigue low-speed smooth descent group (C1 group); 32.76% in moderate fatigue first decreased quickly and then slowly group (C2 group) and 58.19% in mild fatigue continuous decline group (C3 group). The result of Logistic regression analysis showed that, compared with C1 group, people without religious beliefs were morelikely to enter C2 group [ β = 1.572, OR = 4.818(1.033 - 22.465), P<0.05]; compared with C3 group, patients with high pain level and severe insomnia degree were likely to enter C1 [ β = 2.621, 0.663, OR were 13.754(2.692 - 70.283) and 1.942(1.429 - 2.638), both P<0.05] and C2 [ β = 2.010, 0.491, OR were 7.464(1.890 - 29.482) and 1.634(1.348 - 1.982), both P<0.05] group. Conclusions:There were three potential types of POF in patients with early digestive tract cancer ESD. Medical staff should pay attention to patients with severe insomnia, intense pain and religious beliefs, and give staged fatigue assessment and individualized intervention, so as to reduce the level of POF and promote rapid recovery.

With the rapid development of industry and economy,the emergence of a large number of chemicals has made of risk management more difficult.Traditional risk assessment relies on animal experiments for toxicity testing.However,animal experiments are time-consuming,costly,and unable to meet the practical needs of risk assessment.The increasing maturity of toxicity testing alternative technologies signifies the possibility of rapid,sensitive,and accurate identification of chemical toxicity.This article focuses on the research and applications of alternative toxicity testing by reviewing the background,developments,and current research at home and abroad.It also discusses the progress in alternative testing methods in such areas as cosmetics and food safety risk assessment and explores the problems with the development of alternative testing technologies and risk assessment in China.This review aims to provide a reference for the system construction of cosmetics health risk assess-ment in China.

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call the "third-party framing effect". In these experiments, participants observed an anonymous perpetrator deciding whether to keep her/his economic benefit while exposing a victim to a risk of physical pain (described as "harming others" in one condition and "not helping others" in the other condition), then they had a chance to punish that perpetrator at their own cost. Our results showed that the participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting a framing effect. Self-reported anger toward perpetrators mediated the relationship between empathy toward victims and the framing effect. Meanwhile, activation of the insula mediated the relationship between mid-cingulate cortex activation and the framing effect; the functional connectivity between these regions significantly predicted the size of the framing effect. These findings shed light on the psychological and neural mechanisms of the third-party framing effect.
Empathy ; Female ; Gyrus Cinguli ; Humans ; Neuroimaging ; Pain ; Punishment/psychology*

Objective: To study the clinical significance of serum calcitonin in the diagnosis and treatment of medullary thyroid carcinoma and to analyze its cost-benefit. Methods: One hundred and forty one patients with medullary thyroid carcinoma who undertook calcitonin test and frozen pathological examination were enrolled in this study from Oct 2012 to Mar 2018. Using the method of χ² test, the positive rate of calcitonin test and frozen pathological examination in diagnosis of medullary thyroid carcinoma(MTC) were compared. Firstly, we compared the correct checkout cost of calcitonin test and that of frozen pathological examination (total number of patients×cost of examination/the correctly detected number of patients) . Secondly, we calculated whether calcitonin test help patients save money(average cost of treatment in hospital for MTC×number of patients who were evaluated to be candidate for surgery-cost of calcitonin test×total number of patients)/total number of patients. Results: 139 patients were positive in calcitonin test among 141 patients, and the positive rate was 98.58%. 91 patients were positive in frozen pathological examination, and the positive rate was 64.54% (χ²=97.821, P<0.000 1) . Cost-benefit analysis showed that the correct checkout cost of calcitonin test and frozen pathological examination were 71.01 yuan and 426.10 yuan, also,1 371 938.64 yuan could be saved totally and 9 730.06 yuan could be saved per patient because of calcitonin test. Conclusion Serum calcitonin test had a significant effect on the diagnosis and treatment of medullary thyroid carcinoma and was economical and practical.

Objective To evaluate the changes in anterior chamber structure of pelvic floor before and after total hysterectomy with transperineal ultrasonography.Methods Forty-five patients who would receive total hysterectomy were enrolled.The structures of the anterior pelvic floor were observed with transperineal ultrasonography 1 day pre-operation and 1,3 and 6 months after operation.The parameters at rest and max Valsalva were recorded and calculated,including the bladder neck-symphyseal distance (BSD),bladder neck descent (BND),urethral rotation angle (UR) and posterior urethrovesical angle (PUA).The changes of the parameters at different time were analyzed statistically.Results BSD at max Valsalva,BND,UR and PUA at max Valsalva at different time were significantly different (all P＜0.05).Compared with those preoperative,BSD at max Valsalva decreased (H=2.627,P=0.009) and BND increased (q=-3.095,P=0.002) 3 months after operation,BSD at max Valsalva decreased (H=4.379,P＜0.001),BND (q=-4.379,P＜ 0.001),UR (H=-2.861,P=0.004) and PUA at max Valsalva (q=-2.686,P=0.007) increased 6 months after operation.The remaining parameters were not significantly different between every two time points (all P ＞ 0.05).Conclusion The changes of BSD,BND at max Valsalva,UR and PUA at max Valsalva occur at the initial period after the total hysterectomy.The total hysterectomy can damage the pelvic floor and early pelvic floor rehabilitation need to he provided.