Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

The accurate deduction of postmortem interval is a difficult and extremely critical task in the field of forensic pathology and criminal investigation.In recent years,physics,chemistry,microbiology,immunology,entomology,molecular biology and other disciplines have been on the rise,and special staining,spectroscopy,mass spectrometry,chromatography,radiographic and other techniques have been developed,and methods for postmortem interval inference are increasing,among which immunolabelling techniques have played an important role.In this paper,we systematically reviewed the domestic and foreign relevant studies on the postmortem interval inference using of immunolabelling techniques,including immunohistochemistry,immunoblotting,immunofluorescence,radioimmunoassay,etc.We summarized and analyzed the research progress on these techniques in postmortem interval inference,with the aim of exploring the ideas for the study of postmortem interval inference in forensic pathology,and provide reference for better applying them in forensic practice.

【Objective】 To investigate the confirmatory status of HIV-1 antibody detection and Western blot (WB) test among voluntary blood donors in Wuhu, and to explore the strategies and methods to further ensure blood quality and safety. 【Methods】 Blood samples were preliminarily screened by ELISA and NAT, and the reactive samples were sent to Wuhu CDC for further WB test of HIV-1 antibody. The confirmation results of HIV-1 antibodies of voluntary blood donors in Wuhu in the past 10 years were retrospectively collected. The characteristics of WB bands of positive samples were analyzed, and the demographic characteristics of HIV-infected voluntary blood donors were sorted out. 【Results】 A total of 354 864 blood samples from voluntary blood donors in Wuhu during January 2011 to May 2021 were investigated, among which 42 were confirmed HIV positive (HIV-1 antibody positive in 41, and solo HIV-RNA reactive in 1), with a total HIV positive rate of 11.8/100 000(42/354 864). Statistical differences were found in gender [males 97.6% (41/42) vs females 2.4% (1/42)], marital status [unmarried 17.3/100 000 vs married 8.0/100 000] and occupation [staff/workers 37.5/100 000 vs students11.4/100 000 vs others 7.7/100 000]. Among the positive samples, the yield rate of WB bands gp160 was 100% (41/41), both gp41 and p24 were 97.6% (40/41),, and p55 was the lowest 46.3% (19/41). P51 and P66 presented the highest yield consistency (Kappa=1.000, P<0.05). Four samples were solo HIV-RNA reactive, and one of them was>5 000 cps/mL by viral load (VL) testing, indicating HIV window period infection. 【Conclusion】 HIV infection statistically affected male donors more than females in Wuhu area, and most were early infection that revealed by WB band analysis. NAT plays an important role in the detection and confirmation of HIV infection during the window period, and is essential for blood safety.

【Objective】 To analyze the HIV infection among voluntary blood donors in Wuhu area, so as to provide effective data for improving blood donation recruitment strategies and clinical safe blood use. 【Methods】 All reactive samples from HIV screening among voluntary blood donors in Wuhu from January 2017 to September 2020 were selected and sent to Wuhu CDC for confirmation test.The receiver operating characteristic (ROC) curve was used to compare the accuracy of enzyme-immune reagents. The optimal critical value of ELISA was used to analyze the setting of serological gray area. The preliminary screening S/CO values of confirmed positive, negative and indeterminate samples were compared, and the significance of differences were analyzed by SPSS 22.0 software. 【Results】 75 cases of initially HIV reactive samples were submitted for testing: 17 cases were confirmed positive, 17 indeterminate and 41 negative.The area under curve (AUC) of the 4th generation anti-HIV ELISA reagent was greater than that of the 3rd generation reagent, and the 4th generation reagent was better than the 3rd generation reagent in accuracy. All the 17 confirmed positive samples had high S/CO reactivity with duplicate reagents, and the initial screening S/CO value was significantly higher than that of confirmed negative and indeterminate samples (P<0.05). There was no significant statistical difference in S/CO values between confirmed negative and indeterminate results (P>0.05). 【Conclusion】 Voluntary blood donors in Wuhu is a middle-endemic population for HIV infection. The setting of grey areas for serological testing is of little significance. Blood safety should be further guaranteed through standardized pre-donation interventions, sensitive nucleic acid detection technologies and shared regional data platforms.

Head and neck squamous cell carcinoma (HNSCC) is the most common pathological type in head and neck tumor. It can evade immune response through various mechanisms such as immune tolerance, immune escape, high expression of immune checkpoint molecules in tumor cells and T cell signal destruction. In recent years, immune checkpoint inhibitor therapy has made a breakthrough in HNSCC patients. From second-line therapy to first-line therapy in recurrent and metastatic HNSCC, then adjuvant therapy in locally advanced HNSCC patients, several clinical studies of immune checkpoint inhibitors (ICIs) therapy have been showed good therapeutic effects. In addition, a variety of combination therapies such as ICI combination with targeted therapy, ICI, radiotherapy and other methods currently being studied. However, the beneficiaries of immune checkpoint inhibitors are still unclear, and how to effectively combine immune checkpoint inhibitors with chemotherapy, radiotherapy, targeted therapy and surgery is currently being explored. In the period of individualized treatment, the treatment strategies for HNSCC are experiencing new changes, facing more options and challenges. In this article, we will review some major clinical studies of immune checkpoint inhibitor therapy in squamous cell carcinoma of the head and neck in recent years.

OBJECTIVE：To i mprove the transfer rate and purity of oleanolic acid and ursolic acid in total triterpenoids from Ligustrum lucidum ，so as to optimize the purification technology. METHODS ：Oleanolic acid and ursolic acid were used as representative components of total triterpenoids ，and their contents were determined by HPLC. The determination was performed on Thermo BDS Hypersil C 18 column with mobile phase consisted of methanol- 0.02％ ammonium acetate solution （80∶20，V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and column temperature was 30 ℃. The sample size was 20 μ L. In single factor tests，using transfer rate of oleanolic acid and ursolic acid as index ，the effects of water precipitation temperature and time ，the amount of redissolved ethanol on the purification technology was investigated ；using transfer rate and purity of two components as indexes ，the effects of the amount of activated carbon and volume fraction of crystallization ethanol were investigated. Based on it ，using the amount of redissolved ethanol and activated carbon ，volume fraction of crystallization ethanol as factors ，Box-Behnken response surface methodology was used to optimize the purification technology ，and validation tests were performed. RESULTS ：The optimal purification technology was adding 4-fold（mL/g，the same below ）water in L. lucidum concentrated solution ，placing for 2 hours at 0 ℃（water precipitation ）；adding 1-fold ethanol to dissolve （redissolution）； adding 4％ activated carbon （edulcoration）；finally adding water to adjust the volume fraction of ethanol to 80％，placing at 4 ℃ for 12 hours（crystallization），centrifuging and drying. The results of 3 times of validation tests showed that the transfer rates of oleanolic acid and ursolic acid in total triterpenoids prepared by optimized technology were 61.11％ and 65.78％，the purities of them were 53.44％ and 19.79％，and RSDs were both lower than 3％. CONCLUSIONS ：The optimized purification technology has high extraction efficiency and simple operation ，which can be used for industrial production of purification of total triterpenoids from L. lucidum and the development of corresponding preparations.

Objective:To investigate the fertility needs and outcome of pregnancy in patients with young breast cancer in China.Methods:A retrospective cross-sectional investigation was conducted on 374 young breast cancer women from Cancer Hospital, Chinese Academy of Medical Sciences. Young patients with breast cancer were defined as patients who got initial diagnosis of breast cancer at age no more than 40 years old. We conducted a questionnaire survey and collected clinical data from medical chart. Logistic regression model was used to analyze the possible factors influencing patients′ fertility intention.Results:308 young women with breast cancer completed questionnaires, and the response rate was 82.4%. 81 patients (26.3%) had fertility needs after diagnosis. Of them, 6 cases took active measures to preserve fertility. 72 patients (23.4%) received fertility counseling during treatment. 7 patients were successfully pregnant, including four cases who delivered normally. Multivariate logistic regression analysis showed that patients under 35 years old ( OR=4.81), bachelor degree or above ( OR=3.26), receiving breast-conserving surgery ( OR=2.15) and childless patients ( OR=3.03) were more likely to have fertility needs after diagnosis of breast cancer (all P<0.05). Conclusions:The fertility needs of young breast cancer women in China are gradually increasing. Healthcare providers associated with tumor patients should actively offer corresponding fertility consultation and individualized diagnosis and therapy plans for patients with fertility needs.

Objective:To investigate the fertility needs and outcome of pregnancy in patients with young breast cancer in China.Methods:A retrospective cross-sectional investigation was conducted on 374 young breast cancer women from Cancer Hospital, Chinese Academy of Medical Sciences. Young patients with breast cancer were defined as patients who got initial diagnosis of breast cancer at age no more than 40 years old. We conducted a questionnaire survey and collected clinical data from medical chart. Logistic regression model was used to analyze the possible factors influencing patients′ fertility intention.Results:308 young women with breast cancer completed questionnaires, and the response rate was 82.4%. 81 patients (26.3%) had fertility needs after diagnosis. Of them, 6 cases took active measures to preserve fertility. 72 patients (23.4%) received fertility counseling during treatment. 7 patients were successfully pregnant, including four cases who delivered normally. Multivariate logistic regression analysis showed that patients under 35 years old ( OR=4.81), bachelor degree or above ( OR=3.26), receiving breast-conserving surgery ( OR=2.15) and childless patients ( OR=3.03) were more likely to have fertility needs after diagnosis of breast cancer (all P<0.05). Conclusions:The fertility needs of young breast cancer women in China are gradually increasing. Healthcare providers associated with tumor patients should actively offer corresponding fertility consultation and individualized diagnosis and therapy plans for patients with fertility needs.

To explore the prognostic value of heat shock protein-90α (HSP-90α) plasma levels on breast cancer and non-breast malignant tumors, monitoring the response of chemotherapy, and the predictive value of cancer recurrence and metastasis. Methods: A total of 615 female patients were enrolled between June 2016 and September 2016 in Cancer Hospital, Chinese Academy of Medical Sciences, who were divided into the examination (n=389) and control (n=216) groups. The former group consisted of static (n=289) and dynamic (n=110) groups, which were analyzed by stages, histological and molecular type, and so on. The latter group in-cluded healthy people (n=103), and those with breast benign tumors (n=51) and non-breast malignant tumors (n=62). In all the plasma samples, HSP-90α was detected using a double-antibody enzyme-linked immunosorbent assay. The receiving-operating characteristic curve was used to analyze the effectiveness of plasma HSP-90α in the diagnosis of breast cancer. Wilcoxon＇s rank test and the Kruskal-Wallis test were used to analyze the association between clinical characteristics and levels of plasma HSP-90α. Results: The levels of plasma HSP-90α were significantly higher in patients with breast cancer than in healthy controls (P<0.001). When the cut-off value was set as 59.7 ng/mL for the diagnosis of breast cancer and 43.22 ng/mL for disease recurrence, the areas under the curve were 0.834 and 0.877, sensitivities were 90.3% and 95.7%, and specificities were 78.6% and 74.5%, respectively. The levels of plasma HSP-90α sig-nificantly decreased after achieving a response to neoadjuvant chemotherapy or surgery (P<0.05). Conclusions: Plasma HSP-90α has good clinical value in the diagnosis and monitoring of response and recurrence in breast cancer.

V(E) acetate-loaded methoxy poly(ethylene glycol)-b-poly(lactic acid) amphiphilic diblock copolymer nano-dispersion (PMV) was prepared by self-emulsification/solvent evaporation method. The drug-loaded amount, size distribution of PMV nanoparticles, and entrapment efficiency of V(E) acetate (V(E)A) were determined by UV and laser particle analyzer. Drug release in vitro was primarily investigated by UV. The results indicate that the size of PMV nanoparticles is less than 300 nm and PMV is largely influenced by preparation methods, property of solvents, V(E)A-fed amount, and the concentration of dispersion. The initial burst release is not observed and the accumulated release is more than 79% after 14 h. This study develops a new formulation for V(E)A and provides an experimental basis for the novel drug delivery systems of V(E)A.
Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; administration & dosage ; chemistry ; Hydrophobic and Hydrophilic Interactions ; Nanoparticles ; Polyesters ; administration & dosage ; Polyethylene Glycols ; administration & dosage ; Vitamin E ; administration & dosage