Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Reducing the mother-to-child transmission of hepatitis B virus(HBV)is crucial for achieving HBV elimination.Launched in July 2015 at the Great Hall of the People in Beijing,China,the"Zero Hepatitis B Mother-to-Child Transmission Project"(Shield Project)is a public welfare initiative integrating scientific prevention and applied research and aims to perform standardized management of pregnant women with hepatitis B using the mobile application of"Shield Project",in order to further reduce or eliminate the mother-to-child transmission of HBV.At present,the Shield Project has expanded nationwide,offering detailed implementation strategies,successful practices,and reliable data to support the global effort to eliminate the mother-to-child transmission of HBV.This article introduces the implementation strategies and outcomes of the Shield Project in four representative cases,in order to provide strong evidence for further understanding and preventing the mother-to-child transmission of HBV.

Objective:To investigate the effects and mechanisms of zinc ion-loaded composite hydrogel (hereinafter referred to as the zinc-containing hydrogel) on infected full-thickness skin defect wounds in diabetic mice.Methods:This study was an experimental study. A poly (glycerol sebacate)-co-poly(ethylene glycol)-g-catechol prepolymer/quaternized-chitosan hydrogel (hereinafter referred to as the simple hydrogel) and a solid-state zinc-containing hydrogel with porous and good adhesion by adding zinc ions to the simple hydrogel were prepared. The release rate of zinc ions from the zinc-containing hydrogel after immersion in phosphate buffer solution (PBS) for 14 days was calculated. The concentration of methicillin-resistant Staphylococcus aureus (MRSA) cultured for 2 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The scavenging ability of the simple hydrogel, zinc-containing hydrogel, and PBS for 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2, 4, 6-trinitrophenyl) hydrazyl (DPPH) was detected using microplate reader to reflect the ability of oxygen free radical removal. The length of vessels formed by human umbilical vein endothelial cells (HUVECs) cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The cell viability of L929 cells cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was detected using the cell counting kit-8. The mouse red blood cell suspension was divided into blank control group treated with PBS, simple hydrogel group, zinc-containing hydrogel group, and Triton X-100 group treated with corresponding solution. Hemolysis was detected using microplate reader after 2 hours of treatment, and the hemolysis rate was calculated. All experiments had a sample size of 3. Twenty-one C57BL/6J mice aged 6-8 weeks were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back spine and infected with MRSA. Mice were divided into blank control group treated with PBS, simple hydrogel group, and zinc-containing hydrogel group treated with the corresponding hydrogel. Three days after injury, bacterial concentration in the wounds were measured in all groups of mice ( n=4). On day 0 (immediately), 3, 7, and 14 after injury, the wound infection status of mice was generally observed and the wound healing rate was calculated ( n=5). Hematoxylin-eosin staining and Masson staining were used to detect new epithelium and collagen formation in the wounds of mice on day 14 after injury. Immunofluorescence staining was used to detect neovascularization and distribution of M2 macrophages in the wounds of mice. Results:After immersion for 14 days, the release rate of zinc ions of the zinc-containing hydrogel was (70.5±4.6)%. Compared with the zinc-containing hydrogel, the bacterial concentration was significantly increased after 2 hours of culture with PBS and the simple hydrogel ( P<0.05). The DPPH scavenging rate of the zinc-containing hydrogel was significantly higher than that of PBS and the simple hydrogel (with P values all <0.05). The length of vessels formed by HUVECs cultured for 24 hours with the zinc-containing hydrogel was significantly longer than that cultured with PBS ( P<0.05). Compared with PBS and the simple hydrogel, the cell viability of L929 cells cultured for 24 hours with the zinc-containing hydrogel was significantly higher ( P<0.05). After 2 hours of incubation, compared with that in Triton X-100 group, the hemolysis rate of red blood cells in blank control, simple hydrogel, and zinc-containing hydrogel groups was significantly reduced ( P<0.05); and the hemolysis rate of red blood cells in the latter three groups was similar ( P>0.05). On day 3 after injury, the bacterial concentration in the wounds of mice in zinc-containing hydrogel group was significantly lower than that in blank control and simple hydrogel groups (with P values all <0.05). From day 3 to day 14 after injury, the wounds of mice in all the three groups were gradually healing, and on day 14 after injury, the wounds of mice in the zinc-containing hydrogel group were basically healed. On day 7 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (72.4±8.4)%, which was significantly higher than that of blank control and simple hydrogel groups, being (31.6±6.7)% and (44.7±5.4)%, respectively(with P values all< 0.05). On day 14 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (92.7±4.3)%, which was significantly higher than (73.5±7.4)% in blank control group ( P<0.05). On day 14 after injury, compared with that in blank control and simple hydrogel groups, the newly formed epidermis in mice wound of zinc-containing hydrogel group was longer and thicker, with more collagen deposition, and a more abundant distribution of new vessels and M2 macrophages. Conclusions:The zinc-containing hydrogel exhibits good biocompatibility, oxygen free radical scavenging capacity, and antimicrobial effects both in vitro and in vivo, as well as angiogenic promotion capability. It can provide sustained release of zinc ions to promote re-epithelialization and collagen synthesis, thus enhancing the healing of infected full-thickness skin defect wounds in diabetic mice.

In recent years, infectious pathogens have received sustained attention because of their serious impact on the world′s health and socio-economic infrastructure. The existing common detection methods lack a certain sensitivity and specificity, the process is tedious, and they rely on more expensive auxiliary instruments and equipment. On the other hand, clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats associated protein (CRISPR/Cas) has been widely used in the monitoring of infectious diseases due to its high specificity, sensitivity, and rapid programmable characteristics, and has shown important potential significance in the research of new biosensors in nucleic acid detection. This paper describes the functional mechanism of Cas protein commonly used in CRISPR/Cas system, summarizes the latest research progress of new biosensor technology based on CRISPR/Cas system in the field of infectious disease detection, and looks forward to the technical problems to be solved and the future development direction. With more research advancement, more types of biosensing platforms based on CRISPR/Cas system are expected to be developed, paving the way for the application of POCT in the field of rapid pathogen detection.

Humans ; Pulmonary Disease, Chronic Obstructive ; Smoke/adverse effects* ; Tobacco ; Tobacco Smoke Pollution