Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective The aim of this study was to analyze the value of quantitative parameters of dynamic contrast en-hanced magnetic resonance imaging(DCE-MRI)combined with the detection of non-SMC condensing Ⅰ complex subunit H(NCAPH)in the diagnosis of early breast cancer.Methods Ninety-six patients with breast nodules who were treated in the depart-ment of Breast Surgery at Longgang District Maternity&Child Healthcare Hospital in Shenzhen from March 2020 to March 2022 were selected as the study objects.DCE-MRI examination was performed on all patients,and transport constant(Ktrans)and rate constant(Kep)were recorded.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of serum NCAPH mRNA.Based on the results of pathological examination as the gold standard,the patients with breast nodules diag-nosed pathologically as the benign group and the patients with breast cancer as the breast cancer group,the differences of DCE-MRI quantitative parameters Ktrans,Kep and serum NCAPH mRNA between the benign group and the breast cancer group were compared.The accuracy,sensitivity and specificity of serum NCAPH mRNA and their combination in the diagnosis of early breast cancer were different.Kappa test was used to compare the consistency with the pathological results.Results The results of pathological examina-tion confirmed that there were 31 benign nodules and 65 breast cancer in 96 patients with breast nodules.Ktrans,Kep and NCAPH mRNA in the breast cancer group were significantly higher than those in the benign group(P<0.05);The AUC of Ktrans,Kep and NCAPH in the diagnosis of early breast cancer was 0.944,which was significantly higher than that of Ktrans and Kep alone,with the sensitivity and specificity of 96.92% and 77.42% ,respectively;Ktrans and Kep combined with NCAPH detected 7 false positives and 2 false negatives,with a Kappa value of 0.776(P<0.05),which was consistent with the pathological results;The sensitivity of DCE-MRI quantitative parameters combined with NCAPH in the diagnosis of early breast cancer was significantly higher than that of DCE-MRI quantitative parameters and serum NCAPH alone(P<0.05).Conclusion The expression of Ktrans,Kep and serum NCAPH mRNA in breast cancer patients with DCE-MRI quantitative parameters is high.Ktrans,Kep combined with serum NCAPH detection has certain clinical values in the diagnosis of early breast cancer.

Objective The aim of this study was to analyze the value of quantitative parameters of dynamic contrast en-hanced magnetic resonance imaging(DCE-MRI)combined with the detection of non-SMC condensing Ⅰ complex subunit H(NCAPH)in the diagnosis of early breast cancer.Methods Ninety-six patients with breast nodules who were treated in the depart-ment of Breast Surgery at Longgang District Maternity&Child Healthcare Hospital in Shenzhen from March 2020 to March 2022 were selected as the study objects.DCE-MRI examination was performed on all patients,and transport constant(Ktrans)and rate constant(Kep)were recorded.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of serum NCAPH mRNA.Based on the results of pathological examination as the gold standard,the patients with breast nodules diag-nosed pathologically as the benign group and the patients with breast cancer as the breast cancer group,the differences of DCE-MRI quantitative parameters Ktrans,Kep and serum NCAPH mRNA between the benign group and the breast cancer group were compared.The accuracy,sensitivity and specificity of serum NCAPH mRNA and their combination in the diagnosis of early breast cancer were different.Kappa test was used to compare the consistency with the pathological results.Results The results of pathological examina-tion confirmed that there were 31 benign nodules and 65 breast cancer in 96 patients with breast nodules.Ktrans,Kep and NCAPH mRNA in the breast cancer group were significantly higher than those in the benign group(P<0.05);The AUC of Ktrans,Kep and NCAPH in the diagnosis of early breast cancer was 0.944,which was significantly higher than that of Ktrans and Kep alone,with the sensitivity and specificity of 96.92% and 77.42% ,respectively;Ktrans and Kep combined with NCAPH detected 7 false positives and 2 false negatives,with a Kappa value of 0.776(P<0.05),which was consistent with the pathological results;The sensitivity of DCE-MRI quantitative parameters combined with NCAPH in the diagnosis of early breast cancer was significantly higher than that of DCE-MRI quantitative parameters and serum NCAPH alone(P<0.05).Conclusion The expression of Ktrans,Kep and serum NCAPH mRNA in breast cancer patients with DCE-MRI quantitative parameters is high.Ktrans,Kep combined with serum NCAPH detection has certain clinical values in the diagnosis of early breast cancer.

Objective:To explore the awareness and experiences of elder abuse among staff in nursing homes.Methods:Qualitative studies on elder abuse by nursing home staff were systematically searched in databases, including China Biology Medicine disc, Wanfang data, Web of Science, and PubMed, up to August 15, 2023. A meta-synthesis approach was employed to categorize and integrate the findings.Results:Fourteen articles were included, yielding 93 themes. After repeated reading, analysis, and comparison, similar results were categorized into 12 new categories, synthesized into three integrated outcomes: causes of elder abuse, forms of elder abuse, and strategies for prevention and intervention of elder abuse.Conclusions:Staff should pay attention to the issue of elder abuse in nursing homes, establish closer connections between institutions, the aged, and their families, and promote healthy aging within these facilities.

Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1-/-)and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAP-induced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1-/- mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a 11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.

Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR₁) and negative minimal residual disease (MRD^-) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR₁/MRD^- from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR₁/MRD^- was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion Allo-HSCT for candidate patients without further consolidation when CR₁/MRD^- was attained was feasible.