Objective:To systematically review risk prediction models for frailty in maintenance hemodialysis (MHD) patients.Methods:Relevant literature on frailty risk prediction models for MHD patients were retrieved from PubMed, Web of Science, Embase, Cochrane Library, CINHAL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc from inception to March 25, 2024. Two researchers independently screened the literature and extracted data. The PROBAST tool was used to assess the methodological quality of the prediction models. Meta-analysis of predictive factors was conducted using Stata 16.0 software.Results:A total of 13 studies were included, comprising 19 frailty risk prediction models for MHD patients. All studies exhibited a high risk of bias. Six studies conducted internal validation, and three studies conducted external validation. The area under the receiver operating characteristic curve ( AUC) of the included prediction models ranged from 0.720 to 0.998. Meta-analysis revealed that age [ OR=1.149, 95% CI (1.070, 1.234), P<0.001], female gender [ OR=4.472, 95% CI (1.799, 11.117), P<0.001], nutritional score [ OR=2.650, 95% CI (1.010, 6.970), P=0.048], comorbidities [ OR=1.990, 95% CI (1.500, 2.650), P<0.001], and serum albumin [ OR=0.830, 95% CI (0.790, 0.880), P<0.001] were significant influencing factors for frailty in MHD patients. Conclusions:Risk prediction models for frailty in MHD patients are still in the research stage. Healthcare professionals should pay close attention to frailty risks in older patients, females, those with malnutrition, comorbidities, and low serum albumin levels, and implement timely interventions.

Objective:To systematically review and evaluate risk prediction models for radiation dermatitis in breast cancer patients, providing a reference for developing higher-quality prediction models.Methods:A systematic search was conducted in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database for studies related to risk prediction models for radiation dermatitis in breast cancer patients. The search timeframe was from database inception to February 28, 2024. Two researchers independently screened relevant literature based on inclusion and exclusion criteria, extracted the basic characteristics of the studies, and performed analysis. The included models were assessed for risk of bias and applicability.Results:A total of 8 articles involving 9 models were included, covering a total sample size of 1 291 cases, with 10 to 144 outcome events. The number of predictors ranged from 2 to 10, with common predictors including body mass index, smoking history, and breast volume, radiation dose, etc. The AUC values of the included models ranged from 0.76 to 0.98. The overall risk of bias for the models was relatively high, mainly due to issues related to study design, missing data handling, variable selection, and model validation.Conclusions:Existing risk prediction models for radiation dermatitis in breast cancer patients have certain limitations. It is recommended that future research further improve study designs, validate and optimize existing models, and develop high-performance risk prediction models.

Objective:To systematically review and evaluate risk prediction models for radiation dermatitis in breast cancer patients, providing a reference for developing higher-quality prediction models.Methods:A systematic search was conducted in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database for studies related to risk prediction models for radiation dermatitis in breast cancer patients. The search timeframe was from database inception to February 28, 2024. Two researchers independently screened relevant literature based on inclusion and exclusion criteria, extracted the basic characteristics of the studies, and performed analysis. The included models were assessed for risk of bias and applicability.Results:A total of 8 articles involving 9 models were included, covering a total sample size of 1 291 cases, with 10 to 144 outcome events. The number of predictors ranged from 2 to 10, with common predictors including body mass index, smoking history, and breast volume, radiation dose, etc. The AUC values of the included models ranged from 0.76 to 0.98. The overall risk of bias for the models was relatively high, mainly due to issues related to study design, missing data handling, variable selection, and model validation.Conclusions:Existing risk prediction models for radiation dermatitis in breast cancer patients have certain limitations. It is recommended that future research further improve study designs, validate and optimize existing models, and develop high-performance risk prediction models.

Objective:To systematically review risk prediction models for frailty in maintenance hemodialysis (MHD) patients.Methods:Relevant literature on frailty risk prediction models for MHD patients were retrieved from PubMed, Web of Science, Embase, Cochrane Library, CINHAL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc from inception to March 25, 2024. Two researchers independently screened the literature and extracted data. The PROBAST tool was used to assess the methodological quality of the prediction models. Meta-analysis of predictive factors was conducted using Stata 16.0 software.Results:A total of 13 studies were included, comprising 19 frailty risk prediction models for MHD patients. All studies exhibited a high risk of bias. Six studies conducted internal validation, and three studies conducted external validation. The area under the receiver operating characteristic curve ( AUC) of the included prediction models ranged from 0.720 to 0.998. Meta-analysis revealed that age [ OR=1.149, 95% CI (1.070, 1.234), P<0.001], female gender [ OR=4.472, 95% CI (1.799, 11.117), P<0.001], nutritional score [ OR=2.650, 95% CI (1.010, 6.970), P=0.048], comorbidities [ OR=1.990, 95% CI (1.500, 2.650), P<0.001], and serum albumin [ OR=0.830, 95% CI (0.790, 0.880), P<0.001] were significant influencing factors for frailty in MHD patients. Conclusions:Risk prediction models for frailty in MHD patients are still in the research stage. Healthcare professionals should pay close attention to frailty risks in older patients, females, those with malnutrition, comorbidities, and low serum albumin levels, and implement timely interventions.

Objective:To explore the relationship between anhedonia and suicidal ideation and the effects of anhedonia on suicidal ideation in patients with first-episode untreated depressive disorder.Methods:Totally 106 in-patients who met the diagnostic criteria for depressive disorder of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were invited to participate in the study.Anhedonia,depressive symptoms and sui-cidal ideation were assessed with the Snaith-Hamilton Pleasure Scale(SHAPS),Hamilton Depression Scale(HAMD)and Beck Scale for Suicide Ideation(BSI),respectively.If both items 4 and 5 of BSI were 0,it indicated non-suicidal ideation,the subjects were divided into a group of suicidal ideation(n=66)and a group non-suicidal ideation(n=40).Spearman correlation analysis and multivariate binary logistic regression analysis were used for a-nalysis.Results:The correlation between the scores of SHAPS and HAMD was not statistically significant(P＞0.05).The SHAPS scores were positively correlated with the BSI scores(r=0.70,P＜0.01).Meanwhile,binary logistic regression analysis showed that anhedonia was one of a risk factor for suicidal ideation(OR=2.34,95％CI:1.58-3.47,P＜0.001).Conclusion:It suggests that anhedonia maybe partially independent of other depres-sive symptoms and it is one of the risk factors for suicidal ideation in first-episode untreated patients with depressive disorder.

Objective:To explore the effects of miR-21-5p exosomes derived from human umbilical cord mesenchymal stem cells on apoptosis of human granular cells.Methods:A granular cell apoptosis model was constructed by treating KGN cells with different concentrations (0 μmol/L, 30 μmol/L, 60 μmol/L, and 100 μmol/L) of phosphoramide nitrogen mustard for 48 h. The mRNA and protein levels of bax and bcl2 were detected using qPCR and Western blotting, respectively. The apoptosis rate was measured using flow cytometry to screen for the optimal concentration of phosphoramide nitrogen mustard for constructing an apoptosis model. Hsa-miR-21-5p overexpression plasmid was used for instantaneously transfecting human umbilical cord mesenchymal stem cells, and the expression level of hsa-miR-21-5p was detected by qPCR. The miR-21-5p exosomes were separated and identified by flow cytometry and electron microscope. Different concentrations (5 μg/mL, 10 μg/mL and 15 μg/mL) of miR-21 exosomes were added into successful KGN cell apoptosis model to overexpress miR-21. The mRNA and protein levels of bax and bcl2 were detected using qPCR and Western blotting, respectively. PKH-26 was used to trace the position of human granular cells. Results:The levels of bax mRNA and protein in KGN cells treated with 60 μmol/L phosphoramide nitrogen mustard were significantly higher than those in the 0 μmol/L phosphoramide nitrogen mustard group (all P<0.001), while the levels of bcl2 mRNA and protein were significantly higher than those in the 0 μmol/L phosphoramide nitrogen mustard group ( P=0.005, P<0.001). The apoptosis rate of KGN cells after 60 μmol/L phosphoramide nitrogen mustard intervention was (38.10±2.90)%, while the apoptosis rate of KGN cells after 30 μmol/L phosphoramide nitrogen mustard intervention was (16.75±2.55)%, they were all significantly higher than that of the 0 μmol/L phosphoramide nitrogen mustard intervention group ( P=0.020, P=0.006). Hsa-miR-21-5p was transiently transfected into human umbilical cord blood mesenchymal stem cells, and the expression of has-miR-21-5p was higher than that in control group detected by qPCR ( P<0.001). The positive rate of surface protein CD9, CD63 and CD81 was 14.9%, 16.4% and 31.4%. The exosome was observed as "tea tray" or "concave hemisphere" by electron microscope. The exosome labeled by PKH-26 entered the granular cells and exerted biological effects. There was no statistically significant difference in bax mRNA expression levels between the 5 μg/mL, 10 μg/mL, and 15 μg/mL empty plasmid exosomes groups and the 60 μmol/L phosphoramide nitrogen mustard group (all P>0.05). However, the expression levels of bax mRNA in the 5 μg/mL, 10 μg/mL, and 15 μg/mL miR-21-5-p exosomes groups were lower than those in the 60 μmol/L phosphoramide nitrogen mustard group ( P=0.008, P=0.003, P<0.001). However, there was no statistically significant difference in the expression of bcl2 mRNA among the groups (all P>0.05). From the perspective of protein levels, there was no statistically significant difference in BAX protein expression between the 5 μg/mL, 10 μg/mL, and 15 μg/mL empty exosomes groups and 60 μmol/L phosphoramide nitrogen mustard group (all P>0.05), while the 5 μg/mL, 10 μg/mL, and 15 μg/mL miR-21-5-p exosomes groups showed a decrease in BAX protein expression compared with the 60 μmol/L phosphoramide nitrogen mustard group, and the differences were statistically significant (all P<0.001). However, there was no statistically significant difference in the expression of BCL2 protein among the intervention groups (all P>0.05). Conclusion:Hsa-miR-21-5p exosomes derived from human umbilical cord blood mesenchymal stem cells can effectively exert the anti-apoptotic effect.

Objective:To explore the effects of miR-21-5p exosomes derived from human umbilical cord mesenchymal stem cells on apoptosis of human granular cells.Methods:A granular cell apoptosis model was constructed by treating KGN cells with different concentrations (0 μmol/L, 30 μmol/L, 60 μmol/L, and 100 μmol/L) of phosphoramide nitrogen mustard for 48 h. The mRNA and protein levels of bax and bcl2 were detected using qPCR and Western blotting, respectively. The apoptosis rate was measured using flow cytometry to screen for the optimal concentration of phosphoramide nitrogen mustard for constructing an apoptosis model. Hsa-miR-21-5p overexpression plasmid was used for instantaneously transfecting human umbilical cord mesenchymal stem cells, and the expression level of hsa-miR-21-5p was detected by qPCR. The miR-21-5p exosomes were separated and identified by flow cytometry and electron microscope. Different concentrations (5 μg/mL, 10 μg/mL and 15 μg/mL) of miR-21 exosomes were added into successful KGN cell apoptosis model to overexpress miR-21. The mRNA and protein levels of bax and bcl2 were detected using qPCR and Western blotting, respectively. PKH-26 was used to trace the position of human granular cells. Results:The levels of bax mRNA and protein in KGN cells treated with 60 μmol/L phosphoramide nitrogen mustard were significantly higher than those in the 0 μmol/L phosphoramide nitrogen mustard group (all P<0.001), while the levels of bcl2 mRNA and protein were significantly higher than those in the 0 μmol/L phosphoramide nitrogen mustard group ( P=0.005, P<0.001). The apoptosis rate of KGN cells after 60 μmol/L phosphoramide nitrogen mustard intervention was (38.10±2.90)%, while the apoptosis rate of KGN cells after 30 μmol/L phosphoramide nitrogen mustard intervention was (16.75±2.55)%, they were all significantly higher than that of the 0 μmol/L phosphoramide nitrogen mustard intervention group ( P=0.020, P=0.006). Hsa-miR-21-5p was transiently transfected into human umbilical cord blood mesenchymal stem cells, and the expression of has-miR-21-5p was higher than that in control group detected by qPCR ( P<0.001). The positive rate of surface protein CD9, CD63 and CD81 was 14.9%, 16.4% and 31.4%. The exosome was observed as "tea tray" or "concave hemisphere" by electron microscope. The exosome labeled by PKH-26 entered the granular cells and exerted biological effects. There was no statistically significant difference in bax mRNA expression levels between the 5 μg/mL, 10 μg/mL, and 15 μg/mL empty plasmid exosomes groups and the 60 μmol/L phosphoramide nitrogen mustard group (all P>0.05). However, the expression levels of bax mRNA in the 5 μg/mL, 10 μg/mL, and 15 μg/mL miR-21-5-p exosomes groups were lower than those in the 60 μmol/L phosphoramide nitrogen mustard group ( P=0.008, P=0.003, P<0.001). However, there was no statistically significant difference in the expression of bcl2 mRNA among the groups (all P>0.05). From the perspective of protein levels, there was no statistically significant difference in BAX protein expression between the 5 μg/mL, 10 μg/mL, and 15 μg/mL empty exosomes groups and 60 μmol/L phosphoramide nitrogen mustard group (all P>0.05), while the 5 μg/mL, 10 μg/mL, and 15 μg/mL miR-21-5-p exosomes groups showed a decrease in BAX protein expression compared with the 60 μmol/L phosphoramide nitrogen mustard group, and the differences were statistically significant (all P<0.001). However, there was no statistically significant difference in the expression of BCL2 protein among the intervention groups (all P>0.05). Conclusion:Hsa-miR-21-5p exosomes derived from human umbilical cord blood mesenchymal stem cells can effectively exert the anti-apoptotic effect.

Cyclodipeptide (CDP) composed of two amino acids is the simplest cyclic peptide. These two amino acids form a typical diketopiperazine (DKP) ring by linking each other with peptide bonds. This characteristic stable ring skeleton is the foundation of CDP to display extensive and excellent bioactivities, which is beneficial for CDPs' pharmaceutical research and development. The natural CDP products are well isolated from actinomycetes. These bacteria can synthesize DKP backbones with nonribosomal peptide synthetase (NRPS) or cyclodipeptide synthase (CDPS). Moreover, actinomycetes could produce a variety of CDPs through different enzymatic modification. The presence of these abundant and diversified catalysis indicates that actinomycetes are promising microbial resource for exploring CDPs. This review summarized the pathways for DKP backbones biosynthesis and their post-modification mechanism in actinomycetes. The aim of this review was to accelerate the genome mining of CDPs and their isolation, purification and structure identification, and to facilitate revealing the biosynthesis mechanism of novel CDPs as well as their synthetic biology design.
Actinobacteria/metabolism* ; Actinomyces/metabolism* ; Biological Products/metabolism* ; Bacteria/metabolism* ; Diketopiperazines/metabolism* ; Amino Acids

Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.

Objective:To analyze of the main influecing factors of mosic embryos during the preimplantation genetic test for chromosomal structural rearrangement (PGT-SR) to avoid the increase of risk of abortion and genetic abnormalities and to improve the diagnostic rate of mosic embryos.Methods:We used a retrospective cohort study to analyze 94 cycles of infertile patients undergoing PGT-SR and 551 cycles of intracytoplasmic sperm injection (ICSI) from January 2018 to December 2019 in the Reproductive Medical Center of the Maternal and Child Health Hospital. The relationship of mosic embryos was analyzed between the age, the number of oocytes, gonadotropin (Gn)/oocyte, the grade of blastocysts and chromosome carrier of different genders by the SPSS21.0 software.Results:In the PGT-SR cycle, single factor analysis found that mosaic embryos were related to age and sperm concentration ( P=0.02, P=0.04), but multivariate logistic regression analysis showed that age ( OR=3.41, 95% CI=1.34-8.66, P=0.01), sperm concentration ( OR=0.41, 95% CI=0.17-0.96, P=0.04) and chromosome carrier of different genders ( OR=2.21, 95% CI=1.04-4.70, P=0.04) were the main factors of embryo mosaicism. Conclusion:Female age, sperm concentration and chromosome carrier of different genders maybe affect the formation of mosaic embryos, providing theoretical basis for selective transfer of mosaic embryos.