Objective To explore the biological effects and changes of metabolites of Guilu erxian glue(GLE)in vivo in the pre-vention and treatment of postmenopausal osteoporosis(PMO),based on non-targeted metabolomics.Methods Fifty SD female rats were divided into five groups using the random number table method:sham group,model group(OVX),and low-,medium-,and high-dose GLE(GLE-L,GLE-M and GLE-H)groups,with ten mice in each group.After 1 week of modeling,the drug was given by gavage,and samples were collected 8 weeks later.Bone microstructure was detected by MicroCT,bone metabolism-related indices were analyzed by immunohistochemistry(IHC),and a serum metabolite atlas was constructed using the LC-MS/MS technique to observe the distribution differences of metabolites and related pathways.Results The MicroCT results showed that GLE could increase the percentage of bone trabeculae and restore bone microstructure(P<0.05,GLE-M group vs.OVX group).IHC analysis showed that GLE could increase Runx2 expression in femur(P<0.05,GLE-M group vs.OVX group).There were four co-regulated metabolites in the sham group,GLE-H group,and OVX group,including 3-(3-methoxyphenyl)propionic acid,acetamide,Equol,and 1-oleoacyl-SN-glycerol-3-phosphocholine,which showed high expression in the sham group,low expression in the OVX group,and high expression in the GLE-M group.The KEGG pathway result showed that the main pathways involved between the sham group and OVX group were steroid hormone biosynthesis and cortisol synthesis and secretion.Tryptophan metabolism and phenylalanine metabolism were observed in the GLE group and OVX group.Conclusion GLE may prevent PMO by regulating metabolites in the body.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective To explore the biological effects and changes of metabolites of Guilu erxian glue(GLE)in vivo in the pre-vention and treatment of postmenopausal osteoporosis(PMO),based on non-targeted metabolomics.Methods Fifty SD female rats were divided into five groups using the random number table method:sham group,model group(OVX),and low-,medium-,and high-dose GLE(GLE-L,GLE-M and GLE-H)groups,with ten mice in each group.After 1 week of modeling,the drug was given by gavage,and samples were collected 8 weeks later.Bone microstructure was detected by MicroCT,bone metabolism-related indices were analyzed by immunohistochemistry(IHC),and a serum metabolite atlas was constructed using the LC-MS/MS technique to observe the distribution differences of metabolites and related pathways.Results The MicroCT results showed that GLE could increase the percentage of bone trabeculae and restore bone microstructure(P<0.05,GLE-M group vs.OVX group).IHC analysis showed that GLE could increase Runx2 expression in femur(P<0.05,GLE-M group vs.OVX group).There were four co-regulated metabolites in the sham group,GLE-H group,and OVX group,including 3-(3-methoxyphenyl)propionic acid,acetamide,Equol,and 1-oleoacyl-SN-glycerol-3-phosphocholine,which showed high expression in the sham group,low expression in the OVX group,and high expression in the GLE-M group.The KEGG pathway result showed that the main pathways involved between the sham group and OVX group were steroid hormone biosynthesis and cortisol synthesis and secretion.Tryptophan metabolism and phenylalanine metabolism were observed in the GLE group and OVX group.Conclusion GLE may prevent PMO by regulating metabolites in the body.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the biocompatibility of new gadolinium-doped hydroxyapatite(Gd-HA)composite scaffolds and to explore their feasibility as cell culture materials and bone tissue engineering scaffolds.Methods The Gd-HA composite scaffolds were chemically synthesized and placed under the electron microscope for observation.The experiment was divided into three groups,the HA group,the Gd-HA group,and the control group.Rabbit adipose-derived mesenchymal stem cells(ADSCs)were isolated,cultured and characterized,and the Gd-HA composite scaffold extract was added to the ADSCs in vitro culture system.Cell survival and cytotoxicity were assessed by live-dead cell staining,cell proliferation ability within the scaffolds was assessed by CCK-8 assay,and the scaffolds were assessed by alizarin red staining for cell osteogenic differentiation.The toxic reactions of the scaffold materials were observed by skin irritation test,systemic acute toxicity test and muscle tissue and liver and kidney pathology at the site of intramuscular implantation of the scaffolds.Results The Gd-HA composite scaffold showed irregular void structure under electron microscope.Cell morphology observation showed that ADSCs grew adherently to the wall and were long shuttle-shaped.The positivity rate of CD29 was 96.94％,CD44 was 97.90％,CD45 was 0.10％,and CD34 was 0.46％,which was obtained using flow cytometry.Live-dead cell staining showed that the amount of live cells in the Gd-HA group was significantly better than that in the hydroxyapatite(HA)group after 5 days of co-culture.CCK-8 assay showed no significant difference in cell proliferation within 0-3 days.After 3 days,the Gd-HA group was significantly better than the HA group and the control group(P＜0.05).Calcium nodule deposition after alizarin red staining was significantly better in the Gd-HA group than in the HA and control groups,showing a deeper red color.No skin irritation was observed in gross and skin tissue HE observations after the contact of the extract with the skin.The general condition of the experimental groups was good after the infusion of the extract into the abdominal cavity,and the body mass tended to increase steadily(P＞0.05).HE staining showed that inflammatory reaction at the interface between the material and muscle tissue of the stent intramuscular implantation site in Gd-HA group was significantly higher than that of the control group,and the inflammatory cell infiltration was gradually reduced with the prolongation of implantation time.At the 8th weeks the morphology of the tissue around the material was close to normal muscle tissue,and no pathological changes were observed in the HE staining of liver and kidney at the 12th week.Conclusion Gd-HA composite scaffolds exhibit good biocompatibility and facilitate cell proliferation and osteogenic differentiation,and they are expected to serve as good carriers for stem cell transplantation in tissue engineering.

Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objective:To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value.Methods:Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31 st, 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the β coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results:Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P<0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis ( P>0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation ( t=-30.39, P<0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions:Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis