In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
COVID-19 ; Cohort Studies ; Hepatitis B, Chronic/epidemiology* ; Humans ; Retrospective Studies ; Risk Factors

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Abstract: Objective　To analyze the survival status of HIV/AIDS patients aged above 50 years receiving antiviral therapy (ART) in Shanxi Province from 2011 to 2019, and to provide evidence for further improvement of antiviral therapy. Methods　Basic information and follow-up information of HIV/AIDS patients aged above 50 years who first received HIV/AIDS antiviral therapy in Shanxi Province from 2011 to 2019 were collected. Excel database was established and SPSS23.0 software was used for analysis. Retrospective cohort study was conducted. Cox proportional risk regression model was used to analyze the factors influencing survival time. Results　A total of 1 183 subjects were included, of which 172 died, including 84(48.84%) from other causes, 74(43.02%) AIDS-related death and 14 (8.14%) from accidents, suicides and undetermined deaths. Setting AIDS-related deaths as an outcome event, life table analysis showed that the cumulative survival rates at 1, 3, 5, 7 and 9 years after receiving ART were 96.61%, 93.59%, 90.35%, 87.57% and 83.44%, respectively. Multivariate Cox proportional risk model analysis showed that the risk of death in patients aged 60-<70 years group and over 70 age group was 2.53 times (95%CI: 1.51-4.23) and 3.59 times (95%CI: 1.74-7.40) for patients aged the 50-<60 group , respectively. The risk of death in patients with baseline CD4+T lymphocyte (CD4) counts of ≥200/mm3, 50-<200 /mm3 was 0.22 times (95%CI: 0.12-0.41) and 0.37 times (95%CI: 0.21-0.67) for patients with CD4+T lymphocyte counts of <50/mm3. The risk of death in patients with opportunistic infections at baseline was 1.99 times (95%CI: 1.16-3.39) for patients without baseline opportunistic infections. Conclusions　The survival rate of HIV/AIDS patients aged above 50 who received antiviral therapy (ART) in Shanxi Province from 2011 to 2019 was relatively high. To further improve the quality of antiviral treatment in our province, the strategy of "early detection and early treatment" should be continued and improved in the future, and information collection of specific causes of non-AIDS-related deaths among this population should be further strengthened.

We used metabolomics to investigate the ability of a traditional Mongolian medicine called modified Tabusen-2 (MT-2) to improve kidney yang deficiency (KYD) in rats. All animal experiments were conducted under the guidance and standards of the Medical Ethics Committee of Inner Mongolia Medical University. SD rats were divided into 6 groups of six rats: a normal group, a model group, Jinkuishenqi pill administration group (1.26 g·kg^-1), and MT-2 administration in high-, medium- and low-dose groups (1.512, 0.756, and 0.378 g·kg^-1). KYD was established by intramuscular injection of hydrocortisone (HC) and biochemical indicators and clinical characterization was used to confirm that KYD was established. All groups received intragastrically administered drug (Jinkuishenqi pill or MT-2) or saline. Serum from each group was collected after 8 weeks and analyzed by UPLC-Q-exactive-MS to measure various biochemical indicators. The biomarkers affected by MT-2 were identified and the metabolic pathways of KYD regulated by MT-2 were analyzed by metabolomic analysis. The results show that MT-2 can decrease serum creatinine (Cr) in KYD rats and significantly increase (P<0.05) the content of thyroid stimulating hormone (TSH) and luteinizing hormone (LH). In serum samples, 38 biomarkers such as corticosterone, L-phenylalanine, and DL-tryptophan were measured as possible indicators for disease development in KYD rats. MT-2 lowered 18 biomarkers of KYD, including corticosterone, deoxycorticosterone, and L-phenylalanine, and altered 13 related metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and steroid hormone biosynthesis, resulting in an overall improvement in KYD. MT-2 appears to be important in improving KYD in rats mainly by regulating metabolites such as amino acids, steroids and lipids.

Background Aluminum (Al) can cause irreversible damage to neurons and synapses function, and the mechanism may be connected to mitochondrial damage caused by glycogen synthase kinase-3β (GSK-3β) regulating dynamin-related protein 1 (DRP1), resulting in inhibition of the growth of neuronal protrusions. Objective To investigate the role of GSK-3β regulating DRP1 in the inhibition of primary hippocampal neurite growth induced by Al. Methods Neurons were extracted from the hippocampus of newborn mice (≤24 h old) for primary culture. On day 6, the purity of neurons was detected by immunofluorescence. On day 10, neurons with good growth state were selected for Al exposure and GSK-3β inhibitor SB216763 (SB) intervention. The experiment design included a blank control group, a dimethyl sulfoxide (DMSO) group, an Al (20 μmol·L⁻¹) group, a SB (1 μmol·L⁻¹) group, and a SB (1 μmol·L⁻¹) + Al (20 μmol·L⁻¹) group. After primary hippocampal neurons were treated with Al or SB for 48 h, cell viability was detected by CCK-8 assay, the mitochondrial morphology of primary hippocampal neurons was observed by transmission electron microscopy, the total protrusion length of primary hippocampal neurons was scanned and analyzed by laser confocal imaging, and their complexity was analyzed by Sholl analysis. The expression levels of phospho-GSK-3β, GSK-3β, and DRP1 were detected by Western blotting. Results The immunofluorescent results showed that the purity of primary neurons was higher than 90%. After the Al exposure and the SB intervention for 48 h, compared with the blank control group, there was no obvious difference in cell viability in the DMSO group and the SB group (P>0.05), and the Al group showed reduced cell viability (P=0.006); there was no obvious difference in cell viability between the SB+Al group and the Al group (P>0.05). Compared with the blank control group, there was no obvious difference in the average total length of protrusion in the DMSO group and the SB group (P>0.05), and the Al group showed reduced average total length of neurite (P<0.001); the average total neurite length in the SB+Al group was significantly increased compared with that in the Al group (P=0.001). The results of Sholl analysis revealed that, within 130 μm from the cytosol, the number of intersections of neurons in each group increased with the increase of distance. Above 130 μm from the cytosol, the number of intersections of neurons in each group decreased gradually with increase of distance. At 130 μm and 310 μm from the cytosol, compared with the blank control group, the number of neuronal intersections in the DMSO group and the SB group had no obvious difference (P>0.05), and that in the Al group was significantly reduced (P<0.05); there was no obvious difference in the number of neuronal intersections between the SB+Al group and the Al group (P>0.05). The mitochondrial structure of the blank control group was complete and the crest was clearly visible; there was no apparent variation in the mitochondrial structure in the DMSO group and the SB group; the mitochondria in the Al group were vacuolated and the crista disappeared; the SB+Al group showed clearer crista than the Al group. The difference in GSK-3β phosphorylation level among groups was statistically significant (F=45.841, P<0.001). Compared with the blank control group, the GSK-3β phosphorylation level showed not significantly different in the DMSO group (P>0.05), increased in the SB group (P=0.022), and significantly reduced in the Al group (P<0.001); the GSK-3β phosphorylation level was significantly higher in the SB+Al group than in the Al group (P<0.001). The difference in DRP1 protein level among groups was statistically significant (F=8.389, P=0.003). Compared with the blank control group, the DRP1 protein levels in the DMSO group and the SB group were not significantly different (P>0.05), and significantly increased in the Al group (P=0.001); the DRP1 protein level in the SB+Al group was significantly lower than that in the Al group (P=0.029). Conclusion Al may increase the level of DRP1 protein by activating GSK-3β, causing mitochondrial damage and inhibiting neuronal protrusions growth.

OBJECTIVE: To investigate the significance and distribution of oxidized low-density lipoprotein antibodies (ox-LDL-Ab) in patients with antiphospholipid syndrome (APS). METHODS: In this study, 334 patients who were hospitalized in the Department of Rheumatology and Immunology, Peking University People's Hospital were included. There were 162 APS patients, 122 patients with other autoimmune diseases without thrombosis or obstetric disease as disease control and 50 healthy controls. The clinical data and laboratory indicators were retrospectively collected. The ox-LDL-Ab, anticardiolipin (aCL) IgG/IgA/IgM, and anti-β2-glycoprotein Ⅰ (aβ2GPI) IgG/IgA/IgM were detected by enzyme-linked immunosorbent assay (ELISA). The relationship between ox-LDL-Ab and clinical and laboratory parameters were analyzed by SPSS 27.0. RESULTS: In APS group, 60.5% of patients had thrombosis, 48.1% had pregnancy morbidity, 34.0% had thrombocytopenia. The positive rates of aCL, aβ2GPI and lupus anticoagulant (LAC) were 17.9%, 34.6%, and 46.9%, respectively. The ox-LDL-Ab titers and positive rate in APS group were higher than that in healthy controls [titers: 40.8 (25.4-66.0) U/mL vs. 24.1 (12.3-36.5) U/mL, P=0.001; positive rate: 67.3% vs. 36.0%, P=0.001]. The diffe-rences in titers and positive rate of ox-LDL-Ab between APS patients and disease controls were not statistically significant [titers: 40.8 (25.4-66.0) U/mL vs. 35.9 (24.2-53.1) U/mL, P=0.118; positive rate: 67.3% vs. 61.5%, P=0.318]. The area under curve (AUC) for aβ2GPI, aCL, and ox-LDL-Ab were 0.745 (95%CI: 0.692-0.797), 0.666 (95%CI: 0.608-0.724), 0.609 (95%CI: 0.549-0.669), respectively. The Youden's index was 0.388, 0.269, and 0.132, respectively. The AUC for ox-LDL-Ab in seronegative APS patients was 0.562 (95%CI: 0.480-0.645). The sensitivity and specificity of ox-LDL-Ab in seronegative APS patients were 63.9% and 47.0%, respectively, and the Youden's index was 0.109. The ox-LDL-Ab positive group had higher positive rate of aβ2GPI (42.2% vs. 18.9%, P=0.003) and aCL (22.9% vs. 7.5%, P=0.017) than the ox-LDL-Ab negative group. There was no correlation between ox-LDL-Ab and thrombosis, coronary artery disease, pregnancy morbidity, hyperlipidemia, hypocomplementemia, and LAC positivity. CONCLUSION Ox-LDL-Ab was correlated with aCL and aβ2GPI, and no association were observed between ox-LDL-Ab and thrombosis, coronary artery disease, and pregnancy morbidity.
Pregnancy ; Female ; Humans ; Antiphospholipid Syndrome ; Antibodies, Anticardiolipin ; Retrospective Studies ; Coronary Artery Disease ; Clinical Relevance ; beta 2-Glycoprotein I ; Lupus Coagulation Inhibitor ; Lipoproteins, LDL ; Autoantibodies ; Immunoglobulin G ; Immunoglobulin A ; Thrombosis ; Immunoglobulin M