In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans ; Cytomegalovirus Infections/virology* ; Wnt Signaling Pathway ; Pregnancy ; Female ; Cytomegalovirus/physiology* ; Pregnancy Complications, Infectious/virology* ; Congenital Abnormalities/virology* ; Animals

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

The anti-inflammatory efficacy of Callicarpa nudiflora extract were evaluated upon lipopolysaccharide (LPS)-induced infective inflammation in rats. Pathological changes of lung and colon tissues observed with hematoxylin-eosin (H&E) staining, together with inflammatory factors in serum, including nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were applied to assess the mitigating effects of C. nudiflora water extract on model rats. The experimental protocol strictly adhered to the guidelines of the Ethics Committee of Animal Research of Guangdong Pharmaceutical University (Approval: gdpulac2022132). Quality markers with anti-inflammatory activities were recognized by network pharmacology analysis. Subsequently, a reliable method for simultaneously quantifying six components was established. As a result, the pathological injury on lung and colon tissues of model rats induced by LPS were improved by C. nudiflora water extract. Compared with model group, C. nudiflora extract had decreased the release of proinflammatory factors in serum, including TNF-α and IL-6, and reduced the NO (P < 0.01). Network pharmacological analysis obtained 83 chemical components, 466 component targets, 584 disease targets and 129 action targets, which were mainly concentrated in 624 biological processes such as inflammatory response and positive regulation of nitric oxide biosynthesis, as well as 162 pathways such as phosphatidylinositol-3-hydroxykinase-protein kinase (PI3K-Akt) signal pathway and Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signal pathway. Upon analyzing their specificity, effectiveness, detectability, and quantity transfer rule from herb to extract, 6-hydroxyluteolin 7-glucoside, cynaroside, caffeic acid, acteoside, isoacteoside, and forsythoaside B were identified as the quality markers. Their anti-inflammatory activities were verified with LPS-induced inflammation model of RAW264.7 cells. Then contents of these 6 quality markers in 16 batches of C. nudiflora were determined. Thereby, the anti-inflammatory efficacy of C. nudiflora extract were confirmed in vivo, 6-hydroxyluteolin 7-glucoside, cynaroside, caffeic acid, acteoside, isoacteoside, and forsythoaside B were identified as anti-inflammatory ingredients, which can be used as quality control indicators for the herb and related formulation.