AIM:To investigate the protective effects of Dendrobium officinale polysaccharide(DOP)on high glucose-induced apoptosis in retinal capillary pericytes and its potential mechanism involving mitochondrial function.METHODS:Retinal capillary pericytes were allocated into five groups: normal control(NC), high glucose(HG), and three DOP treatment groups(low, DOP-L; medium, DOP-M; high, DOP-H). Pericyte ultrastructure was analyzed using transmission electron microscopy(TEM). Apoptotic rate was quantified via Annexin V-FITC staining. Mitochondrial transmembrane potential was assessed using the JC-1 probe. Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot were employed to measure expression levels of cytochrome C(Cyt C), B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), Caspase-9, and Caspase-3, respectively.RESULTS:Compared to the NC group, pericytes exposed to HG exhibited significant mitochondrial damage, elevated apoptotic rate, increased mRNA and protein expression of Cyt C, Bax, Caspase-9, and Caspase-3(all P<0.01), alongside a marked reduction in mitochondrial transmembrane potential and expression of Bcl-2 mRNA and protein(all P<0.01). In contrast, DOP treatment groups(DOP-M,DOP-H)dose-dependently ameliorated mitochondrial damage, reduced apoptotic rate, downregulated Cyt C, Bax, Caspase-9, and Caspase-3 expression, enhanced mitochondrial transmembrane potential, and upregulated Bcl-2 expression relative to the HG group(all P<0.05).CONCLUSION:DOP attenuates high glucose-induced apoptosis and mitochondrial injury in retinal capillary pericytes. The underlying mechanism may involve the restoration of mitochondrial transmembrane potential.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective:To investigate the use of targeted next generation sequencing (tNGS) for the detection of drug resistance in mycoplasma pneumoniae pneumonia (MPP) and analyze the clinical characteristics of MPP.Methods:The clinical data of patients with MPP who underwent bronchoalveolar lavage fluid tNGS at the Department of Respiratory and Critical Care Medicine, The Third People's Hospital of Hubei Province, Jianghan University from February 2022 to February 2024 were collected. According to inclusion and exclusion criteria, 80 patients with MPP were included in this study. The clinical data of the patients were retrospectively analyzed. tNGS of bronchoalveolar lavage fluid was performed to assess drug resistance in MPP. These patients were divided into a drug resistance group ( n = 55) and a non-drug resistance group ( n = 25) based on the presence or absence of the 23SrRNA:A2063G drug resistance mutation. Patient's clinical characteristics were compared between the two groups. The significant indicators from the univariate analysis were introduced into a binary logistic regression model to analyze the independent predictors of drug resistance and their predictive values. Results:The median age of patients with MPP was 38 years, with 53.75% (43/80) being female. Among the patients, 62.50% (50/80) had no underlying diseases, and 68.75% (55/80) exhibited drug resistance, while 42.50% (34/80) had mixed infections. The three most common clinical symptoms were cough (92.50%, 74/80), fever (62.50%, 50/80), and dyspnea (31.25%, 25/80). The most common imaging findings in MPP included patchy shadows (48.75%, 39/80) and consolidation shadows (42.50%, 34/80). Nodular shadows (7.50%, 6/80), tree-in-bud signs (5.00%, 4/80), ground-glass opacities (11.25%, 9/80), bronchial wall thickening (3.75%, 3/80), and pleural effusions (5.00%, 4/80) were not common. Bilateral lesions were present in 40.00% (32/80) of cases. In laboratory examinations, the median levels of inflammatory markers C-reactive protein (39.45 mg/L), procalcitonin (0.08 g/L), and serum amyloid A (168.31 mg/L) were increased. The median or mean levels of other indicators were within the normal range. There were no significant differences between the drug resistance and non-drug resistance groups in terms of gender, age, underlying diseases, clinical symptoms, length of hospital stay, mixed infection rate, mycoplasma pneumoniae (MP)-IgG positivity, MP-IgM level > 300 AU/mL, MP-DNA positivity, percentage of lymphocytes, platelet count, number of lymphocytes, and procalcitonin, D-dimer, prealbumin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and albumin levels as well as imaging findings (all P > 0.05). In the drug resistance group, the number of fever days, sequence number, white blood cell count, percentage of neutrophils, C-reactive protein level, and serum amyloid A level were as follows: 4 (0, 7), 24464.00 (2754.00, 43457.00), 7.35 (6.09, 9.84), 73.70 (67.20, 73.70), 39.82 (20.82, 70.40), and 205.40 (81.08, 338.30), respectively. These values were significantly higher than those in the non-drug resistance group [2 (0, 4.50), 658.00 (323.00, 7593.00), 6.12 (5.04, 7.20), 64.45 (58.58, 76.33), 35.63 (4.94, 57.36), 81.30 (12.51, 243.76), Z = -2.43, -4.67, -2.72, -2.36, -2.04, -2.37]. The albumin level in the drug resistance group was 41.50 (38.10, 44.30), which was significantly lower than that in the non-drug resistance group [43.55 (40.03, 46.05), Z = -2.07, P < 0.05]. In the binary logistic regression analysis, the sequence number was identified as an independent predictor of drug resistance. When the sequence number exceeded 1001, the area under the curve value was 0.827, with a sensitivity of 94.5% and specificity of 68.0%. Conclusions:The clinical manifestations of MPP are similar in both the macrolide-resistant and the non-resistant groups. However, the drug-resistant group exhibits a greater number of fever days, higher sequence numbers, and more severe inflammatory responses. The sequence number of MPP can be used to predict drug resistance. When the sequence number exceeds 1001, its predictive value for drug resistance is significantly higher.

Objective:To investigate the use of targeted next generation sequencing (tNGS) for the detection of drug resistance in mycoplasma pneumoniae pneumonia (MPP) and analyze the clinical characteristics of MPP.Methods:The clinical data of patients with MPP who underwent bronchoalveolar lavage fluid tNGS at the Department of Respiratory and Critical Care Medicine, The Third People's Hospital of Hubei Province, Jianghan University from February 2022 to February 2024 were collected. According to inclusion and exclusion criteria, 80 patients with MPP were included in this study. The clinical data of the patients were retrospectively analyzed. tNGS of bronchoalveolar lavage fluid was performed to assess drug resistance in MPP. These patients were divided into a drug resistance group ( n = 55) and a non-drug resistance group ( n = 25) based on the presence or absence of the 23SrRNA:A2063G drug resistance mutation. Patient's clinical characteristics were compared between the two groups. The significant indicators from the univariate analysis were introduced into a binary logistic regression model to analyze the independent predictors of drug resistance and their predictive values. Results:The median age of patients with MPP was 38 years, with 53.75% (43/80) being female. Among the patients, 62.50% (50/80) had no underlying diseases, and 68.75% (55/80) exhibited drug resistance, while 42.50% (34/80) had mixed infections. The three most common clinical symptoms were cough (92.50%, 74/80), fever (62.50%, 50/80), and dyspnea (31.25%, 25/80). The most common imaging findings in MPP included patchy shadows (48.75%, 39/80) and consolidation shadows (42.50%, 34/80). Nodular shadows (7.50%, 6/80), tree-in-bud signs (5.00%, 4/80), ground-glass opacities (11.25%, 9/80), bronchial wall thickening (3.75%, 3/80), and pleural effusions (5.00%, 4/80) were not common. Bilateral lesions were present in 40.00% (32/80) of cases. In laboratory examinations, the median levels of inflammatory markers C-reactive protein (39.45 mg/L), procalcitonin (0.08 g/L), and serum amyloid A (168.31 mg/L) were increased. The median or mean levels of other indicators were within the normal range. There were no significant differences between the drug resistance and non-drug resistance groups in terms of gender, age, underlying diseases, clinical symptoms, length of hospital stay, mixed infection rate, mycoplasma pneumoniae (MP)-IgG positivity, MP-IgM level > 300 AU/mL, MP-DNA positivity, percentage of lymphocytes, platelet count, number of lymphocytes, and procalcitonin, D-dimer, prealbumin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and albumin levels as well as imaging findings (all P > 0.05). In the drug resistance group, the number of fever days, sequence number, white blood cell count, percentage of neutrophils, C-reactive protein level, and serum amyloid A level were as follows: 4 (0, 7), 24464.00 (2754.00, 43457.00), 7.35 (6.09, 9.84), 73.70 (67.20, 73.70), 39.82 (20.82, 70.40), and 205.40 (81.08, 338.30), respectively. These values were significantly higher than those in the non-drug resistance group [2 (0, 4.50), 658.00 (323.00, 7593.00), 6.12 (5.04, 7.20), 64.45 (58.58, 76.33), 35.63 (4.94, 57.36), 81.30 (12.51, 243.76), Z = -2.43, -4.67, -2.72, -2.36, -2.04, -2.37]. The albumin level in the drug resistance group was 41.50 (38.10, 44.30), which was significantly lower than that in the non-drug resistance group [43.55 (40.03, 46.05), Z = -2.07, P < 0.05]. In the binary logistic regression analysis, the sequence number was identified as an independent predictor of drug resistance. When the sequence number exceeded 1001, the area under the curve value was 0.827, with a sensitivity of 94.5% and specificity of 68.0%. Conclusions:The clinical manifestations of MPP are similar in both the macrolide-resistant and the non-resistant groups. However, the drug-resistant group exhibits a greater number of fever days, higher sequence numbers, and more severe inflammatory responses. The sequence number of MPP can be used to predict drug resistance. When the sequence number exceeds 1001, its predictive value for drug resistance is significantly higher.

Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
Adult ; Female ; Humans ; Young Adult ; Epilepsy ; Hippocampus ; Memory, Short-Term ; Mental Recall ; Prefrontal Cortex ; Theta Rhythm ; Male

Objective:To analyze the nutritional status of elderly inpatients using Global Leadership Initiative on Malnutrition (GLIM) criteria.Methods:A total of 5 236 elderly patients (aged 65 years or older) who were hospitalized at the West China Hospital, Sichuan University from March 2021 to March 2022 were included. The nutritional status was analyzed using the GLIM diagnostic criteria for malnutrition.Results:The rate of patients at nutritional risk was 30.29%, and the incidence of malnutrition as per GLIM criteria was 15.64%. The levels of hemoglobin, albumin, triglycerides, and cholesterol, and body mass index of the malnutrition group were lower compared with the non-malnutrition group, and the differences were statistically significant ( P<0.05). The non-malnutrition group had significantly shorter hospital stay and lower hospitalization costs compared with the malnutrition group ( P<0.001). Conclusions:The GLIM criteria is suitable for evaluating the nutritional status in elderly inpatients. The incidence of malnutrition in elderly inpatients is relatively high, which deserves attention in clinical management.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.