Cognition is a process in which the human brain receives external information, processes it, and transforms it into internal psychological activities to obtain or apply knowledge. Cognitive impairment is the impairment of one or more functions in memory, language, visual space, execution, calculation, and understanding, affecting an individual's daily or social ability. With the aging of the population, the incidence rate of cognitive impairment is increasing. Currently, biomarkers related to the cognitive impairment have become a research focus. Gut microbiota has emerged as a potential player in pathophysiology of cognitive impairment. Trimethylamine N-oxide (TMAO), the metabolite produced by gut microbiota, has mechanistic relevance to cognitive impairment. Therefore, the main goal of the present review is to provide the reader with potential mechanisms of TMAO and cognitive impairment. Although a link between TMAO and cognitive impairment is far from definitive, this review will serve as a call for research into this new area.

Objective To investigate the effect of exposure to bisphenol A (BPA) on maturation and oxidative stress injury in mouse oocytes in vitro. Methods Oocytes from female ICR mice were randomly divided into control group, DMSO group,and BPA group. Mouse oocytes in control group was cultured normorly in vitro,while added 0.1% DMSO in DMSO group, and 45 μmol/L BPA in 0.1% DMSO in BPA group. MII oocytes and oocytes stagnated in the GV phase were obtained .The levels of ROS in MII and GV oocytes of each group was detected by kit. The expression level of antioxidant enzyme in MII and GV oocytes was detected by immunofluorescence and Western blotting. Results Compared with control group, exposure to 45 μmol/L BPA during in vitro maturation, resulted in a significant decrease in the maturation rate of mouse oocytes in BPA group (26.32%±1.12%vs. 98.22%±0.89%, P<0.05), the levels of ROS in GV and MII oocytes were significantly higher (P<0.05), the levels of antioxidant enzymes CAT and SOD2 in GV and MII oocytes were significantly decreased (P<0.05). Conclusion Exposure to 45 μmol/L BPA increased ROS production and inhibited antioxidant enzyme expression, leading to oxidative stress damage of mouse oocytes and thus inhibiting oocyte maturation in vitro.

Objective To identify the high-risk factors and establish a nomogram for evaluating significant histological response (SHR) in chronic hepatitis B (CHB) patients receiving entecavir treatment. Methods Treatment-naive CHB patients who were presented to 14 hospitals, from October 2013 to October 2014, were enrolled and treated with entecavir for 72 weeks,prospectively. All the patients who underwent paired biopsies at treatment baseline and week 72 were analyzed. According to whether SHR (Ishak fibrosis score F≤2 points and histology activity index HAI≤4 points) was obtained during treatment, they were assigned to response group (n=160) and non-response group (n=567). High-risk factors were identified by multivariate logistic regression, and then were incorporated into a nomogram model. The discrimination, calibration and clinical applicability of nomogram were assessed by concordance index (C-index), calibration curve and clinical decision curve (DCA). Results After 72 weeks of treatment, regression of fibrosis, improvement of inflammation, virologic response, alanine aminotransferase (ALT)normalization and HBeAg seroconversion were 51.2%, 74.4%, 86.0%, 83.5% and 13.3%, respectively, however, 49.0% (306/625) of patients with virological response and 43.4% (165/380) of patients with ALT normalization did not achieved regression of fibrosis.Logistic regression analysis showed that baseline age (OR=0.978, 95%CI 0.958-0.998, P=0.030), platelet (PLT) (OR=1.005, 95%CI 1.001-1.010, P=0.030), liver stiffness measurement (LSM) (OR=0.931, 95%CI 0.892-0.972, P=0.001) and 72-week ALT (OR=0.980,95%CI 0.964-0.996, P=0.016), 72-week LSM (OR=0.858, 95%CI 0.782-0.941, P=0.001) were independent high-risk factors associated with SHR. The C-index of the nomogram model based on the above factors was 0.784, which was significantly better than 72-week AST/PLT ratio (APRI) (0.643), fibrosis-4 (FIB-4) (0.691) and LSM (0.735) alone, and had well-fitted calibration curves and DCA. Conclusions Incorporating baseline age, PLT, LSM, 72-week ALT and 72-week LSM, the established individualized nomogram model for evaluating significant histological response in CHB patients receiving antiviral therapy has good predictive performance and can reduce the need of liver biopsy.

Objective To explore the effect of miR-378a overexpression in modifying bone marrow mesenchymal stem cells (BMMSCs) combined with collagen sponge (CS) scaffold in repairing femoral defects of rats. Methods The BMMSCs were isolated and cultured, and the cell phenotype was identified by flow cytometry. The BMMSCs were transfected with an overexpressed miR-378a lentivirus and a negative unloaded lentivirus, and the transfected cells were divided into three groups: a BMMSCs transfected with overexpressed miR-378a group (LV-miR-378a group), BMMSCs transfected with negative control lentivirus group (LV-miR-NC group) and an untransfected BMMSCs group (control group). The transfection efficiency was detected by flow cytometry. The composite of transfected cells with CS scaffold was prepared, and the compatibility of the cells with the scaffold was observed by scanning electron microscopy. A femoral defect replantation model was established in SD rats, and 15 SD rats were randomly divided into three groups (n=5): LV-miR-378a+CS group (with the lentivirus complex CS scaffold overexpressing miR-378a implanted), LV-miR-NC+CS group (with the BMMSCs complex CS scaffold transfected with negative non-load lentivirus),and CS group (with the CS scaffold implanted only). At the 8th week after operation, the SD rats were sacrificed by CO₂ inhalation.The femur on the operation side was taken for gross observation and micro-CT scanning reconstruction. Bone mineral density(BMD) and bone volume/total volume (BV/TV) were quantified, and HE, Masson and osteopontin (OPN) immunohistochemical staining were used to observe bone repair. Results The phenotyping results of BMMSCs by flow cytometry showed that the positive expression rate of cell surface antigen CD44 and CD29 were 95.5% and 94.7%, respectively, while the positive expression rate of CD45 and CD34 were 0.8% and 0.7%, respectively. Transfection efficiency detected by flow cytometry: compared with the control group, the transfection efficiency of LV-miR-378a group and LV-miR-NC group increased obviously (P<0.05). The lentivirus transfection efficiency of LV-miR-378a group was consistent with that of LV-miR-NC group with no statistically significant difference (P>0.05). The results of scanning electron microscopy showed that the CS scaffold material had a good three-dimensional cavity structure. After the two groups of cells were co-cultured with the CS scaffold for 7 days, the cells in LV-miR-378a group had a larger spreading area on the surface of scaffold material than those in LV-miR-NC group, and the cells grow in clusters with more pseudopod. The gross observation results showed that the bone defect area in LV-miR-378a+CS group was completely repaired 8 weeks after surgery. The incompletely mineralized new bone could be observed in the bone defect centers of both LV-miR-NC+CS group and CS group, and the rough outline of the defect area could still be seen in CS group. The results of micro-CT three-dimensional reconstruction and quantitative analysis showed that 8 weeks after surgery, the repair effect of the bone defect area in LV-miR-378a+CS group was better than in other two groups, and there was more new bone deposition. The BMD and BV/TV values were significantly higher than those in other two groups (P<0.05). The defective areas in both LV-miR-NC+CS group and CS group were not completely repaired, and less new bone deposition and uneven density in CS group. HE and Masson staining results showed that the stent material in LV-miR-378a+CS group degraded completely 8 weeks after surgery, and more mature trabeculae could be seen, the junction area of new bone and host bone showed good continuity, and the trabeculae were connected with each other and had regular morphology. In LV-miR-NC+CS group, mature trabeculae were relatively few, and the junction area of new bone and host bone was not completely connected. In CS group, the stent materials were not completely degraded, and there were still more trabeculae in remodeling and irregular shape. Immunohistochemical staining showed that the expression rate of OPN in LV-miR-378a+CS group was significantly lower than that in other two groups 8 weeks after surgery, (P<0.05), and the expression rate of OPN in LV-miR-NC+CS group was lower than that in CS group (P<0.05). Conclusion Over-expression of miR-378a modified BMMSCs combined with CS scaffold can promote new bone formation.

Intestinal microorganisms are closely related to the pathogenesis of depression, but their specific mechanism of action has not been fully explained. Short-chain fatty acids (SCFA) are metabolites produced by the fermentation of plant polysaccharides, such as dietary fiber and resistant starch mediated by gut microorganisms, which are mainly composed of acetic acid, propionic acid, and butyric acid, and play an important role in the microbiota-intestine-brain axis. Recent studies have found that SCFA can not only regulate intestinal energy metabolism, but also improve depression through blood-brain barrier, immune pathway, endocrine pathway and vagus nerve. SCFA is the focus of scientific research nowadays, and there are few reports on SCFA intervention in depression in China. This article reviews the research progress of SCFA on depression, providing new ideas for clinical research.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by airway inflammation,lung tissue destruction and airflow limitation associated with airway remodeling. As an important form of cellular communication,extracellular vesicles (EVs) are capable of selectively transmitting signals to nearby or distant cells to regulate their function and phenotype, and thought to play an indispensable role in lung disease. EVs can be released by bronchial epithelial cells, lymphocytes,neutrophils, macrophages, vascular endothelial cells and mesenchymal stem cells upon activation or apoptosis under specific conditions. The role of EVs derived from these cells in the pathogenesis and progression of COPD is reviewed in present paper for contributing a more comprehensive and detailed understanding of the role of EVs in the complex pathophysiology of COPD.

Chronic hepatitis B virus infection is prevalent worldwide, and can progress to liver cirrhosis and even hepatocellular carcinoma if left untreated. Over the past 20 years, due to the approval and upgrading of nucleoside/nucleotide analogues, a qualitative leap has been made in inhibiting HBV replication. Most chronic hepatitis B (CHB) patients can achieve relief of hepatocellular inflammation, regression of hepatic fibrosis, improvement of life quality and survival time. With the extension of treatment time and the enrichment of treatment experience, new hot clinical issues gradually emerge, including the clinical application of new serum markers, the expansion of indicators for CHB antiviral treatment, the formation of CHB treatment plan and the improvement of long-term prognosis, which derserve further clinical attention.

Objective To investigate the effect and possible mechanism of the alcohol extract of Alisma orientalis on thyroid function of mother rats and neurological function of offspring with subclinical hypothyroidism (SCH). Methods A total of 85 female rats were selected, of which 15 rats acted as sham operation group and treated with sham operation, the other 70 rats underwent thyroidectomy + subcutaneous injection of levothyroxine (L-T₄) to establish the SCH model. Sixty-two of the 70 rats were successfully modeled, and randomly divided into low-dose Alisma ethanol extract group (15 rats, gavage with alcohol extract of Alisma orientalis 9 g/kg), high-dose Alisma ethanol extract group (16 rats, gavage with alcohol extract of Alisma 36 g/kg), L-T₄ group (16 rats, gavage with 4.5 μg/kg L-T₄), model group (15 rats, gavage with equal volume of normal saline), once a day, the intervention time is from 10th day of pregnancy (E10) to 21st day after birth (P21). The thyroid stimulating hormone (TSH) and thyroxine (T₄) of female rats at E17 were detected by electrochemiluminescence. ELISA was used to detect the nerve growth factor(NGF) and brain-derived neurotrophic factor (BDNF) in the hippocampus of offspring rats at P21; Western blotting was performed to detect the expression levels of tropomyosin receptor kinase A (TrkA), p-TrkA, c-AMP-response element binding protein (CREB)and p-CREB in the hippocampus of offspring rats at P21; The escape latency of pups at P40 was measured by the positioning cruise experiment, and the number of times the pups crossed the platform at P41 was measured by the space exploration experiment. Results At E17 gestational age, there was no significant difference in serum T₄ among the 5 groups of female mice (P>0.05). The serum TSH levels were lower in low- and high-dose Alisma ethanol extract group and L-T₄ group than that in model group, and the serum TSH levels were lower in high-dose Alisma ethanol extract group and L-T₄ group than that in low-dose Alisma ethanol extract group (P<0.05), while no significant difference existed in serum TSH levels between high-dose Alisma ethanol extract group and L-T₄ group (P>0.05). At P21, the NGF, BDNF, p-TrkA and p-CREB of hippocampus were significantly higher in low- and high-dose Alisma ethanol extract group and L-T₄ group than those in model group. The NGF, BDNF, p-TrkA and p-CREB were obviously higher in high-dose Alisma ethanol extract group and the hippocampus of L-T₄ group than those in the low-dose Alisma ethanol extract group (P<0.05). There was no statistically significant difference on NGF and BDNF between the high-dose Alisma ethanol extract group and the hippocampus of L-T₄ group (P>0.05). The escape latency of offspring rats was shorter in low- and high-dose Alisma ethanol extract group and L-T₄ group than that in model group, and the times of offspring crossing the platform were more than that in model group (P<0.05). The escape latency of offspring in the L-T₄ group was shorter than that in low-dose Alisma ethanol extract group, and the times of offspring crossing the platform was more than that in low-dose Alisma ethanol extract group(P<0.05). There was no significant difference in the escape latency and the times of crossing the platform between high-dose Alisma ethanol extract group and L-T₄ group (P>0.05). Conclusions The ethanol extract of Alisma orientalis applied to SCH mother rats can improve the thyroid function of the mother rats, promote the expression of neurological factors of offspring rats, and improve their learning and memory function. The mechanism may be related to the activation of the expression of TrkA signaling pathway.

Objective To analyze the clinical and pathological features of primary breast lymphoma (PBL) and explore the value of appling rituximab for the prognosis of patients with PBL. Methods The clinicopathological characteristics and therapeutic effect of rituximab were retrospectively analyzed of 65 patients with PBL admitted in the Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1, 2000 to January 31, 2020. According to different treatment methods,they were divided into CHOP group [n=41, using CHOP regimen (cyclophosphamide + epirubicin + vincristine + prednisone)] and RCHOP group (n=24, using rituximab combined CHOP regimen treatment). Patients received telephone follow-up or outpatient review until January 31, 2022 or mortality. Univariate regression analysis and multivariate regression analysis were used to analyze the factors influencing the prognosis of patients with PBL. Results All the 65 patients were female, aged 57(23, 86) years old.The tumor size was 2.8(0.4, 5.3) cm, and the follow-up time was 4.3(0.7, 21.8) years. There was a statistically significant difference in Ki-67 expression between the two groups (P=0.043), and there was no significant difference in other clinicopathological features and treatment plans (P>0.05). The 5- and 10-year overall survival rate of the 65 PBL patients were 93.4% and 87.9%,and the 5- and 10-year progression-free survival rate were 88.2% and 79.6%, the central nervous system recurrence rate was 4.6%.The 5-year overall survival rate in CHOP group was 93.8% and in RCHOP group was 92.9% (P=0.733), and 5-year progression-free survival rate was 89.9% in CHOP group, and in RCHOP group was 92.9% (P=0.897). Multivariate logistic regression analysis showed the international prognostic index (IPI) score and the level of β₂ microglobulin were the independent risk factors of overall survival (P<0.05). Conclusions There is no special clinical manifestation of PBL. The definite diagnosis mainly depends on histopathological examination and immunophenotype. Radical surgical resection can not improve the prognosis of patients, and comprehensive treatment based on full-term chemotherapy should be adopted; whether patients with PBL received rituximab was not associated with the survival benefits.

Objective To investigate the effects of hepatitis B virus (HBV) and liver function status on the occurrence and development of gestational diabetes mellitus (GDM). Methods The medical data of 628 pregnant women, who underwent prenatal examination and delivery in Chongqing Health Center for Women and Children from January 2018 to October 2021, were collected and retrospectively analyzed. Depending on whether infected with HBV, the patients were divided into HBV positive group(n=389) and HBV negative group (n=239). Those in HBV positive group were then further divided into normal liver function group(n=301) and abnormal liver function group (n=88) according to the liver function status in the second trimester of pregnancy so as to analyze the influence of HBV infection and liver function status on the occurrence and development of GDM. A total of 137 pregnant women who met the diagnostic criteria of GDM were divided into HBV positive group (n=97) and HBV negative group(n=40) according to the different HBV infection status. Those in HBV positive group were then divided into normal liver function group (n=62) and abnormal liver function group (n=35) according to their liver function status in the second trimester, so as to analyze the influence of HBV infection on blood glucose and postpartum blood glucose in GDM patients and adverse pregnancy outcomes. Results The fluctuation of blood glucose levels of pregnancy OGTT 1 h and 2 h was more obvious in pregnant women with positive HBV infection than those in negative group of HBV infection (P<0.05). The incidence of GDM was increased (24.9%vs. 16.7%) and gestational age was shortened in the pregnant women with positive HBV infection (P<0.05). Among the pregnant women with positive HBV infection, the average age, fasting blood glucose in the second trimester, OGTT 1 h, 2 h blood glucose and the incidence of GDM were higher in those with abnormal liver function (39.8% vs. 20.1%) than in those with normal liver function (P<0.05). HBV-infected GDM pregnant women with abnormal liver function developed higher blood glucose level in the second trimester of pregnancy, fasting blood glucose level within 6-12 weeks postpartum and a higher risk of impaired glucose tolerance than those with normal liver function (P<0.05). The incidence of GDM in the second pregnancy of pregnant women with HBV infection was higher than those in the first pregnancy (P<0.05). The rate of cesarean section and postpartum hemorrhage was higher in GDM with HBV infection pregnant women than those GDM pregnant women with normal liver function (P<0.05). Conclusions HBV infection with liver function damage can increase the incidence of GDM. GDM patients with HBV infection and liver function damage have a higher risk of adverse pregnancy outcomes. HBV infection may prolong the recovery time of postpartum blood glucose metabolism in pregnant women.