In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

In recent years, the incidence of cerebral small vessel disease (CSVD) has been increasing with the aging of the population, and the cognitive impairment caused by it has brought huge burden to patients and their families. As a novel inflammatory biomarker, lipoprotein-associated phospholipase A 2 (Lp-PLA 2) directly participates in the pathogenesis of cognitive impairment in patients with CSVD by regulating circulatory vascular injury and neuroinflammation, and is expected to become a predictive indicator and therapeutic target for CSVD.

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Adult ; Humans ; Retrospective Studies ; Neoplasm, Residual/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Recurrence ; Leukemia, Myeloid, Acute/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To explore the risk intensity and related influencing factors of post-traumatic stress disorder (PTSD) among high-stress rescue workers, and to provide effective tools for the risk assessment of PTSD in military rescue workers. Method: From June to August 2022, cluster sampling was used to select the high-stress rescue personnel of an Army department as the survey subjects. The acute Stress reaction (ASD) scale and PTSD checklist were used to evaluate the risk of PTSD in military rescue personnel. Multivariate logistic regression were used to analyze the influencing factors of PTSD. Results: The age of 4 460 subjects was (24.38±4.072) years old, including 4 396 males (98.6%). The positive rate of initial screening for ASD was 2.85% (127/4 460). The positive rate of PTSD was 0.67% (30/4 460). Multivariate logistic regression model analysis showed that female, older age, recent trauma exposure history, passive smoking and alcohol consumption were at higher risk of ASD, the values of OR (95%CI) were 4.183 (1.819-9.618), 6.278 (1.363-28.912), 3.094 (1.500-6.379), 2.059 (1.298-3.267) and 2.607 (1.614-4.211), respectively; Lower education level was associated with lower risk of ASD, OR (95%CI) was 0.593 (0.359-0.978); People who are older, thinner, have a history of mental illness, and drink alcohol were at higher risk for PTSD, the values of OR (95%CI) were 20.144 (2.459-165.043), 10.287 (2.218-47.700), 91.104 (8.592-965.980) and 2.866 (1.144-7.180), respectively. Conclusion: Gender, age, education level, passive smoking, alcohol consumption, past history of mental illness and body mass index may be related to the potential risk of PTSD in rescue workers,passive smoking, alcohol consumption, and weight controlling should be focused on to reduce potential risks of PTSD.
Male ; Humans ; Female ; Young Adult ; Adult ; Stress Disorders, Post-Traumatic/prevention & control* ; Tobacco Smoke Pollution ; Risk Assessment ; Military Personnel ; Alcohol Drinking

Objective:Molecular biology experimental technology has become an important basic tool for exploring biology and medicine and other related disciplines. We aim to explore an effective molecular biology experimental teaching model which will definitely improve students' molecular biology experimental skills and autonomous learning ability.Methods:Guided by the theory of constructivism, with the molecular biology experimental course as the carrier, and with the basic requirements of constructing the basic molecular biology experimental technology of the system, a teaching platform was established to guide students to preview the experiment independently; the physical experimental projects were integrated and optimized and the virtual simulation experimental projects were increased, with virtuality and reality, to improve students' molecular biology experimental skills and autonomous learning ability.Results:An online teaching platform has been established, which effectively guides and improves the effect of students' preview experiments, and cultivates the ability of autonomous learning. Besides, the experimental teaching mode combining optimization of physical experimental projects and virtual simulation experimental projects significantly improved students' molecular biology experimental operation skills and problem-solving ability.Conclusion:A constructivism-based teaching mode of combining virtual and real molecular biology has been established, which is an effective way to improve students' molecular biology experimental skills and autonomous learning ability.

Autoimmune diseases of the nervous system are a group of diseases caused by the body′s immune system attacking its own nervous system, resulting in structural damage and functional impairment of the corresponding tissues. Interventional clearance of pathogenic auto-antibodies has been shown to be effective in reducing immune damage, inhibiting disease progression and improving prognosis through extensive basic research and long-term clinical practice. The neonatal Fc receptor (FcRn)-mediated circulating protection mechanism of IgG contributes to the long half-life and high plasma levels of IgG. FcRn inhibitors are able to target and block the binding of FcRn to IgG, accelerating IgG clearance and reducing IgG levels. Therefore, the use of FcRn inhibitors in the treatment of autoimmune diseases of the nervous system could theoretically help to accelerate the clearance of pathogenic IgG, achieve good clinical efficacy and have promising applications. Research in this area has made considerable progress in recent years and this article will review this.

Cerebral small vessel disease (CSVD) is a series of clinical syndrome characterized by the damage of small blood vessels in the brain caused by a variety of causes. Although the pathophysiological mechanisms of CSVD are not fully understood, increasing evidence suggests that matrix metalloproteinase-9 plays an important role in the occurrence and development of CSVD.

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median (Q₁, Q₃) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure (P<0.05). Each 2.71 μg/L (log-transformed) increase of the lead was associated with a 2.05 (95%CI: 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95%CI: 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95%CI: 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95%CI: 0.03, 0.29)×10⁹/L elevation in white blood cells, and 0.11 (95%CI: 0.02, 0.21)×10⁹/L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95%CI: 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95%CI: 1.11%, 7.10%) and 2.42% (95%CI: 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.
Adult ; Male ; Humans ; Blood Pressure/physiology* ; C-Reactive Protein/analysis* ; Lead ; Arsenic/analysis* ; Cadmium ; Biomarkers ; Hypertension/epidemiology* ; China/epidemiology*

Objective: To evaluate the association of lead exposure with stunting and underweight among children aged 3-5 years in China. Methods: Data was collected from China National Human Biomonitoring (CNHBM) between January 2017 and December 2018. A total of 3 554 children aged 3-5 years were included. Demographic characteristic, lifestyle and nutritional status were collected through questionnaires. Height and weight were measured by standardized method. Stunting and underweight status were determined by calculating height for age Z-score and weight for age Z-score. Blood and urine samples were collected to detect the concentrations of blood lead, urinary lead and urinary creatinine. Children were stratified into 4 groups (Q₁ to Q₄) by quartiles of blood lead level and corrected urinary lead level, respectively. Complex sampling logistic regression models were applied to evaluate the association of the blood lead level, urinary lead level with stunting and underweight. Results: Among 3 554 children, the age was (4.09±1.06) years, of which 1 779 (80.64%) were female and 1 948 (55.84%) were urban residents. The prevalence of stunting and wasting was 7.34% and 2.96%, respectively. The M (Q₁, Q₃) for blood lead levels and urinary lead levels in children was 17.49 (12.80, 24.71) μg/L, 1.20 (0.61, 2.14) μg/g Cr, respectively. After adjusting for confounding factors, compared with the lowest blood lead concentration group Q₁, the risk of stunting gradually increased in the Q₃ and Q₄ group (P_trend=0.010), with OR (95%CI) values of 1.40 (0.80-2.46) and 1.80 (1.07-3.04), respectively. Compared with the lowest urinary lead concentration group Q₁, the risk of stunting still increased in the Q₃ and Q₄ group (P_trend=0.012), with OR (95%CI) values of 1.69 (1.01-2.84) and 1.79 (1.05-3.06), respectively. The correlation between the lead exposure and underweight was not statistically significant (P>0.05). Conclusion: Lead exposure is positively associated with the risk of stunting among children aged 3-5 years in China.
Child ; Female ; Humans ; Infant ; Male ; Lead ; Thinness/epidemiology* ; Growth Disorders/epidemiology* ; Body Height ; Nutritional Status ; Prevalence ; China/epidemiology*

Objective: To investigate the dynamic expression pattern of carcinoembryonic Wnt3a and its early monitoring value using a hepatocellular carcinoma model. Methods: Forty-eight Sprague Dawley (SD) rats were fed with pellet feed containing 2-acetylaminofluorene (2-AAF, 0.05%) to induce hepatocarcinogenesis, and control rats were fed a pellet diet. Liver tissue and blood samples were collected every two weeks. Liver tissues were pathologically examined using HE staining and grouped. The gene and Wnt3a mRNA expression were analyzed by genome-wide microarray. The expression and distribution of Wnt3a in liver tissue were analyzed by immunohistochemistry. Wnt3a concentration in liver tissue and serum was quantified by enzyme-linked immunosorbent assay. Statistical methods such as χ² test, Mann-Whitney test and analysis of variance were used to analyze the differences between groups. Results: According to the pathological examination results, the rat livers were divided into four groups: control, hepatocyte degeneration, precancerous lesions and hepatocellular carcinoma. Genome-wide expression profiling analysis and comparison with the control group revealed that 268 and 312 genes were up-regulated and 57 and 201 genes were down-regulated in the precancerous and cancerous group when signal logarithm ratio (SLR) was >8 log₂^cy5/cy3, and these significantly altered genes mainly involved in cell proliferation, signal transduction, tumor metastasis, and apoptosis. The expression of Wnt3a at mRNA level was significantly increased in all stages of cancer induction, including degeneration group (1.15±0.24, q=8.227), precancerous group (1.85±0.18, q=12.361) and cancerous group (2.59±0.55, q=18.082). Compared with the control group (0.25±0.11, F=121.103, P<0.001), the degeneration group, the precancerous group and the liver cancer group were up-regulated by 4.6, 7.4 and 10.4-folds, respectively. Immunohistochemistry showed that compared with the control group, the positive rate of Wnt3a in the degeneration group was 66.7% (12/18, χ²=10.701, P=0.001), and both the precancerous and liver cancer groups were positive (9/9, χ²=17.115, P<0.001). Wnt3a expression was gradually increased in liver and blood samples during the process of carcinogenesis, and the difference between two groups was statistically significant (F=176.711, P<0.001). Wnt3a overexpression was secreted into blood stream via cancerous liver tissue, and there was a linear correlation between Wnt3a levels in blood and liver samples (r=0.732, P<0.001). Conclusions: Wnt3a overexpression is closely related with hepatocellular carcinogenesis, and thus may become a new monitoring marker.
Rats ; Animals ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Rats, Sprague-Dawley ; Carcinogenesis/metabolism* ; 2-Acetylaminofluorene ; RNA, Messenger/metabolism* ; Precancerous Conditions