OBJECTIVE: Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome). METHODS: We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period. RESULTS: Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated. CONCLUSION Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
Rats ; Animals ; Arsenic/toxicity* ; Fluorides ; RNA, Ribosomal, 16S/genetics* ; Rats, Sprague-Dawley ; Metabolome ; Microbiota

Aim To study the therapeutic effect of helicid on osteoarthritis (OA) of joint instability model, and explore the mechanism of helicid in the treatment of OA. Methods A rat knee model of OA was established by the medial meniscectomy (MMx) method. After treatment with helicid, HE and safranin O/fast green staining methods were used to observe the his-topathological changes of rat knee articular cartilage; Western blot was used to detect the protein expression level of Trpvl in rat synovial tissue. Immunohistochemical staining was used to examine the expression of Trpvl in rat knee articular cartilage and synovial tissues. Results Helicid significantly slowed down the degeneration of rat knee articular cartilage as shown by HE and safranin O/fast green staining. Western blot results showed that helicid down-regulated the expression of Trpvl in rat synovial tissue examined. Immunohistochemical results showed that helicid significantly reduced the expression of Trpvl in both of knee articular cartilage and synovial tissues. Conclusions Helicid prominently decreases MMx-induced articular cartilage damage and cartilage matrix loss, thereby exerting a therapeutic effect on OA.

Objective:To analyze the effects of microvascular invasion (MVI) and anatomical hepatectomy on early recurrence and survival of patients with hepatocellular carcinoma (HCC).Methods:The data of 246 patients with HCC admitted to 215 Hospital of Shaanxi Nuclear Industry, Chinese PLA General Hospital and Beijing Tsinghua Chang Gung Hospital from July 2008 to June 2019 were retrospectively analyzed, including 208 males and 38 females, aged (53.8±9.6) years. According to the occurrence of MVI, 246 patients were divided into the MVI group ( n=83) and control group ( n=163, without MVI). Hepatitis B virus (HBV) infection, preoperative alpha-fetoprotein (AFP), maximum tumor diameter, intraoperative blood loss were compared between the two groups. The recurrence-free survival and cumulative survival were compared between the two groups before and after the inverse probability weighted correction for propensity score. Results:The propensity score was calculated by logistic regression model. After inverse probability weighted correction, the virtual sample size was 247 cases (82 cases in MVI group and 165 cases in control group). The proportion of HBV infection, with a serum level of AFP > 200 μg/L, the maximum diameter of tumor and the intraoperative blood loss were higher in MVI group (all P<0.05). The risk of early recurrence in patients undergoing anatomical hepatectomy ( n=107) was lower than that in patients undergoing non-anatomical hepatectomy ( n=139) (univariate Cox regression analysis of HR=1.60, 95% CI: 1.06 to 2.42, P=0.020), but the overall survival was comparable (univariate Cox regression analysis of HR=1.66, 95% CI: 0.80 to 3.42, P=0.200). The recurrence-free survival (RFS) of MVI group was lower than that of the control group, and the postoperative cumulative survival rate was also lower before the inverse probability weighted correction of the tendency score. The RFS in MVI group was lower than that in control group after the tendency score was adjusted by inverse probability weighting ( HR=2.62, 95% CI: 1.61 to 4.27, P<0.001). There was no significant difference in the cumulative survival between the MVI and control group ( HR=2.09, 95% CI: 0.89 to 4.93, P=0.050). Conclusion:MVI is associated with early postoperative recurrence in patients with HCC, and the early recurrence rate after anatomical hepatectomy is lower than that after non-anatomical hepatectomy.

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

Objective:To observe the effect of noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen therapy (HFNC) on the prognosis of patients with coronavirus disease 2019 (COVID-19) accompanied with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology when authors worked as medical team members for treating COVID-19. COVID-19 patients with pulse oxygen saturation/fraction of inspiration oxygen (SpO 2/FiO 2, S/F) ratio < 235, managed by medical teams [using S/F ratio instead of oxygenation index (PaO 2/FiO 2) to diagnose ARDS] from February to April 2020 were included. The patients were divided into NIPPV group and HFNC group according to their oxygen therapy modes. Clinical data of patients were collected, including general characteristics, respiratory rate (RR), fraction of FiO 2, SpO 2, heart rate (HR), mean arterial pressure (MAP), S/F ratio in the first 72 hours, lymphocyte count (LYM), percentage of lymphocyte (LYM%) and white blood cell count (WBC) at admission and discharge or death, the duration of dyspnea before NIPPV and HFNC, and the length from onset to admission. The differences of intubation rate, all-cause mortality, S/F ratio and RR were analyzed, and single factor analysis and generalized estimation equation (GEE) were used to analyze the risk factors affecting S/F ratio. Results:Among the 41 patients, the proportion of males was high (68.3%, 28 cases), the median age was 68 (58-74) years old, 28 cases had complications (68.3%), and 34 cases had multiple organ dysfunction syndrome (MODS, 82.9%). Compared with HFNC group, the proportion of complications in NIPPV group was higher [87.5% (21/24) vs. 41.2% (7/17), P < 0.05], and the value of LYM% was lower [5.3% (3.4%-7.8%) vs. 10.0% (3.9%-19.7%), P < 0.05], the need of blood purification was also significantly lower [0% (0/24) vs. 29.4% (5/17), P < 0.05]. The S/F ratio of NIPPV group gradually increased after 2 hours treatment and RR gradually decreased with over time, S/F ratio decreased and RR increased in HFNC group compared with baseline, but there was no significant difference in S/F ratio between the two groups at each time point. RR in NIPPV group was significantly higher than that in HFNC group after 2 hours treatment [time/min: 30 (27-33) vs. 24 (21-27), P < 0.05]. There was no significant difference in rate need intubation and hospital mortality between NIPPV group and HFNC group [66.7% (16/24) vs. 70.6% (12/17), 58.3% (14/24) vs. 52.9% (9/17), both P > 0.05]. Analysis of the factors affecting the S/Fratio in the course of oxygen therapy showed that the oxygen therapy mode and the course of illness at admission were the factors affecting the S/F ratio of patients [ β values were -15.827, 1.202, 95% confidence interval (95% CI) were -29.102 to -2.552 and 0.247-2.156, P values were 0.019 and 0.014, respectively]. Conclusion:Compared with HFNC, NIPPV doesn't significantly reduce the intubation rate and mortality of patients with COVID-19 accompanied with ARDS, but it significantly increases the S/F ratio of those patients.

Objective:To investigate the related factors of vertebral body height reloss after pedicle screw fixation of thoracolumbar fracture and to determe the optimum prediction point.Methods:A retrospective case control study was made on 215 patients with thoracolumbar fracture admitted to Second Affiliated Hospital of Soochow University from January 2010 to December 2017. There were 155 males and 60 females，aged 21-80 years［（48.6±10.4）years］. According to Denis fracture classification，there were 73 patients with compression fractures（type A in 15 patients，type B in 51，type C in 7），135 burst fractures（type A in 28 patients，type B in 87，type C in 20）and flexion distraction fractures（type A in 4，type B in 2，type C in 1）. All patients were treated by pedicle screw fixation. Follow-up lasted for 12- 48 months［（23.8±8.2）months］. Vertebral body height loss occurred in 86 patients（loss group），but did not in 129 patients（non-loss group）. The two groups were compared concerning sex，age，osteoporosis self-assessment tool for Asians（OSTA），body mass index（BMI），fracture types，number of fractured vertebrae，preoperative sagittal Cobb angle，preoperative degree of vertebral compression，number of screws placed in injured vertebrae，extent of vertebral reset and other related factors. Univariate analysis was used to identify the correlation of those factors with vertebral body height reloss. Multivariate Logistic regression analysis was performed to identify the independent factors for the height reloss with the receiver operating characteristic curve（ROC）and area under the curve（AUC）calculated to evaluate the optimum point in prediction of vertebral height reloss.Results:The two groups showed no significant differences in sex，age，BMI，fracture types，number of injured vertebrae，preoperative sagittal Cobb angle and number of screws placed in injured vertebrae（ P>0.05），but the differences were statistically significant in OSTA，preoperative degree of vertebral compression and extent of vertebral reset（ P<0.05）. According to the univariate analysis，OSTA，preoperative degree of vertebral compression and extent of vertebral reset were significantly correlated with the occurrence of vertebral body height reloss（ P<0.05）. According to the multivariate Logistic regression，OSTA（ OR=1.109，95% CI 0.527-0.685， P<0.05）and preoperative degree of vertebral compression（ OR =0.038，95% CI 0.539-0.689， P<0.05）were significantly related to vertebral body height reloss. The AUC relating OSTA and preoperative degree of vertebral compression to vertebral body height reloss was 0.604 and 0.614，respectively. The optimum prediction point of OSTA and preoperative degree of vertebral compression for vertebral body height reloss was 1.9 and 31.3%，respectively. Conclusions:OSTA and the preoperative degree of vertebral compression are independent risk factors for vertebral body height reloss. OSTA≤1.9 or preoperative degree of vertebral compression ≥31.3% indicates a significantly higher risk of postoperative vertebral body height reloss.

Objective::To investigate the role and mechanism of Testudinis Carapax et Plastrum aqueous extract in promoting osteogenic differentiation of mouse preosteoblast cell line(MC3T3-E1) by regulating nuclear transcription factor-κB(NF-κB) inflammation microenvironment. Method::MC3T3-E1 cells were cultured in vitro, and osteogenic induction (OI) was performed. Testudinis Carapax et Plastrum was prepared and treated the cells. Cells were devided into control group, osteogenic induction group and Testudinis Carapax et Plastrum (20 mg·L^-1)with osteogenic induction group. The proliferation of MC3T3-E1 was detected by cell counting kit-8 (CCK-8), and the optimum concentration of intervention was determined. MC3T3-E1 differentiation and osteogenic mineralization were assayed using alkaline phosphatase (ALP) and Alizarin red staining (ARS), respectively. The expressions of NF-κB p65, NF-κB p105, interleukin-6(IL-6), ALP and Collagen-Ⅰ(COL-Ⅰ) mRNA were detected by Real-time PCR. Result::The results of CCK-8 showed that the proliferation of MC3T3-E1 did not change statistically with time, but it showed an upward trend, while the proliferation at 20 mg·L^-1 was more obvious than other groups. The ALP and ARS showed that the positive staining rate of osteogenic induction group and Testudinis Carapax et Plastrum with osteogenic induction group were higher than control group.Real-time PCR results showed that on the 7^th day in culture, the expression of NF-κB p105 and IL-6 mRNA in Testudinis Carapax et Plastrum with osteogenic induction group was significantly lower than that in control group (P<0.01), and the expression of ALP and COL-Ⅰ mRNA was significantly upregulated(P<0.05), on the 14^th day, the expression of NF-κB p65, NF-κB p105 and IL-6 mRNA in Testudinis Carapax et Plastrum with osteogenic induction group was significantly lower than that in control group (P<0.01). The expression of ALP and COL-Ⅰ mRNA was significantly increased (P<0.05, P<0.01). Conclusion::Testudinis Carapax et Plastrum aqueous extract can promote osteogenic differentiation of MC3T3-E1 via a mechanism associated with the regulation of inhibition of NF-κB inflammatory microenvironment.