Objective:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

Objective To investigate the prognostic value of serum adenosine deaminase(ADA)and plas-minogen activator inhibitor 1(SERPINE1)levels in patients with type 2 diabetes mellitus(T2DM)complicat-ed with acute cerebral infarction(ACI).Methods A total of 195 patients with T2DM combined with ACI(ACI group)and 174 patients with T2DM alone(control group)admitted to Xi'an Labor Union Hospital from March 2019 to March 2023 were selected.The levels of serum ADA and SERPINE1 were compared be-tween ACI group and control group,and patients with different degrees of neurological defect and prognosis.The influencing factors of poor prognosis in T2DM patients with ACI were analyzed,and the value of each in-dex in predicting poor prognosis was evaluated.Results The levels of ADA and SERPINE1 in ACI group were significantly higher than those in control group(P＜0.05).With the aggravation of neurological deficit in T2DM patients with ACI,serum ADA and SERPINE1 levels increased(P＜0.05).The levels of serum ADA and SERPINE1 in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).Severe neurological deficit and high levels of ADA,SERPINE1 and HbA1c were risk factors for poor prognosis in T2DM patients with ACI(P＜0.05).The area under the curve(AUC)of ADA combined with SERPINE1 for predicting the prognosis of T2DM patients with ACI was 0.896,which was higher than that of Ada and SERPINE1 alone(P＜0.05).Conclusion Elevated serum ADA and SERPINE1 levels are associated with severe neurological deficits and poor prognosis in T2DM patients with ACI.Combined detection of ADA and SERPINE1 can predict poor prognosis in T2DM patients with ACI.

Humans ; Adult ; Invasive Pulmonary Aspergillosis ; Pneumonia, Viral/complications* ; Risk Factors ; Pulmonary Aspergillosis/complications*

Objective:To construct a recombinant herpes simplex virus 2 (HSV-2) expressing enhanced green fluorescent protein (EGFP) using clustered, regularly interspaced, short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology.Methods:Four strategies for inserting exogenous EGFP gene into HSV-2 genome using CRISPR/Cas9 technology were designed: (1) conventional homology-directed repair: circular two homology arm donor-mediated gene knock-in; (2) linearized single homology arm donor-mediated gene knock-in; (3) homology-independent targeted integration; (4) conventional homology-directed repair-mediated by cell lines stably expressing Cas9 and sgRNA.Results:The recombinant virus HSV-2-EGFP was successfully constructed based on the second, the third and the fourth strategies. The second strategy was the most efficient, followed by the third and the fourth strategies. The purified recombinant virus could stably express green fluorescent protein in seven passages and shared similar growth characteristics in Vero cells to the parental virus.Conclusions:Linearized single homology arm donor could increase the efficiency of gene knock-in, and cell lines stably expressing Cas9 and sgRNA could increase the efficiency of gene knock-in mediated by homology-directed repair.

Objective:To investigate the effects of genomic location of a foreign gene in Shanghai-191 strain measles virus (MV) vector on gene expression and virus replication.Methods:The nucleotide sequence encoding S1 protein of SARS-CoV-2 was inserted at different positions in MV antigenome (the upstream of the N gene, between P and M genes, between H and L genes), and co-transfected into 293T cells with helper plasmids coding T7 RNA polymerase and N, P, and L proteins, respectively. The transfected cells were lysed and the supernatants were used to infected Vero cells to harvest recombinant viruses. S1 proteins expressed by the recombinant viruses were identified by RT-PCR, indirect immunofluorescence assay, Western blot and ELISA. Growth kinetics of the recombinant viruses were analyzed.Results:Recombinant viruses were failed to be rescued when the S1 protein-coding sequence was cloned into the upstream of N gene. Two recombinant viruses, MV-M-S1 and MV-L-S1, were successfully rescued when cloning the S1 protein-coding sequence into the intergenic region between P and M genes, or H and L genes, and could express S1 protein. MV-M-S1 expressed more S1 protein than MV-L-S1, but the titer of MV-M-S1 was lower.Conclusions:Inserting a foreign gene at different positions in the MV genome might have different effects on gene expression and virus replication. This study provided reference for the subsequent construction of MV vector.

Objective:To investigate the mechanism of sinomenine (SIN) in inducing the immunosuppressive effects of rat-derived dendritic cells (DCs).Methods:The bone marrow-derived precursor cells from Wistar rats were cultured in vitro. The morphological differences between sinomenine treated DCs (sinomenine modified group, SIN group) and conventional induced DCs (conventional induced group, control group) were observed under microscope. The CD phenotype of DCs was detected by flow cytometry. DCs were induced maturation by lipopolysaccharides (LPS) stimulation. The impact of SIN on the expressions of Toll-like receptor (TLR)2, TLR3 and TLR4 on the DCs surface were detected by flow cytometry. Results:In the conventional induction group, the cells showed clusters or suspension growth, with obvious granular sense on the cell surface; while in the sinomenine induction group, the cells were clustered together, with no significant change in cell volume and morphology. The relative expressions of CD80 and CD86 were 70.7% and 71.3% in the conventional induction group, while 51.7% and 49.4% in the SIN group. The relative expression of TLRs on DCs in SIN + LPS group was TLR2 (51.2±0.34)%, TLR3 (50.3±0.14)%, TLR4 (52.1±0.16)%, which were significantly lower than those in LPS group [(94.35±0.16)%, (97.55±0.16)%, (94.6±0.12)%].Conclusions:SIN may induce immune tolerance by inhibiting the maturation of DCs via inhibiting the TLRs signaling pathways.

Objective:To explore the diagnosis, surgical methods and therapeutic effect of primary duodenal malignant tumor.Methods:The clinical data of 116 patients with primary duodenal malignant tumor from January 2010 to December 2018 were retrospectively analyzed.Results:Among 116 patients, adenocarcinoma was in 74 cases, interstitial tumor was in 25 cases, carcinoid was in 9 cases, the others was in 8 cases. Before operation, duodenoscopy was performed in 107 cases, and CT examination was performed in 76 cases. There were 57 cases of pancreaticoduodenectomy, 15 cases of duodenal segmental resection, 13 cases of subtotal gastrectomy and duodenal bulbar resection, 13 cases of duodenal partial resection, and 18 cases of palliative short circuit operation. The total incidence of postoperative complication was 31.9% (37/116), including pancreatic fistula in 8 cases (grade B 5 cases, grade C 3 cases), biliary fistula in 6 cases, abdominal infection in 5 cases, pulmonary infection in 4 cases, intestinal fistula in 3 cases, delayed gastric emptying in 3 cases, and hemorrhage in 8 cases. Four cases (3.4%) died during the perioperative period. Single factor Cox regression analysis result showed that the postoperative survival time was related to the tumor differentiation degree, operation method, tumor infiltration degree and lymphatic metastasis ( P<0.05 or <0.01); multi-factor Cox regression analysis results showed that the operation method, tumor infiltration degree and lymphatic metastasis were the independent risk factors for the postoperative survival time of patients with primary duodenal malignant tumor ( P<0.05). The patients were followed up until June 2021, and 9 cases were lost to follow-up. Kaplan-Meier survival curve analysis result showed that the postoperative overall 1-,3- and 5-year survival rates were 82.11%, 57.56% and 33.11%, respectively. Conclusions:Adenocarcinoma is the main primary malignant tumor of duodenum. Duodenoscopy and CT are the main examination methods. Radical resection is the most effective treatment for primary duodenal malignant tumor, and pancreaticoduodenectomy is the first choice. Surgical method, tumor infiltration degree and lymphatic metastasis are the independent risk factors affecting the prognosis of patients.

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

Objective To compare the influences of microsurgical clipping and intravascular interventional embolization on the nerve function recovery in patients with posterior communicating aneurysm combined with oculomotor paralyses.Methods Eighty-six patients with posterior communicating artery aneurysm accompanied by oculomotor nerve palsy admitted to Qianjiang Central Hospital of Chongqing from May 2015 to May 2017 were randomly divided into observation group (n =43) and control group (n =43) by random number table method.The control group was treated with microsurgical clipping,while the observation group was treated with intravascular interventional embolization.The therapeutic effect,neurological function recovery,postoperative complications and prognosis of the two groups were compared.Results The operation time,intraoperative blood loss,postoperative respiratory recovery time and postoperative extubation time of the observation group were significantly less than those of the control group (P ＜ 0.05);the complete recovery of the observation group was significantly higher than that of the control group,and no recovery was significantly lower than that of the control group (P ＜ 0.05);the incidence of complications in the observation group was significantly lower than that in the control group (P ＜ 0.05);the proportion of 5 points in the observation group was significantly higher than that in the control group (P ＜ 0.05).Conclusions Intravascular interventional embolization in the treatment of posterior communicating aneurysm combined with oculomotor paralyses can promote the recovery of nerve function,reduce the incidence of postoperative complications,have a good prognosis and a definite effect,which can be used as the first choice of treatment.

Objective:To investigate the prognostic significance of preoperative neutrophil-lymphocyte ratio(NLR)combined with tu-mor-associated neutrophils(TANs)in the stroma of gastric cancer tissues of patients.Methods:One hundred and twenty-six gastric cancer tissue samples from patients enrolled in Changhai hospital from June 2006 to May 2011 were divided into four groups accord-ing to NLRs in preoperative peripheral blood combined with high or low infiltration of neutrophils in gastric cancer tissues.The 5-year survival of the four groups was then compared,and their correlations with clinicopathologic features and prognosis were analyzed.Re-sults:High NLRs in peripheral blood combined with low infiltrating TANs in gastric tissues was associated with lower differential grade (P<0.001)and larger tumor size(P=0.026).Of the four groups,patients with high NLR in peripheral blood combined with low infiltrat-ing TANs in gastric cancer tissues demonstrated the lowest survival rates,whereas those with low NLR and high infiltrating TANs had highest survival rates, and this difference was statistically significant (P<0.05). Univariate and multivariate Cox regression analyses showed that high NLR in peripheral blood combined with low infiltrating TANs in gastric cancer tissues(P<0.05)was an independent factor indicating poor prognosis.Conclusions:NLR in preoperative peripheral blood combined with infiltrating TANs in gastric cancer tissues can be used as a prognostic indicator for patients with gastric cancer,especially high NLR in preoperative peripheral blood com-bined with low infiltrating TANs in gastric cancer tissue indicates poor prognosis.