Salvianolic acid B exerts its anti-tumor immunity by targeting USP2 and reducing the PD-L1 level / 药学学报

With the development of small-molecule immunotherapy drugs, its combination with the programmed cell death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibodies would provide a new opportunity for cancer treatment. Therefore, targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity and considered as the next generation of tumor immunotherapy. In the present study, we investigated the anti-tumor role of salvianolic acid B (SAB) by regulating the PD-L1 level in tumors. Changes of total PD-L1 and membrane PD-L1 levels were determined by Western blot, flow cytometry and PD-1/PD-L1 interaction assays. The expression of mRNA level of PD-L1 was detected by real-time PCR. The cytotoxicity of activated peripheral blood mononuclear cell (PBMC) cells toward co-cultured tumor cells was measured by cell impedance assay and crystal violet experiment. Surface plasma resonance technique was used to analyze the direct interaction between SAB and ubiquitin carboxyl-terminal hydrolase 2 (USP2). The antitumor effect of SAB in vivo was examined by C57BL/6 mice bearing MC38 xenograft tumor (all animal experiments were conducted in accordance with the Animal Ethics Committee of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences). Western blot and flow cytometry assay showed that SAB can significantly downregulate the abundance of PD-L1 in RKO and PC3 cells in dose- and time-dependent manner. PD-1/PD-L1 binding assay revealed that SAB reduces the binding of tumor cells to recombinant PD-1 protein. Mechanism studies revealed that SAB can bind directly to USP2 protein and inhibit its activity, thus promote the ubiquitin-proteasome pathway degradation of PD-L1 proteins. In addition, Cell impedance and crystal violet staining indicated that SAB enhances the killing activity of co-cultured PBMC cells toward tumor cells. MC38 tumor transplanted mouse experiments revealed that SAB treatment displayed significant suppression in the growth of MC38 tumor xenografts in C57BL/6 mice with an inhibition rate of 63.2% at 20 mg·kg-1. Our results demonstrate that SAB exerts its anti-tumor activity by direct binding and inhibiting the activity of USP2 and reducing the PD-L1 level. Our study provides an important material basis and scientific basis for the potential application of SAB in tumor immunotherapy drug targeting USP2-PD-L1 axis.

A case of poisoning by oral lime sulfur / 中华劳动卫生职业病杂志

Lime sulfur is a common bactericide with strong alkalinity, and is highly corrosive to humans and animals. It is rare for lime sulfur poisoning clinically. This article discusses the clinical manifestations of a patient who was poisoned by oral lime sulfur. After the poisoning, the mucosa of the lips and pharynx broke, fever, and pulmonary inflammation quickly appeared. The pulmonary CT showed slight interstitial changes in both lungs. Through high flow oxygen inhalation, fluid infusion, drainage, maintenance of water and electrolyte balance, protection of important organ functions, and other symptomatic support and treatment, as well as control of blood pressure, blood sugar, maintenance of circulatory function and other targeted measures, the patient's condition gradually improved.

A pre-conception cohort study of fertility and its related factors among couples with the intention of conception / 中华预防医学杂志

Objective: To describe fertility and explore factors associated with it among pre-conception couples of childbearing age. Methods: Based on the pre-conceptional offspring trajectory study of the School of Public Health of Fudan University, couples of childbearing age who participated in the pre-conception physical examination in Shanghai Jiading District from 2016 to 2021 were recruited and followed up. Couples' time to pregnancy (TTP) was analyzed and Cox proportional hazards regression model was used to explore the factors associated with TTP. Kaplan-Meier was used to calculate each menstrual cycle's cumulative pregnancy rate. Results: A total of 1 095 preconception couples were included in the analysis, the M(Q1,Q3)of TTP was 4.33 (2.41, 9.78) menstrual cycles. Age of women (FR=0.90, 95%CI: 0.85-0.95, P<0.001), women who were overweight or obese before pregnancy (FR=0.36, 95%CI: 0.24-0.55, P<0.001), women who were exposed to second-hand smoking (FR=0.63, 95%CI: 0.44-0.92, P=0.016), women whose home or office had been renovated in the past 2 years and had a particular smell (FR=0.46, 95%CI: 0.26-0.81, P=0.008) were risk factors for impaired fertility. Regular menstrual cycles (FR=1.64, 95%CI: 1.16-2.31, P=0.005), females who often drank tea/coffee (FR=1.55, 95%CI: 1.11-2.17, P=0.011) and males who took folic acid before conception (FR=2.35, 95%CI: 1.38-4.23, P=0.002) were associated with better fertility. The cumulative pregnancy rate of 3, 6, and 12 menstrual cycles was 37.6%, 64.4%, and 78.4%, respectively. Conclusion: Older couples, overweight or obesity before pregnancy, irregular menstruation, exposure to secondhand smoke and decoration pollutants in females are associated with impaired fertility. Frequent tea/coffee drinking before pregnancy in females and taking folic acid before pregnancy in males are associated with shortened conception time.

Clinical characteristics of plastic bronchitis and risk factors for recurrence in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB.@*METHODS@#This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed.@*RESULTS@#A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05).@*CONCLUSIONS@#Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

Clinical features of children with febrile seizures caused by Omicron variant infection / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with febrile seizures after Omicron variant infection.@*METHODS@#A retrospective analysis was performed on the clinical data of children with febrile seizures after Omicron variant infection who were admitted to the Department of Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, from December 1 to 31, 2022 (during the epidemic of Omicron variant; Omicron group), and the children with febrile seizures (without Omicron variant infection) who were admitted from December 1 to 31, in 2021 were included as the non-Omicron group. Clinical features were compared between the two groups.@*RESULTS@#There were 381 children in the Omicron group (250 boys and 131 girls), with a mean age of (3.2±2.4) years. There were 112 children in the non-Omicron group (72 boys and 40 girls), with a mean age of (3.5±1.8) years. The number of children in the Omicron group was 3.4 times that in the non-Omicron group. The proportion of children in two age groups, aged 1 to <2 years and 6-10.83 years, in the Omicron group was higher than that in the non-Omicron group, while the proportion of children in two age groups, aged 4 to <5 years and 5 to <6 years, was lower in the Omicron group than that in the non-Omicron group (P<0.05).The Omicron group had a significantly higher proportion of children with cluster seizures and status convulsion than the non-Omicron group (P<0.05). Among the children with recurrence of febrile seizures, the proportion of children aged 6-10.83 years in the Omicron group was higher than that in the non-Omicron group, while the proportion of children aged 3 years, 4 years, and 5 years in the Omicron group was lower than that in the non-Omicron group (P<0.05).@*CONCLUSIONS@#Children with febrile seizures after Omicron variant infection tend to have a wider age range, with an increase in the proportion of children with cluster seizures and status convulsion during the course of fever.

The inhibitory effect of ozanimod on the growth and biofilm formation of Staphylococcus aureus / 中国热带医学

@#Abstract: Objective　To screening new compounds that can inhibit the growth and biofilm formation of Staphylococcus aureus. Methods　Compounds that can inhibit the growth of Staphylococcus aureus were screened from the FDA approved drug library by 96 well plates. The absorbance value of 600 nm wavelength (OD600) was measured by Microplate Reader to detect the growth of Staphylococcus aureus planktonic cells in the culture supernatant. The minimum inhibitory concentration (MIC) of ozanimod against Staphylococcus aureus clinical isolates were detected by micro broth dilution method. The inhibitory effect of sub-inhibitory concentrations of ozanimod on the biofilm formation of Staphylococcus aureus was detected by crystal violet staining. Results　This study found that ozanimod could significantly inhibit the growth of Staphylococcus aureus SA113 (screening reference strain), and the MIC was 25.00 μmol/L. The MIC of ozanimod against 119 clinical isolates of Staphylococcus aureus [65 isolates of methicillin sensitive (MSSA) and 54 isolates of methicillin resistant (MRSA)] was 12.50 or 25.00 μmol/L. The MIC50 and MIC90 of ozanimod against the 119 Staphylococcus aureus isolates all were 25.00 μmol/L. This study found that 6.25, 12.50, 25.00 μmol/L of ozanimod could significantly inhibit the biofilm formation of 2 MSSA and 2 MRSA. The sub-MIC concentration of ozanimod (12.50 μmol/L) could significantly inhibit the biofilm formation of 14 MSSA and 11 MRSA, but had no inhibitory effect on the growth of planktonic cells of these Staphylococcus aureus isolates. Conclusion　Ozanimod can inhibit the growth of Staphylococcus aureus, including MRSA, and has good antibacterial activity. The sub-MIC concentration of ozanimod could significantly inhibit the biofilm formation of Staphylococcus aureus.

Research progresses on NLRP3 inflammasomes-induced anti-tumor immunity / 药学学报

More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8+ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.

Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells

SUMMARY OBJECTIVE: This study aimed to assess the effect of the collagen/silk fibroin scaffolds seeded with human umbilical cord-mesenchymal stem cells on functional recovery after acute complete spinal cord injury. METHODS: The fibroin and collagen were mixed (mass ratio, 3:7), and the composite scaffolds were produced. Forty rats were randomly divided into the Sham group (without spinal cord injury), spinal cord injury group (spinal cord transection without any implantation), collagen/silk fibroin scaffolds group (spinal cord transection with implantation of the collagen/silk fibroin scaffolds), and collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (spinal cord transection with the implantation of the collagen/silk fibroin scaffolds co-cultured with human umbilical cord-mesenchymal stem cells). Motor evoked potential, Basso-Beattie-Bresnahan scale, modified Bielschowsky's silver staining, and immunofluorescence staining were performed. RESULTS: The BBB scores in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group were significantly higher than those in the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). The amplitude and latency were markedly improved in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). Meanwhile, compared to the spinal cord injury and collagen/silk fibroin scaffolds groups, more neurofilament positive nerve fiber ensheathed by myelin basic protein positive structure at the injury site were observed in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (p<0.01, p<0.05). The results of Bielschowsky's silver staining indicated more nerve fibers was observed at the lesion site in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.01, p< 0.05). CONCLUSION: The results demonstrated that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen/silk fibroin scaffolds could promote nerve regeneration, and recovery of neurological function after acute spinal cord injury.

Shenling Baizhu Powder () Ameliorates Pi (Spleen)-Deficiency-Induced Functional Diarrhea in Rats / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of Pi (Spleen)-deficiency-induced functional diarrhea (FD) model rats treated by Shenling Baizhu Powder (, SBP).@*METHODS@#Thirty male Sprague-Dawley rats were randomly divided into 5 groups including control, model, low-, medium-, and high-dose SBP groups (SBPLDG, SBPMDG, SBPHDG), 6 rats in each group, respectively. Pi-deficiency-induced FD rats model was developed through Radix et Rhizoma Rhei gavage for 7 days. After modeling, the rats were treated with 3 doses of SBP [0.93, 1.86, and 3.72 g/(kg·d)], and the rats in the control and model groups were given pure water for 7 days. The diarrhea index was calculated. On the 7th and 14th days, the traveled distance of rat was measured by the open field test. Serum D-xylose content was determined by the phloroglucinol method and interleukin (IL)-10 and IL-17 levels were measured using an enzyme-linked immunosorbent assay kit. The content of Treg cells was determined by flow cytometry.@*RESULTS@#Compared with the control group, the diarrhea index and IL-17 level in the model group were significantly higher and the total exercise distance and D-xylose content significantly decreased (P>0.05). The expression of IL-10 in the SBPHDG group was significantly up-regulated, and serum D-xylose level and Treg cells increased significantly compared with the model group (P>0.05).@*CONCLUSION@#High-dose SBP exhibited ameliorating effects against Pi-deficiency induced FD, which might be attributed to its modulations on intestinal absorption function as well as adaptive immunity in mesenteric lymph nodes of rat.

PD-1/PD-L1 expression and its interaction with interferon-γ in Toxoplasma gondii-infected mice at middle and late pregnancy / 中国血吸虫病防治杂志

Objective To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). Methods A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. Results Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (rs = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (rs = 0.97, P < 0.01) and in placental (rs = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (rs = 0.81, P < 0.01). Conclusions Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.

Research Progress on Chemical Constituents and Pharmacological Effects of Asari Radix et Rhizoma / 中国实验方剂学杂志

Asari Radix et Rhizoma （ARR） is a traditional Chinese medicine for relieving exterior syndrome， and its roots and stems contain rich chemical components， including volatile oils （terpenoids， aromatics and aliphatics）， lignans， flavonoids， etc. Clinically， it has been traditionally used for the treatment of diseases such as phlegm and cough， anemofrigid cold， rheumatic arthralgia due to its ability to spread cold. Modern pharmacological studies have shown that ARR played beneficial roles in analgesic， anti-inflammatory， antitussive， antiasthmatic， antiviral， antibacterial， sedative， antioxidative， and antidepressant responses， antihypertension， as well as tumor suppression. The current studies on the chemical composition of ARR mainly focused on volatile components， and little information is available for the occurrence and pharmacological effects of non-volatile components. In addition， there is a lack of clear classification of chemical components and the distribution of chemical components in medicinal parts and the origin of species. Therefore， in this study， the authors reviewed a large number of literature on the chemical compositions and pharmacological effects of ARR， and hoping to provide a reference for further pharmacological research and the new drug development of ARR.

Study on the mechanisms of the intestinal tight-junction destruction caused by Blastocystis hominis infection in rats / 中国血吸虫病防治杂志

Objective To explore the mechanism of the intestinal barrier damage caused by Blastocystis hominis infections in rats. Methods Thirty SD rats were randomly divided into the control group, and the 1-, 3-, 6- and 9-week-infection groups, of 6 rats in each group. Rats in each infection group were orally infected with B. hominis trophozoites at a density of 2 × 108 parasites per rat, and the control group was given an equal volume of phosphate buffered saline solution. The 7-hour urine samples were collected 1, 3, 6 and 9 weeks post-infection for the measurement of the intestinal permeability. Then, rats were sacrificed using the cervical dislocation method, and the cecum specimens were collected for the detection of the intestinal epithelial cell permeability. The expression of tight junction-related Occludin and Claudin - 1 genes and apoptosis-related Bcl - 2 and Bax genes was quantified in cecum epithelial cells using the real-time fluorescent quantitative PCR (qPCR) assay, and cell apoptosis was detected in the rat cecum using the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Results The median urinary lactolose to mannitol ratios were 0.29, 0.72, 0.44, 0.46 and 0.38 in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 12.09, P < 0.05). B. hominis invasion and epithelial injury were observed in intestinal epithelial cells of rats infected with B. hominis, and transmission electron microscopy displayed the destruction of tight junctions between intestinal epithelial cells. The relative expression of Occludin, Claudin-1, Bcl-2 and Bax genes was 1.04, 0.62, 0.71, 0.68 and 0.96; 1.03, 0.61, 0.63, 0.76 and 0.86; 1.08, 0.70, 0.75, 0.74 and 1.03; and 1.00, 1.57, 1.33, 1.35 and 1.10 in the control group and the 1-, 3-, 6- and 9-week-infection groups, respectively, and all differences were statistically significant (F = 2.86, 2.85, 3.37 and 4.45, all P values < 0.05). The median number of positive staining cells were 1.00, 13.00, 9.00, 3.50 and 1.00 in rat cecum specimens in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 22.95, P < 0.01). Conclusion B. hominis infection may cause an increase in the rat intestinal permeability through triggering the apoptosis of intestinal epithelial cells to destroy the tight junction between intestinal epithelial cells, thereby destroying the intestinal barrier function.

Expression of hypoxia-inducible factor-1 in mice infected with Toxoplasma gondii during pregnancy / 中国血吸虫病防治杂志

Objective To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. Methods Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1α, HIF-1β and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1α and VEGF mRNA expression was examined. In addition, and the HIF-1α expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. Results Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1α (F = 132.6, P < 0.05) and HIF-1β mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1α (F = 111.5, P < 0.05) and HIF-1β mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1α and HIF-1β mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1α expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1α expression was detected in mouse uterine specimens. Conclusions HIF-1α expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1α inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes.

Differential proteomic analysis of children infected with respiratory syncytial virus

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.

Two-generation reproductive toxicity of lufenuron in SD rats / 中国职业医学

OBJECTIVE: To obtain information on the toxicity of lufenuron on the reproduction ability and the growth and development of offspring in female and male rats through two-generation reproduction toxicity study. METHODS: The specific pathogen free healthy SD rats were randomly divided into control group and low-, medium-and high-dose lufenuron groups, with 60 rats in each group, half females and half males. Rats in the low-, medium-and high-dose lufenuron groups were respectively fed with lufenuron at the dose of 5.0, 20.0 and 80.0 mg/(kg body weight·day) for 8 weeks before mating. The control group was fed with standard foot. The reproductive index, brain and reproductive organ coefficients and pathological changes were observed in P and F1 parents. The birth and growth indexes of the offspring were measured. RESULTS: i) P generation: from the 14 th day, the female rats in the medium-dose group had lower body weight than that of the female control group(P<0.05); from the 35 th day, the body weight was lower than that of the female low-dose group(P<0.05). From the 14 th day, the female rats in the high-dose group had lower body weight than that of the other three female groups(P<0.05). From the 14 th day, the male rats in the medium-and high-dose groups had lower body weight than that of the male control group and low-dose group(P<0.05). The body weight of pregnant rats in the parental high-dose group was lower than that of the control group, low-dose group, and medium-dose group at day 0, 7, 14, 19 of the pregnancy duration(P<0.05). The body weight of pregnant rats in the parental medium-dose group was lower than that of the low-dose group on day 0 of the pregnancy duration, and lower than that of the control and low-dose groups on day 7 and 14(P<0.05). The conception rate, the new-borne survival rates and the feeding survival rate of female rats in the high-dose group was lower than that of the other three female groups(P<0.008). The new-borne feeding survival rate of female rats in the medium-dose group was lower than that of the control group and low-dose group(P<0.008). The organ coefficients of brain in female rats in the medium-and high-dose groups were higher than that of the female control group and low-dose group(P<0.05). The organ coefficients of brain and testis in male rats in the medium-and high-dose groups were higher than that of the control group and low-dose group(P<0.05). The organ coefficient of epididymis in male rats in the high dose group was lower than that of the other three male groups(P<0.05). ii) F1 generation: the body weight of female rats in the low-and medium-dose group was higher than that of the female control group on the 42 th day(P<0.05). The body weight of male rats in the low-dose group was higher than that of the male control group on the 42 th, 49 th, and 56 th days(P<0.05). The body weight of male rats in the medium-dose group was higher than that of the male control group on the 14 th, 21 th, 42 th, 49 th, and 56 th days(P<0.05). The new-borne survival rate in the low-dose group was lower than that of the control group(P<0.017). The body weight of new-borne rats in the high-dose group on day 4 of birth was lower than that in the other three female groups(P<0.05). iii) F2 generation: the body weight of male rats in the male medium-dose group was lower than that in the control group on day 21 of birth(P<0.05). CONCLUSION: The reproductive and developmental toxicity of lufenuron is found in rats in the medium-and high-dose groups. Toxicities including low body weight, conception rate, new-borne survival rate and feeding survival rate are found in P generation; low body weight and feeding survival rate are found in F1 generation; low body weight is found in male F2 generation. The no-observed-adverse-effects levels of lufenuron in two-generation reproductive study are 5.87 mg/(kg·d) for females and 5.09 mg/(kg·d) for males in SD rats.

Study on the levels and risk factors of Vitamin D from preconception to pregnancy / 中华疾病控制杂志

Objective To investigate the levels of serum Vitamin D(VD) from preconception to pregnancy in Jiading district of Shanghai, and explore the risk factors of VD concentration deficiency in the second and third trimester of pregnancy. Methods A total of 94 women who planned to have antenatal care and delivery in Maternal and Child Health Hospital of Jiading district of Shanghai from September 2016 to December 2018 were recruited as the study participants. Chemiluminescent immunoassay (CLIA) was used to examine the concentration of women’s serum VD from preconception to pregnancy. A total of 282 serum samples were detected. Results The prevalence of VD deficiency among 94 women from preconception to pregnancy were 40.4%,57.4% and 48.9% respectively. Results of the mixed linear model showed that women who had dyed or permed hair within the past 1 year had significantly lower serum VD levels during pregnancy (P<0.05), and women who often drank milk and ate deep-sea fish during pregnancy had higher VD levels during pregnancy (P<0.05). Conclusions VD deficiency was common among women in Jiading district of Shanghai, and it should be emphasized to supplement VD before and during pregnancy.

Evaluation and Early Diagnosis of Gastrointestinal Failure in Acute Pancreatitis / 中国医学科学院学报

To investigate the application of Acute Gastrointestinal Injury(AGI) grading in evaluating gastrointestinal failure in patients with acute pancreatitis(AP). In this retrospective observational study,patients presented with moderate severe AP and severe AP in our hospital from October 2013 to October 2016 were consecutively enrolled.Logistic regression analysis and receiver operating characteristic curve were used to explore and evaluate potential predictors of gastrointestinal failure. A total of 202 patients were included in this study,with 90 cases(44.6%) identified as gastrointestinal failure.Survival curve showed significantly increased risk of death in patients with gastrointestinal failure( < 0.05).Logistic regression analysis showed age(=1.06,95%:1.03-1.09,<0.001),complaint of stopping flatus and defecation(=7.02,95%:2.08-23.66,=0.002),increased counts of white blood cells in peripheral blood(=1.09,95%:1.02-1.17,=0.015),decreased level of serum albumin(=0.93,95%:0.86-1.00,=0.048),and increased level of serum creatinine at admission(=1.02,95%:1.01-1.04,=0.001) were the independent risk factors of gastrointestinal failure.The area under curves of Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and Beside Index for Severity in Acute Pancreatitis (BISAP) scores in diagnosing gastrointestinal failure were 0.999 and 0.782,respectively. Gastrointestinal failure can remarkably increase the risk of death in patients with AP.Both APACHE Ⅱ and BISAP scores at admission are useful in diagnosing gastrointestinal failure in patients with AP.

Acute 1,2-dichloroethane exposure induced differential gene expression of liver phaseⅠmetabolic enzymes in SD rats / 中国职业医学

OBJECTIVE: To investigate the effect of 1,2-dichloroethane(1,2-DCE) acute inhalation exposure on the differential gene expression of phase Ⅰ metabolic enzymes. METHODS: The specific pathogen free SD rats were randomly divided into control group(16 rats), low-and high-dose groups(24 rats in each group, half males and half females). Low-and high-dose group were given daily 600, 1 800 mg/m~(3 ) of 1,2-DCE, and the control group given the fresh air by dynamic inhalation for 8 hours per day for consecutive 7 days. After the end of exposure, the relative mRNA expression of cytochrome P450 2 E1(CYP2 E1), alcohol dehydrogenase(ADH1) and acetaldehyde dehydrogenase 3 alpha 1(ALDH3α1) in the liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS: The relative expression of CYP2 E1 in male high-dose group was higher than that in male low-dose group and female high-dose group(P<0.05). The relative expression of ADH1 in male low-and high-dose groups was higher than that in male control group(P<0.05). The relative expression of ADH1 in male high-dose group was higher than that in male low-dose group and female high-dose group(P<0.05). The relative expression of ALDH3α1 in high-dose group was higher than that in control group and low-dose group(P<0.05). CONCLUSION: High dose 1,2-DCE could increase the gene expression of phase Ⅰ metabolic enzymes in rat liver. The 1,2-DCE has more obvious effect in male rats than in female rats.

Effects of 1,2-dichloroethane subacute exposure on depressive behavior and monoamine neurotransmitter level in rats / 中国职业医学

OBJECTIVE: To investigate the effects of 1,2-dichloroethane(1,2-DCE) subacute exposure on depression in rats as well as the relevant mechanism of monoamine neurotransmitters. METHODS: The specific pathogen free male SD rats were randomly divided into control group, low-, medium-, and high-dose groups, with 10 rats in each group. The rats in these 4 groups were intra-gastrically administered with 1,2-DCE(diluted in corn oil) at the dose of 0, 20, 40, 80 mg/kg body weight, every other day for 14 times. After exposure, the behavior change of rats was observed by open-field test, sucrose preference test and forced swim test. The levels of the monoamine neurotransmitters including 5-hydroxytryptamine(5-HT), noradrenaline(NA) and dopamine(DA) in prefrontal cortex, hippocampus, and striatum of rats were analyzed by high performance liquid chromatography-electrochemical detection method. RESULTS: The number of rearing, time and distance of central area, sucrose preference index of mice in medium and high dose groups were decreased(P<0.05), while immobility time of forced swim test was increased(P<0.05) when compared with the mice in control group. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum decreased with the increase of 1,2-DCE exposure(P<0.05), showing a dose-effect relationship. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum in the high-dose group were lower than that of control group(P<0.05). CONCLUSION: The subacute exposure of 1,2-DCE can induce depression-like behavior in rats. The mechanism might be related to the reduction of monoamine neurotransmitters in striatum, hippocampus and prefrontal cortex.

Therapeutic progress of respiratory viral infections in children / 中国实用儿科杂志

Respiratory infections,especially respiratory viral infections,are common diseases in children. Although most respiratory viral infection diseases are self-limiting,some children may be hospitalized or even life-threatened due to severe viral lower respiratory tract infection. With the progress of virology research,new and effective antiviral drugs have been developed. Thus,the study focuses on the therapeutic progress of respiratory viral infections so as to improve the treatment for common respiratory viral infections in children.