The protective effects of disialyllacto-N-tetraose of neonatal intestinal barriers in the prevention of necrotizing enterocolitis / 中国新生儿科杂志

Objective:To study the expression of zonula occludens-1(ZO-1) in neonates with necrotizing enterocolitis (NEC) and to explore the effects of disialyllacto-N-tetraose (DSLNT), a compound extracted from human milk, on the intestinal barriers in rat model of NEC.Methods:(1) Human study: From Feb 2013 to Dec 2020, the pathological samples of ileum tissue from 21 neonates (12 patients with NEC and 9 with intestinal atresia) from Pathology Department of our hospital were collected. The expressions of ZO-1 in these samples were examined using immunohistochemistry (IHC) method. (2) Animal study: A total of 28 newborn rats were randomly assigned into control group ( n=8), NEC group ( n=10) and DSLNT+NEC group ( n=10). Experimental NEC model was established based on hypoxia (95%N 2 10 min) /cold exposure (4 ℃ 10 min) three times a day for consecutive 3 days. DSLNT+NEC group were fed with formula+DLSNT (300 μmol/L) during hypoxia/cold exposure. All the surviving rats were sacrificed at the end of the experiment (72 h) and the terminal ileum tissues were collected. Hematoxylin-Eosin (HE) staining was used to evaluate tissue damage and Western blotting was used to determine the expressions of ZO-1. (3) Cellular study: Bacterial lipopolysaccharide (LPS) was used to establish a cellular inflammation model in human intestinal epithelial cell lines (Caco-2) and DSLNT (300 μmol/L) was applied to this model. Thiazolyl blue assay was used to examine cell viabilities and immunofluorescence assay was used to detect ZO-1 expression. The effects of DSLNT on cell growth and tight junctions of Caco-2 cells were analyzed. Results:(1)Human study: The villi of mucous layer of the lesion were damaged in NEC patients. ZO-1 expressions at the epithelial junction of NEC patients were decreased compared with intestinal atresia patients and non-lesion intestines of NEC patients. (2)Animal study: Apical extrusion, necrosis and shedding of epithelial cell were seen at the lesions in NEC group. The expression of ZO-1 in NEC group was significantly lower than the control group and DSNLT+NEC group ( P<0.05).DSNLT+NEC group had higher survival rates (8/10 vs. 6/10) and lower ileum inflammatory pathological scores [2.0(1.0, 2.8) vs. 3.5(3.0, 4.0)] than NEC group. (3) Cellular study: Caco-2 cells exposed to LPS showed inhibited cell growth and decreased ZO-1 immunofluorescence staining. Caco-2 cells in the DSLNT+LPS group showed better viability than LPS group and were comparable with the control group. The expression of ZO-1 was significantly increased in the DSLNT+LPS group. Conclusions:Tight junction injury of the intestinal epithelial cell is an important characteristic of NEC. ZO-1 is a potential target for the prevention and treatment of NEC. DSLNT may protect the neonatal intestines by modulating the expression of ZO-1 and keeping tight junction integrity.

Nuclear Factor-κB Signaling Mediates Antimony-induced Astrocyte Activation / 生物医学与环境科学（英文）

Objective@#Antimony (Sb) has recently been identified as a novel nerve poison, although the cellular and molecular mechanisms underlying its neurotoxicity remain unclear. This study aimed to assess the effects of the nuclear factor kappa B (NF-κB) signaling pathway on antimony-induced astrocyte activation.@*Methods@#Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of p65. The expression of protein in brain tissue sections was detected by immunohistochemistry. The levels of mRNAs were detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR).@*Results@#Antimony exposure triggered astrocyte proliferation and increased the expression of two critical protein markers of reactive astrogliosis, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP), indicating that antimony induced astrocyte activation @*Conclusion@#Antimony activated astrocytes by activating the NF-κB signaling pathway.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Prenatal diagnosis and pedigree analysis of a case of Nail-patella syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carried out prenatal diagnosis and genetic analysis for a case with Nail-patella syndrome.@*METHODS@#Based on the clinical phenotype and prenatal imaging, genetic testing and prenatal diagnosis were carried out through whole exome sequencing (WES) and Sanger sequencing.@*RESULTS@#Analysis of amniotic fluid showed that the fetus has carried a heterozygous c.139+1G>T splicing site variant [Chr9(GRCh37): g.129376868G>T] of the LMX1B gene, which was verified by Sanger sequencing. The same heterozygous variant was found in the pregnant woman, her daughter and her mother but not in her husband. Searching of HGMD database showed that the c.139+1G>T was previously unreported.@*CONCLUSION@#Nail-patella syndrome is an autosomal dominant genetic disorder with various clinical manifestations. WES is helpful for its genetic and prenatal diagnosis.

Network pharmacology-based study on mechanisms of antipyretic action of Pueraria radix / 药学学报

This study was designed to explore the antipyretic mechanism of Pueraria radix. The method of network pharmacology was used to determine the known ingredients corresponding to Pueraria radix, predict the drug-related gene /protein targets, and analyze the interplay between key ingredients and targets. Biological Information Annotation Databases (DAVID) was used to enrich the biological processes and pathways. The result of network analysis was validated by molecular docking. It was found that 49 active ingredients of Pueraria radix not only regulate 21 targets (e.g. PTGS2, EGFR), but also affect 11 biological processes (e.g. oxidation-reduction process, prostaglandin synthesis, positive regulation of fever generation and inflammatory response) and 7 metabolic pathways (arachidonic acid metabolism, serotonergic synapse and HIF-1, et al). Molecular docking results showed that more than 65% of the active ingredients could be well docked with key targets, and the relevant literatures indicated that the active components could inhibit the expression of PTGS2, which means the result has a high reliability. These results indicated that Pueraria radix may carry its pyretic action via a "multi-ingredients-multi-targets-multi-pathways" mode, which provides a scientific basis for further research and drug development.

2,3,7,8-Tetrachlorodibenzo-p-dioxin Promotes Proliferation of Astrocyte Cells via the Akt/STAT3/Cyclin D1 Pathway / 生物医学与环境科学（英文）

OBJECTIVE@#The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant, is harmful to the nervous system, but its effects on the brain are still unclear. This study aimed to investigate the effects of TCDD on astrocytes proliferation and underlying molecular mechanism.@*METHODS@#The cell proliferation was measured by EdU-based proliferation assay and PI staining by flow cytometry. Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of signal transducer and activator of transcription 3 (STAT3).@*RESULTS@#C6 cells treated with 10 and 50 nmol/L TCDD for 24 h showed significant promotion of the proliferation of. The exposure to TCDD resulted in the upregulation in the expression levels of phosphorylated protein kinase B (p-Akt), phosphorylated STAT3, and cyclin D1 in a dose- and time-dependent manner. The inhibition of Akt expression with LY294002 or STAT3 expression with AG490 abolished the TCDD-induced cyclin D1 upregulation and cell proliferation. Furthermore, LY294002 suppressed the activation of STAT3. Finally, TCDD promoted the translocation of STAT3 from the cytoplasm to the nucleus, and LY294002 treatment blocked this effect.@*CONCLUSION@#TCDD exposure promotes the proliferation of astrocyte cells via the Akt/STAT3/cyclin D1 pathway, leading to astrogliosis.

Oxidative stress induces damage to epididymal epithelial tight junction protein ZO-1 and impairs epididymal function in varicocele rats / 中华男科学杂志

Objective@#To investigate oxidative stress-mediated damage to the epididymal epithelial tight junction protein ZO-1 and its impact on epididymal function in varicocele rats.@*METHODS@#We randomly divided 45 male adolescent SD rats into three groups of equal number: sham operation (left renal vein exposed and isolated), experimental (left renal vein constricted and collaterals of the left spermatic vein fully ligated), and treatment (60-day intragastric administration of vitamin E at 150 mg/kg/d after modeling). At 60 days after modeling, we observed the histological changes in the left epididymis, detected the expressions of ZO-1 and other tight junction-related proteins by real-time quantitative PCR, immunohistochemistry, immunofluorescence staining and Western blotting, determined sperm motility, and measured the levels of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), methylene dioxyamphetamine (MDA) and α-glucosidase (α-Glu) in the epididymal tissue of the rats.@*RESULTS@#Compared with the rats of the sham operation group, those of the experimental group showed disorganized epithelial structure and decreased number of epithelial cells in the left epididymis, with some epithelial cells desquamated into the lumen. The expression of ZO-1 was significantly lower in the experimental than in the sham operation group (P < 0.05) but markedly upregulated after VE treatment (P < 0.05). In comparison with the sham operation group, the animals in the experimental group exhibited remarkably increased content of MDA in the epididymal tissue (［0.41 ± 0.05］ vs ［1.21 ± 0.18］ nmol/mg prot, P < 0.05) but decreased levels of SOD (［814.65 ± 73.64］ vs ［298.62 ± 67.84］ U/mg prot, P < 0.05), T-AOC (［0.84 ± 0.07］ vs ［0.24 ± 0.04］ nmol/mg prot, P < 0.05) and α-Glu (［11.72 ± 2.72］ vs ［5.82 ± 1.24］ U/mg prot, P < 0.05). VE treatment, however, remarkably reduced the content of MDA (［0.69 ± 0.12］ nmol/mg prot) and elevated the levels of SOD (［497.73 ± 48.03］ U/mg prot), T-AOC (［0.42 ± 0.06］ nmol/mg prot) and α-Glu (［9.11 ± 1.91］ U/mg prot) as compared with those in the experimental group (all P < 0.05). The percentage of progressively motile sperm was significantly lower in the experimental than in the sham operation group (［31.33 ± 6.32］% vs ［71.21 ± 5.21］%, P < 0.05), but markedly increased after VE treatment (［60.68 ± 5.31］%, P < 0.05).@*CONCLUSIONS@#Varicocele reduces the expression of the EETJ protein ZO-1 and impairs epididymal function via oxidative stress, while vitamin E can effectively upregulate the ZO-1 expression and improve epididymal function by decreasing oxidative stress in the epididymis of varicocele rats.

Protective effect of urine-derived stem cells on erectile dysfunction in rats with cavernous nerve injury / 中华男科学杂志

<p><b>Objective</b>To investigate the protective effect of human urine-derived stem cells (USCs) on erectile function and cavernous structure in rats with cavernous nerve injury (CNI).</p><p><b>METHODS</b>Sixty adult male SD rats with normal sexual function were randomly divided into four groups of equal number: sham operation, bilateral CNI (BCNI) model control, phosphate buffered saline (PBS), and USC. The BCNI model was established in the latter three groups of rats by clamping the bilateral cavernous nerves. After modeling, the rats in the PBS and USC groups were treated by intracavernous injection of PBS at 200 μl and USCs at 1×106/200 μl PBS respectively for 28 days. Then, the maximum intracavernous pressure (mICP) and the ratio of mICP to mean arterial pressure (mICP/MAP) of the rats were calculated by electrical stimulation of the major pelvic ganglions, the proportion of nNOS- or NF200-positive nerve fibers in the total area of penile dorsal nerves determined by immunohistochemical staining, the levels of endothelial cell marker eNOS, smooth muscle marker α-SMA and collagen I detected by Western blot, and the smooth muscle to collagen ratio and the cell apoptosis rate in the corpus cavernosum measured by Masson staining and TUNEL, respectively.</p><p><b>RESULTS</b>After 28 days of treatment, the rats in the USC group, as compared with those in the PBS and BCNI model control groups, showed significant increases in the mICP (［81 ± 9.9］ vs ［31 ± 8.3］ and ［33 ± 4.2］ mmHg, P <0.05), mICP/MAP ratio (0.72 ± 0.05 vs 0.36 ± 0.03 and 0.35 ± 0.04, P <0.05), the proportions of nNOS-positive nerve fibers (［11.31 ± 4.22］% vs ［6.86 ± 3.08］% and ［7.29 ± 4.84］% , P <0.05) and NF200-positive nerve fibers in the total area of penile dorsal nerves (［27.31 ± 3.12］% vs ［17.38 ± 2.87］% and ［19.49 ± 4.92］%, P <0.05), the eNOS/GAPDH ratio (0.52 ± 0.08 vs 0.31 ± 0.06 and 0.33 ± 0.07, P <0.05), and the α-SMA/GAPDH ratio (1.01 ± 0.09 vs 0.36 ± 0.05 and 0.38 ± 0.04, P <0.05), but a remarkable decrease in the collagen I/GAPDH ratio (0.28 ± 0.06 vs 0.68 ± 0.04 and 0.70 ± 0.10, P <0.05). The ratio of smooth muscle to collagen in the corpus cavernosum was significantly higher in the USC than in the PBS and BCNI model control groups (17.91 ± 2.86 vs 7.70 ± 3.12 and 8.21 ± 3.83, P <0.05) while the rate of cell apoptosis markedly lower in the former than in the latter two (3.31 ± 0.83 vs 9.82 ± 0.76, P <0.01; 3.31 ± 0.83 vs 9.75 ± 0.91, P <0.05).</p><p><b>CONCLUSIONS</b>Intracavernous injection of USCs can protect the erectile function of the rat with cavernous nerve injury by protecting the nerves, improving the endothelial function, alleviating fibrosis and inhibiting cell apoptosis in the cavernous tissue.</p>

The clinical engineering strategy for reducing application risk of ventilator / 中国医学装备

Objective: To reduce the risk of ventilator in clinical use by using technical management so as to enhance cure rate for patients. Methods: Through a series of methods included of clinical investigation, statistic analysis of data, socio-technical system model and others to analyze and assess risk factors which were possibly produced in the cure process of ventilator. And the relevant risk regulation indicators were formulated as above information. Results: The formulation about risk control criterion of operation in the cure process of ventilator provided various aspects, which included of the material qualities of ventilator and breathe pipeline, clinical service environment, human factor and others, for clinical engineer to control risk so as to ensure the life safe of patients. Conclusion: The clinical engineering department should adopt technique management way to analyze the cure process of ventilator, and control risk from aspect of clinical engineering. Therefore, it can efficiently reduce the risk of ventilator in clinical application and promote the safety and efficiency of ventilator in the treatment.

Effects of resveratrol on cognitive dysfunction and the expression of parvalbumin in depression model mice / 中华行为医学与脑科学杂志

Objective To examine the antidepressant effects of resveratrol (RSV),and its possible mechanism specialized on improving cognitive function.Methods Thirty-two C57BL/6J mice were randomly divided into four groups:Control,Model,Model+RSV and Model+NA+RSV groups.The mice were subjected corticosterone (20 mg/(kg · d)) intraperitoneal injection for 21 consecutive days except the control mice.From the 22nd to 42nd day,the mice in different groups received further treatment with vehicle/ RSV (400 mg/(kg · d),op)/NA (100 mg/(kg · d),ip)+RSV (400 mg/(kg · d),op).The sugar preference test,novel object recognition test,novel location recognition test and water maze test were applied to evaluate the cognitive effects of RSV on mice.Subsequently,the silence information regulation factor 1 (SIRT1),peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α),parvalbumin (PV) transcription and translation level were evaluated by RT-PCR and Western blotting.Results The sugar preference test showed that the depression model mediated by CORT injection was successfully established(F（1,30） =6,P=0.038).In in the novel object learning test,resveratrol significantly increased the proration on the frequency ((-0.20±0.37) vs (0.16±0.29))and duration((0.10±0.45) vs (0.62±0.29)) and decreased the proration on the distance((0.09±0.36) vs (0.55±0.27)).In the water maze test,resveratrol reduced the time((41±9)s;(26± 8) s) and distance ((295± 70) cm;(224±43) cm) to find the platform.All the results were accompanied with the increased expression of protein SIRT1 (F(3,29) =15.60,P＜0.01),PGC-1α(F(3,29)=7.51,P=0.0006) and PV (F(3,29) =17.87,P=0.0004).While pretreatment with nicotinamide,resveratrol could not rescue the cognitive impairment and could not reverse the iecreased expression level of protein SIRT1,PGC-1 α and PV.Conelusion Resveratrol can reverse the cognitive dysfunction of depressant mice,which may be achieved by activating the SIRT1/PGC-1α signaling pathway and increasing the transcription and protein expression of PV.

The Value of Index of Microvascular Resistance Measured Before and Following Percutaneous Coronary Intervention in Predicting Perioperative Myocardial Infarction in Patients With Stable Coronary Artery Disease / 中国循环杂志

Objectives: This study was designed to assess whether measurement of the index of microvascular resistance (IMR) before and following percutaneous coronary intervention (PCI) could help identify patients who develop periprocedural myocardial infarction (PPMI). Methods: 54 patients with stable coronary artery disease undergoing elective PCI were divided into PPMI group and no-PPMI group. IMR and FFR was measured before and following percutaneous coronary intervention (PCI) with a pressure wire. Times of balloon inflation was also analyzed. hs-TnI at 24 h post PCI was measured. rPIMR value was calculated. Results: IMR obtained at pre-PCI and post-PCI as well as rPIMR were significantly higher in PPMI patients than in no-PPMI patients (22.02±2.92 vs 17.46±3.44, 25.86±3.04 vs 18.96±2.84, 1.22±0.21 vs 0.94±0.24, all P<0.05, respectively). Patients with PPMI more frequently underwent pre- and post-dilatation(70.8% vs 36.7%, 54.2% vs 23.3%, P<0.05), respectively, the number of balloon inflations was significantly higher in patients with PPMI than in no-PPMI patients (4.33±1.79 vs 3.20±1.63, P<0.05). The area under the ROC curve for predicting PPMI event by pre-PCI IMR was 0.941 (95%CI: 0.884-0.998, P<0.05), cut-off value was 19.91 (sensitivity: 95.8% and specificity: 77.0%). Multivariate logistic analysis showed that pre- and post-PCI IMR, rPIMR were positively correlated with PPMI (all P<0.05). Conclusions: Measuring IMR and rPIMR may allow prospective identification of patients at increased risk of PPMI.

Extraction and Separation of Boron in Anhydrite and Gypsum Minerals and Its Isotopic Measurement by Thermal Ionization Mass Spectrometry / 分析化学

The anhydrite and gypsum are the main sulfate minerals during evaporation of seawater or lake.They record the information about relative hydrogeology and the composition of mother liquor.Boron is diffluent element, and often occurs in all kinds of evaporites.Presently, the boron isotope has been applied widely in mineral deposits forming, geochemistry and palaeoenvironment.However, there is little research about characteristic of boron isotope in anhydrite and gypsum minerals, because of the low content of boron and micro-solubility in water and hydrochloric acid.This study developed a method of extracting and purifying boron in anhydrite and gypsum by phase transformation and ion-exchange.Firstly, the samples were mixed with ammonium hydrogen carbonate to transform the calcium sulfate to calcium carbonate.And diluted hydrochloric acid (1 mol/L) was added to resolve calcium carbonate.The percent conversion was about 85%in the first stage, and up to complete resolution by repeating this process.Secondly, boron specific ion-exchange resin ( Amberlite IRA 743 ) was used to gather the boron ions fully and further refined the samples with more than 1 μg of boron by anionic and cationic resin mixed by Ion Exchange Ⅱ and Dowex 50 W × 8.Finally, according to the modified method by He, the values of boron isotope were determined by TIMS.The boron content is analytically pure gypsum was 3.501 ± 0.128 μg/g ( n=12 , RSD=3.6%) and the average recovery was 100.47%.Besides, the δ11B value of analytically pure gypsum added with NIST SRM 951 was 17.98‰±0.21‰ (n=3, RSD=1.2%).This method has good repeatability and can meet the requirements of boron isotopic measurement of anhydrite and gypsum.

Patient-Specific Instruments Based on Knee Joint Computed Tomography and Full-Length Lower Extremity Radiography in Total Knee Replacement / 中华医学杂志(英文版)

<p><b>Background</b>Restoring good alignment after total knee replacement (TKR) is still a challenge globally, and the clinical efficiency of patient-specific instruments (PSIs) remains controversial. In this study, we aimed to explore the value and significance of three-dimensional printing PSIs based on knee joint computed tomography (CT) and full-length lower extremity radiography in TKR.</p><p><b>Methods</b>Between June 2013 and October 2014, 31 TKRs were performed using PSIs based on knee joint CT and full-length lower extremity radiography in 31 patients (5 males and 26 females; mean age: 67.6 ± 7.9 years; body mass index [BMI]: 27.4 ± 3.5 kg/m). Thirty-one matched patients (4 males and 27 females; mean age: 67.4 ± 7.2 years; mean BMI: 28.1 ± 4.6 kg/m) who underwent TKR using conventional instruments in the same period served as the control group. The mean follow-up period was 38 months (31-47 months). Knee Society Score (KSS), surgical time, and postoperative drainage volume were recorded. Coronal alignment was measured on full-length radiography.</p><p><b>Results</b>Twenty-three (74.2%) and 20 (64.5%) patients showed good postoperative alignment in the PSI and control groups, respectively, without significant difference between the two groups (χ= 0.68, P = 0.409). The mean surgical time was 81.48 ± 16.40 min and 72.90 ± 18.10 min for the PSI and control groups, respectively, without significant difference between the two groups (t = 0.41, P = 0.055). The postoperative drainage volume was 250.9 ± 148.8 ml in the PSI group, which was significantly less than that in the control group (602.1 ± 230.6 ml, t = 6.83, P < 0.001). No significant difference in the KSS at the final follow-up was found between the PSI and control groups (91.06 ± 3.26 vs. 90.19 ± 3.84, t = 0.95, P = 0.870).</p><p><b>Conclusions</b>The use of PSIs based on knee joint CT and standing full-length lower extremity radiography in TKR resulted in acceptable alignment compared with the use of conventional instruments, although the marginal advantage was not statistically different. Surgical time and clinical results were also similar between the two groups. However, the PSI group had less postoperative drainage.</p>

Effects of postnatal enriched environment on schizophrenia-related behaviors induced by early prena-tal polynosinic-polycytidylic acid immune challenge in adult mice offspring / 中华行为医学与脑科学杂志

Objective To investigate if the positive postnatal environment could modify the schizo-phrenia-related behaviors caused by early maternal immune activation,and the interaction of this two pre-and postnatal factors.Methods The pregnant mice were randomly divided into experimental and control groups.The experimental groups were injected with polynosinic-polycytidylic acid(Poly I : C)(5mg/kg),via intra-venous route,at gestational day 9.The control groups were injected with the same volume of normal saline (NS)at the same gestational day.All offspring were housed in groups of littermates until postnatal day (PND)21 when they were weaned.Between PND22-PND60,offspring were divided into dull or enriched en-vironment(DE or EE)groups by sex and treatment.Different toys were put into the cages of enriched envi-ronment group every week,such as running wheels,climbing materials,swings and rollers.The dull environ-ment(DE)groups were kept the normal housing environment only with sawdust.At PND60,behavioral tests were conducted,such as prepulse inhibition(PPI),open field test,novel object/location recognition,social interaction test,as well as water maze test,were conducted to evaluate the performance of all offspring.After behavioral tests,all offspring were killed and the hippocampus were dissected.The western blot was used to analyze the expression of myelin basic protein in the hippocampus.Results (1)The percentage of PPI with early maternal immune activation of Poly I : C were significantly reduced when compared with control groups (female offspring:F=28.12,P<0.001;male offspring:F=14.76,P<0.01),suggesting the schizophrenia-like behavioral deficit in the offspring induced by early prenatal Poly I : C challenge.(2)In open field test,early maternal immune activation increased the moved distance and speed of the offspring compared with the con-trol groups(female offspring:distances,F=5.10,P<0.05,speed:F=5.19,P<0.05;male offspring:distances:F=6.76,P<0.05,velocity:F=6.85,P<0.05,vs each corresponding control).(3)Enriched environment in-creased the social interaction time of offspring with strange mouse in the social interaction test(female off-spring:EE group(101.30±6.83)s,DE group(76.50±5.59)s,F=9.41,P<0.01;male offspring:EE group(98. 52±6.82)s,DE group(75.82±3.95)s,F=7.95,P<0.01).(4)Enriched environment decreased the time for offspring to find the platform in water maze test(P<0.05).(5)The expression of myelin basic protein in hip-pocampus in offspring which received early maternal immune activation by Poly I : C was lower than that in the control groups(P<0.05).Conclusion The postnatal enriched environment increased the social interac-tion and the learning abilities of the offspring with early maternal immune activation by Poly I : C in water maze,and even more improved the perseveration behavior of the offspring induced by the early maternal im-mune activation.

Comparison of Conbercept with Ranibizumab for the treatment efficiency of macular edema:a meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To study the clinical effect of Conbercept and Ranibizumab for macular edema ( ME ) with meta -analysis.·METHODS:We searched Pubmed, EMBASE, Cochrane Library Central Register of Controlled Trials ( CENTRAL) , Google scholar, ClinicalTrials. gov, CNKI, VIP and wanfang database for studies which published between January 12012 and July 12017, on the comparison of conbercept with ranibizumab for the clinical effect of secondary macular edema. The primary endpoints were visual acuity ( VA ) and central macular thickness in this study to assess the efficiency of the drugs. Review Manager 5. 3 and Stata 12. 0 were used for data analysis with the pooled odds ratios (OR), mean difference and 95% confidence interval ( CI) .·RESULTS: Eleven RCTs involving 812 patients met inclusion criteria and included in this meta-analysis, including 414 eyes in conbercept group and 398 eyes in ranibizumab group. Macular edema in this study were secondary to age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. No significant differences in improvement of vision acuity(P=0. 09) or reduction of CMT (P>0. 05) were noted at the end of 3mo between two groups. Compared to ranibizumab, conbercept showed a better effectiveness in macular edema alleviation in the end of 6mo in the present study (OR=-58. 50, 95%CI: -108. 04 to -8. 95;P=0. 02).· CONCLUSION: Despite evidence from the meta -analysis of the RCTs suggesting a strong difference of the effectiveness for macular edema between conbercept and ranibizumab, more clinical trials are still needed to confirm our results because of the heterogeneity in the collected data.

Establishment of Mouse Model of H-2 Haploidentical Hematopoietic Stem Cell Transplantation from Double Donors / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish a new mouse model of H-2 haploidentical stem cell transplantation from double donors (DHSCT) and compare with conventional haploidentical hematopoietic stem cell transplantation (HSCT) so as to alleviate transplant-related complications.</p><p><b>METHODS</b>The recipients CB6F1 of conventional HSCT group were pretreated by 8 Gy total body irradiation(TBI), and received 3×10donor (male C57) spleen mononuclear cells (spMNC) mobilized by G-CSF within 2 hours after TBI. Recipients CB6F1 of D-HSCT groups accepted 2 Gy TBI, and received total 12×10spMNC mobilized by G-CSF from 2 donors within 2 hours after TBI, each donor donated 6×10cells. According to the different strains and sex of donors, DHSCT were divided into 3 groups: in group A, the stem cells were from male C57 and female BALB/c; in group B, stem cells were from male C57 and male BALB/c, while the stem cells in group C were from male C57 and male C3H. Hematopoietic reconstruction, engraftment, GVHD and survival were observed among these 4 groups.</p><p><b>RESULTS</b>The nadir of white blood cell count after conventional HSCT were lower than 1×10/L and lasted for 3 to 5 days, while not less than 3×10/L after D-HSCT among either group A, B or C. The complete chimerism (CC) in conventional HSCT group was achieved quickly within only 1 week in peripheral blood. Mixed chimerism (MC) in peripheral blood was found within the first week after DHSCT among either group A, B or C, and transformed into stable CC within the second week eventually. Both GVHD morbidity and mortality of conventional HSCT were 100% at 34th day after transplantation.Among DHSCT groups,the overall GVHD morbidity and mortality at 34th day after transplant were 49.6% and 50%(P<0.01,P<0.05), respectively,and 60.4% and 81.2% at 50th day after transplant. Overall survival of 50 days was 50.9% that indicated a long survival in such mice DHSCT. The differences of hematopoietic reconstruction, donor cell engraftment, GVHD incidence, GVHD mortality and OS were not statistically significant among group A, B and C(P>0.05).</p><p><b>CONCLUSION</b>A new mouse model of H-2 haploidentical peripheral blood stem cell transplantation from double donors (DHSCT) has been successfully established by reducing conditioning intensity and increasing graft cell numbers from double haploidentical donors without GVHD prophylaxis. DHSCT successfully achieved stable complete chimerism, less GVHD morbidity and mortality and longer OS without hematopoietic suppression. This study provides experimental evidence for clinical application of HLA haploidentical peripheral blood stem cell transplantation from double donors.</p>

Biological Characteristics of Microvesicles Secreted by Human Peripheral Blood Hematopoietic Stem Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of microvesicles(MV) isolated from human peripheral blood hematopoietic stem cells(PB-HSC) on immune regulation and hematopoiesis.</p><p><b>METHODS</b>PB-HSCs were separated by density-gradient centrifugation and cultrued. The supernatants of PB-HSC at 48 h were harvested for isolation and purification of MV by using ultracentrifugation. The electron microscopy was used to observe the morphology of MV. The protein level in MV was quantified through bicinchoninic acid(BCA) protein assay. Flow cytometry was used to detect the immunophenotype of MV. Human peripheral blood mononuclear cells(PB-MNC) were isolated from healthy donor and treated with isolated MV. After being co-cultured for 12 h, confocal microscopy was used to observe the action mode of MV on PB-MNC. After being co-cultured for 48 h, the levels of IL-2, IL-6, IL-8, IL-10, IFN-γ and TNF-α were detected by ELISA. Flow cytometry was used to detect the changes of T cell subsets and the activation of T cell subsets as well as intracellular cytokine staining after co-culture for 48 h. The methylcellulose was used to assess the hematopoiesis-supportive function of MV as well as co-cultured supernatants.</p><p><b>RESULTS</b>The eletron microscopy revealed that MV were elliptical membrane vesicles. The protein amount in MV ranges from 29 to 110 µg. Flow cytometry showed that MV expressed mix markers on the surface, especially highly expressed MV specific marker CD63(85.86%) and hematopoietic stem cell marker CD34(33.52%). After being co-cultured for 12 h, confocal microscopy showed that MV were merged with PB-MNC. After being co-cultured for 48 h, ELISA showed that the secretion of cytokines IL-6,IL-8, IL-10 as well as TNF-α was increased while the level of IL-2 and IFN-γ was not changed much. The results of flow cytometry showed that there was no significant change in T cell subsets and T cell activation. Staining of intracellular factor showed that IL-8 was increased significantly in CD11ccells. The colony-forming experiments revealed that MV and the co-cultured supernatants could facilitate the colony formation.</p><p><b>CONCLUSION</b>MV isolated from PB-HSC have immune-regulatery function and can prornote hematopoiesis.</p>

Effect of Infusion of Recipient Spleen Cells at Different Time after Murine Haploidentical Hematopoietic Stem Cell Transplantation on Graft Versus Host Disease / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of infusing G-CSF mobilized recipient spleen cells at different time after haploidentical stem cell transplantation(HSCT) on graft-versus-host disease (GVHD) in mice and its possible mechanism.</p><p><b>METHODS</b>Forty mice after HSCT were randomly divided into 4 groups (n=10): GVHD positive control group (control group), 1st d recipient cell infusion group after transplantation (+1 d group), 4th d recipient cell infusion group after transplantation(+4 d group), 7th d recipient cell infusion group after transplantation(+7 d group). The mice in control group were injected the normal saline of same equivalent with experimental group which were given the same amount of G-CSF-mobilized recipient spleen cells. The general manifestation and pathological change of GVHD were observed. The expression changes of CD3CD4, CD3CD8cell subsets and FasL in peripheral blood were detected by flow cytometry.</p><p><b>RESULTS</b>The incidence of GVHD was significantly decreased in +4 d group and the median survival time was longer than 60 days, which was significantly higher than that of control group (24 d), +1 d group (21 d), +7 d group (28 d). (P<0.01, P<0.01, P<0.01). The Fasl expression of peripheral blood T lymphocytes in +4 d group were significantly lower than that in the other 3 groups(P<0.05).</p><p><b>CONCLUSION</b>The +4 d infusion of G-CSF mobilized recipient spleen cells on 4th day after haploidentical HSC transplantation can inhibit the expression of FasL in donor T lymphocytes, and significantly reduce the incidence of GVHD.</p>

Significance of Monitoring Minimal Residual Disease by Flow Cytometry in Acute Leukemia Patients Underwent Nonmyeloablative Allo-HSCT / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the value of dynamically monitoring minimal residual disease (MRD) by flow cytometry before and after non-myeloablative allo-HSCT (NST) for prediction of acute leukemia(AL) relapse after transplantation.</p><p><b>METHODS</b>The clinical data of 51 AL patients underwent NST were analyzed retrospectively in Department of Hematology of Affiliated Hospital of Academy of Military Medical Sciences from January 2011 to December 2015. All AL patients achieved the morphologic complete remission of bone marrow before transplantation. The bone marrow samples were collected for monitoring of MRD within 35 days before transplant, every month till 3 months after transplant, every 3 months till 24 months after transplant, and then every 6 months after 2 years of transplant. According to the MRD cutoff value of 0.2%, the AL patients were divided into high level MRD group (18 cases) which was defined as MRD≥0.2% after transplantantion at least for 1 time, and low level MRD group (33 cases) which was defined as MRD<0.2% after transplant all the time. 2 year cumulative relapse rate in 2 groups were compared.</p><p><b>RESULTS</b>Two-year relapse rates were 6.1% and 50% in low-level MRD group and high-level MRD group post NST(P=0.001)respectively. Multivariate analysis indicated that the risk of relapse in high level MRD group was 5.84 times of low level MRD group(P=0.036). MRD≥0.2% post transplant was an independent risk factor for leukemia relapse post NST. The mortality rate was 81.8% and 46.3%(P<0.05) in relapse and non-relapse groups respectively.</p><p><b>CONCLUSION</b>Dynamically monitoring MRD by FCM is a crucial tool for early relapse estimation of acute leukemia in adult patients after allogeneic nonmyeloablative hematopoietic stem cell transplantation. MRD≥0.2% after transplant can be used as a early valuable evidence for predicting relapse and guiding active medical intervention.</p>

Biological characteristics of Microvesicles Derived from Bone Marrow Mesenchymal Stem Cells and Their Capacities Supporting ex vivo Expansion of Hematopoietic Stem Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the biological characteristics of microvesicles(MV) derived from bone marrow mesenchymal stem cells (BM-MSC) and their capability supporting ex vivo expansion of hematopoietic stem cells(HSC).</p><p><b>METHODS</b>The MV from cultured BM-MSC supernatant were isolated by multi-step differential velocity contrifugation; the morphological characteristics of MV were observed by electron microscopy with negative staining of samples; the protein level in MV was detected by using Micro-BCA method; the surface markers on MV were analyzed by flow cytometry. The peripheral blood HSC(PB-HSC) were isolated after culture and mobilization; the experiment was diveded into 2 group: in MV group, the 10 mg/L MV was given, while in control group, the same volume of PBS was given; the change of PB-HSC count was observed by cell counting; the change of surface markers on PB-HSC was detected dynamically by flow cytometry; the cell colony culture was used to determin the function change of PB-HSC after co-culture with MV.</p><p><b>RESULTS</b>MSC-MVs are 20-100 nm circular vesicles under electron microscope. About 10 µg protein could be extracted from every 1×10MSC. The flow cytometry showed that CD63 and CD44 were positive with a rate of 96.0% and 50.2%, while the HLA-DR, CD34, CD29 and CD73 etc were negative. When being co-cultured with GPBMNC for 2 days, the cell number of MV groups was 1.49±0.15 times of the control group (P>0.05). When being co-cultured for 4 days, the cell number of MV groups was 2.20±0.24 times of the control group(P<0.05). The CD34cell number of MV groups was 1.76±0.30 times the control group after culture for 2 day and 1.95±0.20 times after culture for 4 day.</p><p><b>CONCLUSION</b>The MV has been successfully extracted from MSC culture supernatant by multi-step differential velocity centrifugation. MSC-MV can promote HSC expansion in vitro.</p>