Bone microarchitecture impairment in prolactinoma patients assessed by HR-pQCT.

PURPOSE: Prolactinoma may reduce bone mineral density (BMD) and increase fracture risk, but its influence on bone microarchitecture remains to be elucidated. The purpose of this study is to evaluate bone microarchitecture parameters by high-resolution peripheral quantitative computed tomography (HR-pQCT) in prolactinoma patients. METHODS: 31 prolactinoma patients and 62 age- and sex-matched healthy controls in our center were included, and HR-pQCT was used to evaluate their bone microarchitecture at the radius and tibia. Z-scores for bone microarchitecture parameters were calculated based on previously published reference. RESULTS: After adjusting for height and weight, prolactinoma patients had lower trabecular (- 0.011 mm, p = 0.005) and cortical thickness (- 0.116 mm, p = 0.008) and cortical area (- 6.0 mm2, p = 0.013) at radius, as well as lower trabecular (- 0.014 mm, p = 0.008) and cortical (- 0.122 mm, p = 0.022) thickness at tibia compared with the controls. Patients with higher prolactin level had more severe bone microarchitecture impairments. After adjusting for prolactin level and age, male patients had lower trabecular volumetric BMD (vBMD), trabecular number, trabecular thickness, and cortical porosity at radius, as well as lower trabecular vBMD, trabecular bone volume fraction, trabecular number, and cortical area, and higher trabecular separation at tibia compared with female patients. Z-score for radius vBMD was correlated with Z-score for areal BMD (aBMD) at lumbar and femoral neck, while Z-score for tibia vBMD was correlated with Z-score for lumbar aBMD, and some patients with vBMD Z-score below - 2.0 had aBMD Z-score within normal range. CONCLUSION: Peripheral bone microarchitecture was impaired in prolactinoma patients, especially in patients with higher prolactin level. We compared the bone microarchitecture of prolactinoma patients and healthy controls by high-resolution peripheral quantitative computed tomography (HR-pQCT), and found that many bone microarchitecture parameters were impaired among prolactinoma patients. Such impairment was more prominent among patients with higher prolactin level.

Pregnancy outcome after in-vitro fertilization/intracytoplasmic sperm injection in women with congenital uterus didelphys.

OBJECTIVE: To investigate the pregnancy and obstetric outcomes of patients with congenital uterus didelphys who achieved clinical pregnancy after in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: This was a retrospective matched-cohort study of 83 infertile patients with uterus didelphys who underwent IVF/ICSI and achieved clinical pregnancy from January 2005 to December 2018 at our center. For each patient in the study group, three control patients with normal uterine morphology who underwent IVF/ICSI in 2018 were selected randomly. Patients in the two groups were matched for number of gestational sacs, maternal age, infertility type, cause of infertility, fertilization method, endometrial thickness 1 day before embryo transfer and number of embryos transferred. The classification of congenital uterine anomalies was based on the American Fertility Society system (1988). The pregnancy and obstetric outcomes of the didelphic and control groups were compared separately for singleton and twin pregnancies, and for all pregnancies combined. RESULTS: In singleton pregnancies, women with uterus didelphys had increased risk of preterm birth (odds ratio (OR), 4.68; rate difference (RD), 0.14; P < 0.001), Cesarean section (OR, 2.80; RD, 0.17; P = 0.016) and birth weight < 2500 g (OR, 4.06; RD, 0.10; P = 0.017) compared to women with normal uterine morphology. In twin pregnancies, the presence of uterus didelphys was associated with increased risk of preterm delivery (OR, 4.79; RD, 0.37; P = 0.006), perinatal mortality (OR, 3.16; RD, 0.19; P = 0.043) and birth weight < 2500 g (OR, 9.57; RD, 0.35; P = 0.001). CONCLUSIONS: The presence of uterus didelphys was associated with significantly increased risk of some adverse pregnancy outcomes compared to pregnancies with normal uterine morphology in women who underwent IVF/ICSI. A twin pregnancy in women with uterus didelphys was associated with worse perinatal outcome. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

A study on serum pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG) levels in patients with acromegaly.

PURPOSE: Acromegaly caused by growth hormone cell adenoma is commonly associated with abnormal glucolipid metabolism, which may result from changes in adipocytokine secretion. This study aims to investigate serum adipokine levels, including pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG), in acromegalic patients and the correlation between the levels of these three adipokines and GH levels and glucolipid metabolism indices. METHODS: Sixty-eight acromegalic patients and 121 controls were included, and their clinical data were recorded from electronic medical record system. Serum PNT, furin and ZAG levels were measured by ELISA. RESULTS: Serum PNT levels in acromegalic patients were significantly higher than controls (66.60 ± 12.36 vs. 46.68 ± 20.54 pg/ml, P < 0.001), and acromegaly was an independent influencing factor of PNT levels (P < 0.001). Moreover, subjects with the highest tertile of PNT levels had a close correlation with acromegaly (OR = 22.200, 95% CI 7.156 ~ 68.875, P < 0.001), even in Model 1 adjusted for gender and age and Model 2 adjusted for gender, age and BMI. Additionally, serum PNT levels were positively correlated with BMI (r = 0.220, P = 0.002) and triglycerides (TGs, r = 0.295, P < 0.001), and TGs were an independent influencing factor of serum PNT levels in acromegalic subjects (P < 0.001). Furthermore, serum PNT levels in obese acromegalic patients were significantly higher than those with normal BMI (P < 0.05). However, serum furin levels were lower in acromegalic patients than controls (0.184 ± 0.036 vs. 0.204 ± 0.061 ng/ml, P < 0.001). CONCLUSION: This study is the first to demonstrate that acromegalic patients have increased serum PNT levels. Moreover, serum PNT plays a potential role in abnormal lipid metabolism of acromegalic patients.

Serum glypican4 and glycosylphosphatidylinositol-specific phospholipase D levels are associated with adipose tissue insulin resistance in obese subjects with different glucose metabolism status.

OBJECTIVES: Glypican4 (GPC4) is a novel adipokine associated with obesity and insulin resistance. GPC4 was cleaved by the glycosylphosphatidylinositol-specific phospholipase D (GPLD1) in an anchored site of the glycosylphosphatidylinositol, and then was released into the extracellular environment. Herein, we investigated the changes of serum GPC4 and GPLD1 levels in obese subjects with different glucose metabolism status and their relationship with adipose tissue insulin resistance index (Adipo-IR) in Chinese north populations. METHODS: A total of 221 obese subjects and 37 normal controls (NC) were recruited in this study. Obese subjects were divided into normal insulin (NI) group, hyperinsulinemia (HI) group, impaired glucose tolerance (IGT) group, and type 2 diabetes mellitus (DM) group. Serum GPC4, GPLD1, and adiponectin were determined by commercially available ELISA kits. RESULTS: Serum GPC4 levels in the HI, IGT, and DM groups were significantly higher than those in the NC and NI groups (2.27 ± 0.58 ng/mL, 2.21 ± 0.60 ng/mL, 2.49 ± 0.67 ng/mL vs. 1.70 ± 0.33 ng/mL, 1.93 ± 0.34 ng/mL, P < 0.05). GPC4 was positively correlated with GPLD1, which was the most important influencing factor of GPC4. Adipo-IR was independently and positively associated with serum GPC4 and GPLD1. For GPC4, after adjustment for confounders, the risk of adipose tissue insulin resistance in subjects with the highest tertile was 2.974-fold that of those with the lowest tertile (OR = 2.974, P = 0.013). For GPLD1, before adjustment for lipids, the increased probability still existed (Model 2, OR = 3.568, P = 0.003). CONCLUSION: GPC4 is an adipokine associated with adipose tissue insulin resistance, and its activity may be regulated by GPLD1. GPC4 may be a marker for adipose tissue insulin resistance in Chinese north obese populations.

[Effects of orlistat and metformin on metabolism and gonadal function in overweight or obese patients with polycystic ovary syndrome].

The aim of this study was to assess the effects of orlistat or metformin treatment on lipid and glucose metabolism, and gonadal function in obese/overweight women with polycystic ovary syndrome (PCOS). A total of 39 patients diagnosed with PCOS were randomly (digital table method) divided into orlistat treatment group (20 cases) and metformin treatment group (19 cases). Compared with those before, treatment with either orlistat or metformin significantly reduced body weight, body mass index (BMI), hip circumferences, and serum insulin levels of the PCOS patients both at the end of 3 months and 6 months (P<0.05). No significant differences could be viewed between orlistat and metformin treated subjects. Moreover, orlistat treatment significantly lowered the levels of low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) (P<0.05), while there were no significant changes in above parameters with metformin treatment. The improvement of menstrual cycle was observed after 6-month treatment in both groups (P<0.05). However, changes in polycystic ovarian morphology by ultrasound were only observed in orlistat treated group. In conclusion, orlistat is comparable with metformin in weight loss and improvement of insulin resistance and menstrual cycle, and is superior to metformin in improvement of lipid metabolism in overweight/obese PCOS patients.

[Changes in platelet related parameters in obese patients after sleeve gastrectomy].

To compare changes in platelet related parameters in obese patients before and after sleeve gastrectomy (SG), we retrospectively analyzed the clinical data of 31 obese patients who underwent SG in Peking Union Medical College Hospital from December 2012 to September 2020. Results showed that compared with those before surgery, platelet count (PLT) decreased significantly at 2-12 weeks of follow-up (P=0.009), while platelet distribution width (PDW), mean platelet volume (MPV), and large platelet ratio (P-LCR) increased significantly at the same periods of follow-up after operation (P<0.001). However, the levels of PDW, MPV, and P-LCR began to decrease at 16-55 weeks when compared with those at 2-12 weeks of follow-up (P<0.01). PLT was positively correlated with white blood cells and neutrophils at 2-12 weeks of follow-up and positively correlated with high sensitivity C-reactive protein at 16-55 weeks of follow-up after operation (P<0.05).

Effect of insulin-like growth factor-1 on promoting healing of skin ulcers in diabetic rats.

To investigate the effect of exogenous insulin-like growth factor-1 (IGF-1) on the healing of skin ulcers in diabetic rats, male Sprague Dawleys (SD) rats with back skin ulcers were selected and divided into control group, model group and IGF-1 treatment group which received different doses of IGF-1 (0.5, 1.0, 1.5, and 2.0mg/L). The results showed that the healing speed of the skin ulcers was significantly affected by IGF-1, which reduced the size of wound (P less than 0.05). The expression of MMP-9 was enhanced while the expression of TIMP-1 was decreased in diabetic rats with skin ulcers. The IGF-1 treatment helped to re¬store the normal expression of both MMP-9 and TIMP-1 in diabetic rats with skin ulcers, and diabetic skin ulcers in the 1.5 mg/L IGF-1 group showed the best healing. Histological examination showed that after 20 days, fibroblasts in the IGF-1 experimental group with an appropriate concentration increased and the numbers of fibroblasts and capillaries were significantly higher than those of the other groups. Moreover, there were obvious wound surface contractions and re-epithelialization, and the new epithelium moved to the center of the wound faster. Therefore, it is concluded that an appropriate concentration of IGF-1 can significantly promote the healing of skin ulcers in diabetic rats.

Identification of Tiletamine, Zolazepam and Their Metabolites in Drug Facilitated Sexual Assault by GC-QTOF-MS.

ABSTRACT: Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry （GC-QTOF-MS）. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.

Whole-exome sequencing identifies a homozygous donor splice-site mutation in STAG3 that causes primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is the depletion or loss of normal ovarian function, which cause infertility in women before the age of 40 years. Two homozygous germline truncation mutations in STAG3 gene had been reported to causes POI in consanguineous families. Here, we aimed to identify the genetic cause of POI in 2 affected sisters manifested with primary amenorrhea and partial development of secondary sexual characters with normal range of height of a consanguineous Han Chinese family. Whole-exome and Sanger sequencing identified a homozygous donor splice-site mutation (NM_012447.2: c.1573+5G>A) in the STAG3 gene. RT-PCR revealed that the mutation causes loss of wild-type donor splice-site which leads to aberrant splicing of STAG3 mRNA and consecutive formation of STAG3 alternative transcript (p.Leu490Thrfs*10) . This is the first report of splice-site mutation of STAG3 gene causes POI in 2 Han Chinese patients.

[Relationship between UGT1A1 gene polymorphisms and irinotecan-induced severe adverse events].

Objective: To investigate the relationship between UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 polymorphisms and irinotecan-induced severe adverse reactions(grade 3-4 delayed diarrhea and neutropenia) in Chinese cancer patients. Methods: A total of 141 cancer patients treated with irinotecan were enrolled in this study. Peripheral venous blood was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 were analyzed by PCR and direct sequencing. The adverse reactions during chemotherapy were observed and recorded. The incidence of severe adverse reactions was compared among patients with different genotypes. Results: Among 141 patients, the cases with UGT1A1*6 GG, GA and AA genotypes were 71, 54 and 16, while those with UGT1A1*28 TA6/6, TA6/7 and TA7/7 genotypes were 105, 33 and 3, respectively. The cases with UGT1A1*60 AA, AC and CC genotypes were 52, 80 and 9, while those with UGT1A1*93 GG, GA and AA genotypes were 105, 32 and 4, respectively. The patients with grade 3-4 delayed diarrhea and neutropenia were 23 and 56, respectively. Multivariate logistic regression analysis showed that UGT1A1*6 and UGT1A1*60 genetic polymorphisms were independent factors influencing the occurrence of grade 3-4 delayed diarrhea. The risk of grade 3-4 delayed diarrhea in homozygous AA carriers of UGT1A1*6 increased 3.79 times compared with that in wild-type GG carriers (95%CI: 1.35-10.67). Moreover, the risk of grade 3-4 delayed diarrhea in homozygous CC carriers of UGT1A1*60 was 20.42 times compared with that in wild-type AA carriers (95%CI: 3.52-118.33). In addition, UGT1A1*28 genetic polymorphism was an independent factor of the occurrence of grade 3-4 neutropenia. The patients with homozygous TA7/7 carriers of UGT1A1*28 had an 1.61 times higher risk of grade 3-4 neutropenia compared with those with wild-type TA6/6 carriers (95%CI: 1.44-12.65). There was no correlation between UGT1A1*93 genetic polymorphism and severe adverse reactions caused by irinotecan. Conclusion: The cancer patients who carried UGT1A1*6, UGT1A1*28 and UGT1A1*60 gene polymorphisms have high risk of severe adverse events caused by irinotecan-based chemotherapy.

[A survey of fluid therapy in 2 intensive care units].

To explore the present status of fluid therapy and clinical outcome in critically ill patients in intensive care units (ICU). ICU patients consecutively admitted to our ICU were prospectively enrolled. Patients' demographics, laboratory data, fluid record and clinical outcome were collected. Fluid intake quantity of all patients was at peak on the fifth day which was 2 806 (1 997, 3 582) ml. From the fourth day in ICU, fluid balance started to benegative as -84 (-1 127, 612) ml and gradually increased. Crystalloid solution was the main components. For treatment purposes, medication injections and nutrients were major fluids. Positive correlations were found between total fluid intake quantity, total crystalloid volume, total colloidal volume and hospital stay, ICU stay, duration of intubation (r values as 0.211, 0.686, 0.282, 0.155, 0.506, 0.174, 0.209, 0.072, 0.292, respectively P<0.05). Moreover, positive correlations were also demonstrated between total colloidal volume and total bilirubin, direct bilirubin, alanine transaminase, aspartate transaminase, blood urea nitrogen, serum creatinine (r values as 0.196, 0.242, 0.190, 0.335, 0.284, 0.223, respectively P<0.05).

[Effects of sural nerve nutrition vess els-supported flap for reconstruction of distal lower leg and ankle soft tissue defects].

Objective: To observe the effects of sural nerve nutrition vessels-supported flap for reconstruction of distal lower leg and ankle soft tissue defects. Methods: From June 2014 to June 2017, 37 patients with calf distal and ankle soft tissue defect were repaired with sural nerve nutrition vessels-supported flap, of them 12 cases with calf distal soft tissue defect wounds and 25 cases with ankle soft tissue defect wounds.The scope of flaps was 9 cm×4 cm to 18 cm×9 cm, anti-infection, anti-freezing and dressing treatments were carried out after operation.The results of two-point discrimination among reexamination were recorded. Results: All the flaps survived without ulcer and effusion, only 1 flap for reconstruction of medial malleolus swelled and deactivated at the beginning while it recovered with proper dressings.During the follow-up periods, all the flaps kept favorable feelings, aspects and functions, and the two-point discrimination was 5 to 15 mm [averaged (11.2±1.7) mm]. Conclusion: Sural nerve nutrition vessels-supported flap brings significant effects with excellent safety and reliability in repairing calf and ankle soft tissue defects.

Time-lapse observation and transcriptome analysis of a case with repeated multiple pronuclei after IVF/ICSI.

PURPOSE: The purpose of this study was to investigate the cause of repeated multipronucleus (MPN) formation in zygotes in a patient after both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). METHOD: This is a case study. A patient had unexplained primary infertility with recurring total MPN zygotes after IVF and ICSI cycles. Time-lapse monitoring of pronucleus formation was carried out. Embryos developed from MPN zygotes were analyzed by fluorescence in situ hybridization (FISH). Single-cell RNA-seq analysis was used to identify gene expression profiles of the patient's oocyte and zygote, and these were compared to the data from oocytes and zygotes from donors with normal fertilization (patient, n = 1; donors, n = 4). Oocyte-specific genes with differential expression were selected by the Amazonia! RESULTS: From time-lapse analysis, we observed the formation of multiple micronuclei near the site of the second polar body extrusion. These micronuclei migrated, expanded, and juxtaposed with the male pronucleus leading to a multipronucleus. None of these MPN zygotes could develop to the blastocyst stage, and FISH analysis revealed a chaotic chromosomal complement in the arrested embryos. RNA-seq analysis showed 113 differentially expressed genes (DEGs) between the patient and the donor oocytes and zygotes. Moreover, 25 of the 113 DEGs were unique or highly expressed in oocytes and early embryos. From 25 DEGs, three genes, DYNC2LI1, NEK2, and CCNH, which are involved in meiosis and the chromosome separation process, were further validated by real-time PCR. CONCLUSION: We identified several candidate genes affecting pronucleus formation as a new cause of infertility.

[Effect of astaxanthin on vascular smooth muscle cells proliferation induced by platelet derived growth factor-BB].

OBJECTIVE: To investigate the effect of astaxanthin (AST) on vascular smooth muscle cells (VSMCs) proliferation in vitro induced by platelet derived growth factor-BB (PDGF-BB), and to explore its possible mechanism. METHODS: There were 4 groups in this experiment: blank control group, PDGF-BB group, PDGF-BB+ AST group, AST group. After the cells received different intervention for the indicated time, the cell growth was determined by Trypan blue staining; cell proliferation was demonstrated using CCK-8 kit; the cell cycle progression was analyzed by flow cytometry, and the mRNA expression of cyclin D1, cyclin E, CDK6, CDK4, cyclin kinase inhibitor protein P21 was determined by real-time PCR; reactive oxygen species (ROS) generation was detected using a Microplate reader; the total and phosphorylated forms of ERK1/2, p38 MAPK, JNK was observed in AST pretreated VSMCs in 5, 10 and 15 min after PDGF-BB treatment by Western blot analysis. RESULTS: (1) Cell viability: AST and/or PDGF-BB did not induce VSMCs necrosis with the different concentration compared with untreated cells (P>0.05). (2) Cell proliferation: PDGF-BB induced VSMCs proliferation (2.5±0.3 vs 1, P<0.01), while AST reversed the effect in a concentration-dependent manner when co-treated with PDGF-BB (all P<0.01); Cell cycle: Flow cytometry analysis showed that AST at a dose of 25 µmol/L reduced the percentages of cells in S phase and increased the G0/G1 populations in PDGF-BB-stimulated VSMCs; mRNA expression of the check-point proteins: Real Time PCR results demonstrated that, compared with the control group, the mRNA expression of CDK6, CDK4, cyclin D1, cyclin E in the PDGF-BB group was higher (4.20±0.30, 2.90±0.18, 3.50±0.30, 2.70±0.11 vs 1, all P<0.01), while p21 mRNA expression was lower (0.52±0.03 vs 1, P<0.01), while AST reversed these effects when co-treated with PDGF-BB. (3) ROS expression: compared with the control group, ROS level was significantly higher in the PDGF-BB group (2.10±0.09 vs 1, P<0.01), while AST reversed the effect in a concentration-dependent manner when co-treated with PDGF-BB (all P<0.01). (4) Signaling pathway: AST blocking the proliferation of VSMCs induced by PDGF-BB was related to suppress ERK1/2, p-p38 MAPK signaling pathway, but little effect to JNK. Conclutions: These results demonstrate that AST can block the proliferation and migration of VSMCs through G0/G1 to S phase of the cell cycle arrest. Further study indicates that AST suppress PDGF-BB-induced VSMCs proliferation is associated with an inhibition of ROS generation and ERK1/2, p-p38 MAPK signal pathways.

[Comparison of efficacy between the serum cortisol and 24 hour urine free cortisol in combined dexamethasone suppression test in the diagnosis of Cushing syndrome].

OBJECTIVE: To compare the sensitivity and specificity between the 24 hour urine free cortisol (24 h UFC) and serum cortisol in dexamethasone suppression test (DST) in the diagnosis of Cushing syndrome (CS). METHODS: Combined low dose DST (LDDST) and high dose DST (HDDST) were carried out in 67 cases of CS with surgically confirmed cases in recent 3 years(from January 2011 to November 2015). The serum cortisol and 24 h UFC were collected simultaneously for each subject and the sensitivity and specificity of serum cortisol and 24 h UFC were compared. RESULTS: There were Cushing disease (CD) group (n=53), ectopic adrenocorticotropic hormone (ACTH) syndrome group (n=7) and ACTH-independent Cushing syndrome group (n=7) according to the etiology of hypercorticordism.There were no significant differences among 3 groups in gender and age.The sensitivity of serum cortisol of different cut off points(50, 110, 140 nmol/L and 50% of control)after LDDST was 97.01%, 86.57%, 83.58% and 70.15% respectively.Meanwhile, the sensitivity of cutoff point of 24 h UFC <32 nmol in combined LDDST was 92.54% in the diagnosis of Cushing syndrome.There was no significant differences in two groups between serum cortisol <110 nmol/L and 24 h UFC <32 nmol.However, the sensitivity of serum cortisol <50 nmol/L was significantly higher than 24 h UFC<32 nmol (P<0.05). Furthermore, in combined HDDST, if the suppression rate was ≥50%, the sensitivity of serum cortisol and 24 h UFC in differentiating the etiology of Cushing disease was 60.38% and 90.57%, and the specificity was 91.43% and 96.00% respectively.There were significant differences between serum cortisol and 24 h UFC in both of sensitivity and specificity (both P<0.05). In addition, if the suppression rate of 24 h UFC in HDDST was adjusted to 60.85% according to receiver operating characteristic (ROC) curve, it could have the best levels of sensitivity (92.6%) with the specificity of 85.7%. If the suppression rate of serum cortisol was adjusted to 61.53% in HDDST according to ROC curve, it could have the best sensitivity (64.8%) with the specificity of 78.6% accordingly. CONCLUSION: In combined LDDST, the serum cortisol <50 nmol/L had a higher sensitivity than the 24 h UFC<32 nmol when they were used as the criteria in determining the diagnosis of CS.In HDDST, the sensitivity and specificity of suppression rate of 24 h UFC ≥50% were better than serum cortisol to differentiate the etiology of CS.

Blockade of Extracellular HMGB1 Suppresses Xenoreactive B Cell Responses and Delays Acute Vascular Xenogeneic Rejection.

Blockade of extracellular high mobility group box 1 (HMGB1) can significantly prolong murine cardiac allograft survival. Here, we determined the role of HMGB1 in xenotransplantation. Sprague-Dawley rat hearts were transplanted heterotopically into BALB/c mice. Xenografts without any treatment developed predominant acute vascular rejection within 6 days. Both passively released HMGB1 from xenografts and actively secreted HMGB1 from infiltrated immune cells were significantly increased after xenotransplantation. HMGB1-neutralizing antibody treatment significantly prolonged xenograft survival and attenuated pathologic damage, immune cell infiltration, and HMGB1 expression and release in the xenografts. Compared to control IgG treatment evaluated at study endpoint, treatment with HMGB1-neutralizing antibody markedly suppressed xenoreactive B cell responses, as evidenced by the significant inhibition of anti-rat antibody production and deposition in xenografts at Day 6 posttransplant. Furthermore, treatment with anti-HMGB1 antibody suppressed B cell activation and reduced IFN-γ and IL-17A production after xenotransplantation. These results demonstrate for the first time that HMGB1 plays an important role in mediating acute xenograft rejection. Thus, we have shown that neutralization of extracellular HMGB1 can significantly inhibit xenoreactive B cell responses and delay xenograft rejection in a rat-to-mouse model of xenotransplantation, uncovering new insights in the role of HMGB1 in transplantation.

Cleavage pattern predicts developmental potential of day 3 human embryos produced by IVF.

Time-lapse technique provides opportunities to observe the dynamic process of human early development. Previous studies have suggested several abnormal division patterns were associated with decreased developmental potential, but no systematic results are currently available. In this study, seven abnormal division patterns were observed during early cleavage, and these had different effects on the further development potential of daughter blastomeres. According to the severity and occurrence of abnormal division patterns during the initial three cleavages, an embryo hierarchical classification model was developed and day 3 embryos were classified into six grades (from A to F). The good-quality blastocyst formation rate for these grades decreased from 70.8-3.8% (P < 0.001). In a prospective observational study, 139 IVF cycles were recruited to assess the efficiency of this classification model. In the embryos that had confirmed implantation results, the implantation rate decreased from 67.0% (Grade A) to 0% (Grade D;P < 0.001). These results indicated that cleavage patterns can predict the developmental potential of day 3 human embryos.

Impact of early enteral and parenteral nutrition on prealbumin and high-sensitivity C-reactive protein after gastric surgery.

We investigated the impact of early enteral nutrition (EEN) and parenteral nutrition (PN) on prealbumin (PA) and high-sensitivity C-reactive protein (hs-CRP) in patients after gastric cancer surgery. Sixty-eight selected patients undergoing gastric cancer surgery were randomly divided into the EEN (N = 34) and PN (N = 34) groups. Body weight (BW), serum albumin (ALB), transferrin (TF), PA, hs-CRP, length of hospital stay, cost of postoperative nutritional support, and incidence of complications were compared between groups. On postoperative day 7, the BW, TF, ALB, and PA for both groups were significantly decreased compared with the values obtained on preoperative day 1 (P < 0.01). A significant decrease was observed in TF and PA in the PN group compared with the EEN group (P < 0.01). There was no significant difference in BW and ALB between the two groups (P > 0.05). The hs-CRP level of both groups was significantly higher than on preoperative day 1. There was a significant increase in hs-CRP in the PN group compared with the EEN group (P < 0.01). The anal exhaust time, length of hospital stay, and nutritional support cost were significantly shorter or lower in the EEN group than in the PN group (P < 0.01). There was no significant difference in the incidence of complications between the two groups (P > 0.05). EEN helps regulate the postoperative response of patients after gastric cancer surgery, promotes rehabilitation, and accelerates the recovery of gastrointestinal function. Furthermore, EEN has the advantage of being inexpensive.

Impact of early postoperative enteral nutrition on clinical outcomes in patients with gastric cancer.

The impact of early enteral nutrition (EEN) on clinical outcomes of gastric cancer patients was investigated. Three hundred pa-tients undergoing gastric cancer surgery from July 2010 to May 2014 were randomly divided into experimental and control groups (n = 150/group). Experimental group patients received enteral nutrition in water during the early postoperative period. Control group patients received conventional perioperative treatment. Patients' clinical outcomes, post-operative immune function, and nutritional statuses were compared, which revealed that the postoperative fever duration (80.2 ± 6.0 vs 88.1 ± 8.1 h, P < 0.05), anal exhaust time (78.8 ± 9.3 vs 85.3 ± 8.4 h, P < 0.05), and length of hospitalization (7.73 ± 2.13 vs 9.77 ± 1.76 days, P < 0.01) differed significantly. Treatment costs in thousands of dol-lars were 31.24 ± 3.21 for the experimental group and 35.61 ± 2.32 for the control group; this difference was statistically significant (P < 0.01). The incidence of postoperative complications did not significantly differ between the experimental and control groups [14.0% (21/150) vs 17.3% (26/150), P > 0.05]. At postoperative days 3 and 7, the CD3(+), CD4(+), natural killer cell, albumin, and prealbumin levels and CD4(+)/CD8(+) ra-tio were significantly higher in the experimental group than the control group (all P < 0.05). CD8(+) cell counts were significantly lower in the experimental group than the control group (P < 0.05). Postsurgical oral EEN can improve nutritional status and immune function and promote early recovery of intestinal function in patients with gastric cancer.