Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Research progress of anti-tumor in situ gel delivery system / 药学学报

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.

Serum Sclerostin and Its Association with Bone Turnover Marker in Metabolic Bone Diseases.

Sclerostin is a secreted inhibitor of Wnt/ß-catenin signaling that is mainly produced by osteocytes and is an important regulator of bone remodeling. Some studies have evaluated serum sclerostin levels in metabolic bone diseases, but the results have been contradictory. The profile of serum sclerostin levels in patients with osteogenesis imperfecta (OI), X-linked hypophosphatemia (XLH), and Paget's disease of bone (PDB) was obtained to determine their association with bone turnover marker. Serum sclerostin levels, biochemical parameters, and the bone turnover marker, ß-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (ß-CTX), were measured in 278 individuals, comprising 71 patients with OI, 51 patients with XLH, 17 patients with PDB, and 139 age- and sex-matched healthy controls. A correlation analysis was performed between sclerostin and ß-CTX concentration. The univariate logistic regression analysis was used to analyze factors associated with OI, XLH, and PDB. Patients with PDB (11 male 6 female), aged 44.47 ± 14.75 years; XLH (17 male, 34 female), aged 19.29 ± 15.65 years; and OI (43 male, 28 female), aged 19.57 ± 16.45 years, had higher sclerostin level than age- and sex-matched healthy controls [median(interquartile range): 291.60 (153.42, 357.35) vs. 38.00 (27.06, 68.52) pmol/L, 163.40 (125.10, 238.20) vs. 31.13 (20.37, 45.84) pmol/L, and 130.50 (96.12, 160.80) vs. 119.00 (98.89, 194.80) pmol/L, respectively; P < 0.001]. Patients with PDB had the highest level of serum sclerostin, followed by those with XLH and OI (P < 0.05). Sclerostin was positively correlated with ß-CTX in OI and XLH (r = 0.541 and r = 0.661, respectively; P < 0.001). Higher ß-CTX and sclerostin levels were associated with a higher risk of OI, XLH, and PBD. Sclerostin may be a biomarker of OI, XLH, and PDB. Whether sclerostin inhibitors can be used in these patients requires further analysis using additional cohorts.

MouseVenue3D: A Markerless Three-Dimension Behavioral Tracking System for Matching Two-Photon Brain Imaging in Free-Moving Mice.

Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional (3-D) space. However, there is no available three-dimensional behavior capture system that focuses on rodents. Here, we present MouseVenue3D, an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents. We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module. Then, we validated this process in behavior recognition tasks, and showed that 3-D behavioral data achieved higher accuracy than 2-D data. Subsequently, MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse. Finally, we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice. Our findings reveal that subtle, spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.

Adenovirus vector encoding TPPII ignites HBV-specific CTL response by activating autophagy in CD8+ T cell.

Early studies have shown that autophagy and TPPII are associated with HBV infection. In this study, adenovirus vector containing TPPII was constructed to immunize HBV transgenic mice in vivo to explore the potential mechanism of autophagy and HBV infection. Our goal is to provide new ideas for immunotherapy of hepatitis B. First, adenovirus vector containing TPPII was constructed. Then, we used adenovirus to immunize HBV transgenic mice and ATG5 knockout HBV transgenic mice. The autophagy of CD8+ T cells was detected by transmission electron microscopy and immunofluorescence electron microscopy, Western blot was used to detect the expression of autophagy LC3 and BECN1, CTL reaction, HBV DNA and HBsAg in serum, HBsAg and HBcAg in liver tissues by immunohistochemistry, to further examine the possible mechanisms involved in autophagy. Adv-HBcAg-TPPII promotes autophagy of CD8+ T lymphocyte, activates CTL response, inhibits HBV DNA replication and HBsAg expression, and PI3K/ Akt /m TOR signalling pathway may be involved in autophagy. This study demonstrates that autophagy of CD8+ T cells was induced by Adv-HBcAg-TPPII and the molecular mechanism may be related to the PI3K/ Akt /m TOR signalling pathway, providing a possible theoretical basis for immunotherapy of hepatitis B.

MouseVenue3D: A Markerless Three-Dimension Behavioral Tracking System for Matching Two-Photon Brain Imaging in Free-Moving Mice / 神经科学通报·英文版

Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional (3-D) space. However, there is no available three-dimensional behavior capture system that focuses on rodents. Here, we present MouseVenue3D, an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents. We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module. Then, we validated this process in behavior recognition tasks, and showed that 3-D behavioral data achieved higher accuracy than 2-D data. Subsequently, MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse. Finally, we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice. Our findings reveal that subtle, spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.

A novel mutation of AMHR2 in two brothers with persistent Müllerian duct syndrome and their intracytoplasmic sperm injection outcome.

BACKGROUND: Persistent Müllerian duct syndrome (PMDS) is defined as the presence of Müllerian duct derivatives in an otherwise normally virilized 46, XY male. It is usually caused by homozygous or compound heterozygous mutations in either the anti-Müllerian hormone (AMH) or AMH receptor type 2 (AMHR2) genes. The main purpose of the study is to determine the novel mutations of AMHR2 in PMDS patients and their intracytoplasmic sperm injection outcomes (ICSI). METHODS: Whole-exome sequencing (WES) was carried out. Sanger sequencing was used to detect mutations in AMHR2. The pathogenicity of the identified variant and its possible effects on the protein were evaluated with in silico tools. The expression level of AMHR2 was determined by Western blotting. The spermatogenic function was evaluated by testicular sperm aspiration and histopathologic examination. The ICSI outcomes were recorded. RESULTS: We present two brothers with a history of bilateral cryptorchidism with orchidopexy and infertility due to azoospermia. A novel compound heterozygous mutation of c.1219C>T [p.R407X] and c.1387C>T [p.R463C] in exons 9 and 10 of AMHR2 (NM_020547.2) was detected by whole-exome sequencing (WES). Spermatozoon could be retrieved from the two patients by testicular aspiration following intracytoplasmic sperm injection (ICSI) due to azoospermia. Finally, patient 1 had two healthy boys and patient 2 failed to conceive after three ICSI attempts. CONCLUSION: The spermatozoa could obtain from PMDS patients due to azoospermia. For patients with bilateral cryptorchidism, PMDS should be included in the differential diagnosis and that genetic counseling needs to be considered when they seek reproductive help.

Effect of resveratrol on mouse ovarian vitrification and transplantation.

BACKGROUND: After ovarian tissue transplantation, ischemia-reperfusion injury and free radicals cause follicle depletion and apoptosis. Therefore, the use of antioxidants to reduce the production of free radicals is an important method to address the consequences of ischemia-reperfusion injury. Resveratrol is a natural active polyphenol compound with anti-inflammatory, antitumor, strong antioxidant and anti-free radical properties. The aim of this study was to investigate whether resveratrol could improve the effect of autologous ovarian transplantation after cryopreserve-thawn mouse ovarian tissue. METHODS: Whole-ovary vitrification and autotransplantation models were used to investigate the effects of resveratrol. Six-week-old female mice from the Institute of Cancer Research (ICR) were subjected to vitrification. All ovaries were preserved in liquid nitrogen for 1 week before being thawed. After thawing, ovarian tissues were autotransplanted in the bilateral kidney capsules. Mice (n = 72) were randomly divided into four groups to determine the optimal concentration of resveratrol (experiment I). Treatments were given as follows: saline, 5 mg/kg resveratrol, 15 mg/kg resveratrol and 45 mg/kg resveratrol, which were administered orally for one week. Grafted ovaries were collected for analysis on days 3, 7, and 21 after transplantation. Ovarian follicle morphology was assessed by hematoxylin and eosin staining. Serum FSH and E2 levels were measured to estimate the transplanted ovarian reserve and endocrine function. Other mice were randomly divided into two groups-saline and 45 mg/kg resveratrol to further evaluate the effect of resveratrol and explore the mechanisms underlying this effect (experiment II). Ovarian follicle apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays. Immunohistochemistry, qRT-PCR and western blotting (MDA, SOD, NF-κB, IL-6 and SIRT1) were used to explore the mechanisms of resveratrol. Moreover, oocytes derived from autotransplanted ovaries at 21 days were cultured and fertilized in vitro. RESULTS: The proportions of morphologically normal (G1) follicles at 3, 7 and 21 days were significantly higher in the 45 mg/kg resveratrol group than in the saline group. The TUNEL-stained follicles (%) at 7 days were significantly decreased in the 45 mg/kg resveratrol group compared with the saline group. Western blot analysis revealed that SOD2 and SIRT1 levels were significantly higher in the 45 mg/kg resveratrol group than in the saline group at day 7 and that MDA and NF-κB levels were lower in the saline group on day 3. Likewise, IL-6 was lower in the saline group on day 7. These results are basically consistent with the qRT-PCR results. In addition, the mean number of retrieved oocytes and fertilization and cleavage were significantly increased in the 45 mg/kg resveratrol group compared with the saline group. CONCLUSIONS: Administration of resveratrol could improve the quality of cryopreserved mouse ovarian tissue after transplantation and the embryo outcome, through anti-inflammatory and antioxidative mechanisms.

Factors Correlating to the Development of Hepatitis C Virus Infection among Drug Users-Findings from a Systematic Review and Meta-Analysis.

Hepatitis C remains a significant public health threat. However, the main routes of transmission have changed since the early 1990s. Currently, drug use is the main source of hepatitis C virus (HCV) infection, and some measures have been successively implemented and additional studies have been published. However, the factors correlating with HCV infection failed to clearly define. Our study pooled the odds ratios (ORs) with 95% confidence intervals (CIs) and analyzed sensitivity by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Publication bias was determined by Egger's test. In our meta-analysis, HCV-infected and non-HCV-infected patients from 49 studies were analyzed. The pooled ORs with 95% CIs for study factors were as follows: Injecting drug use 10.11 (8.54, 11.97); sharing needles and syringes 2.24 (1.78, 2.83); duration of drug use >5 years 2.39 (1.54, 3.71); unemployment 1.50 (1.22, 1.85); commercial sexual behavior 1.00 (0.73, 1.38); married or cohabiting with a regular partner 0.88 (0.79, 0.98), and sexual behavior without a condom 1.72 (1.07, 2.78). This study found that drug users with histories of injecting drug use, sharing needles and syringes, drug use duration of >5 years, and unemployment, were at increased risk of HCV infection. Our findings indicate that sterile needles and syringes should be made available to ensure safe injection. In view of that, methadone maintenance treatment can reduce or put an end to risky drug-use behaviors, and should be scaled up further, thereby reducing HCV infection.

Advances in research on exosomes as drug delivery vehicles / 药学学报

Exosomes are membranous vesicles that are actively secreted by cells. They can be isolated from various cell culture media and animal body fluids. Exosomes are mainly composed of lipids, proteins and nucleic acids. They have small molecular structure and high biocompatibility with size of 40-100 nm. In addition, exosomes are natural endogenous nanocarriers that can transport lipids, proteins, DNA and RNA. Studies have shown that exosomes play an important role in long-distance communication between cells, in physiological and pathological processes. This article introduces the composition and physiological functions of exosomes, and summarizes the relevant content of exosomes as drug delivery vehicles. The applications of exosomes in central nervous system diseases, especially brain diseases and tumors are summarized.

Recent advances in the drug formulations of anti-tumor antibiotics / 药学学报

Anti-tumor antibiotics exhibit great application potential in the anti-tumor therapy. Some drugs have become the first-line medication clinically. However, there are always various problems associated with anti-tumor antibiotics, such as poor solubility and instability as well as severe systemic side effects. It is important to choose suitable delivery carriers for a reasonable delivery system for a good targeting ability, enhanced anti-tumor efficacy and reduced adverse effects of the anti-tumor antibiotics, especially in the smart delivery systems. This review summarizes the carriers and the advances in the delivery systems of anti-tumor antibiotics, including anti-tumor antibiotic drugs currently on the market, in the clinical research stage and in the basic research stage.

Prognostic Impact of Cell Division Cycle Associated 2 Expression on Pancreatic Ductal Adenocarcinoma / 中国医学科学杂志(英文版)

<strong>Objective</strong> To examine the expression of cell division cycle associated 2 (CDCA 2) in pancreatic ductal adenocarcinoma (PDAC) and investigate its role in prognosis of PDAC patients. <strong>Methods</strong> This retrospective study included 155 PDAC patients who underwent surgical treatment and complete post-operative follow-up. Clinicopathologic data were collected through clinical database. Tissue microarray was constructed and immunohistochemistry was performed to detect CDCA2 expression in the PDAC tumor tissues and adjacent non-tumor tissues. Clinicopathological characteristics between high and low CDCA2 expression were compared. Correlation of CDCA2 expressions with patients' survival was analyzed using Kaplan-Meier method and Cox regression analysis. <strong>Results</strong> Expression of CDCA2 in PDAC cells was significantly higher than that in adjacent non-tumor tissues (U=4056.5, P<0.001). Univariate analysis showed that CDCA2 expression [hazard ratio (HR)=1.574, 95% confidence interval (CI)=1.014-2.443, P=0.043] and node metastasis (HR=1.704, 95%CI=1.183-2.454, P=0.004) were significantly associated with prognosis. Cox regression analysis showed CDCA2 expression was not an independent prognostic risk factor (HR=1.418, 95%CI=0.897-2.242, P=0.135) for PDCA patients. Stratification survival analysis demonstrated CDCA2 expression as an independent prognostic risk factor in male patients (HR=2.554, 95%CI=1.446-4.511, P=0.003) or in non-perineural invasion patients (HR=2.290, 95%CI=1.146-4.577, P=0.012). <strong>Conclusions</strong> CDCA2 is highly expressed in PDAC tumor tissue. Although CDCA2 is not an independent prognostic risk factor for PDAC patients, it might be used to help predict prognosis of male or non-perineural invasion patients of PDAC.

Prognostic Impact of Cell Division Cycle Associated 2 Expression on Pancreatic Ductal Adenocarcinoma / 中国医学科学杂志(英文版)

Objective To examine the expression of cell division cycle associated 2 (CDCA 2) in pancreatic ductal adenocarcinoma (PDAC) and investigate its role in prognosis of PDAC patients. Methods This retrospective study included 155 PDAC patients who underwent surgical treatment and complete post-operative follow-up. Clinicopathologic data were collected through clinical database. Tissue microarray was constructed and immunohistochemistry was performed to detect CDCA2 expression in the PDAC tumor tissues and adjacent non-tumor tissues. Clinicopathological characteristics between high and low CDCA2 expression were compared. Correlation of CDCA2 expressions with patients' survival was analyzed using Kaplan-Meier method and Cox regression analysis. Results Expression of CDCA2 in PDAC cells was significantly higher than that in adjacent non-tumor tissues (U=4056.5, P<0.001). Univariate analysis showed that CDCA2 expression [hazard ratio (HR)=1.574, 95% confidence interval (CI)=1.014-2.443, P=0.043] and node metastasis (HR=1.704, 95%CI=1.183-2.454, P=0.004) were significantly associated with prognosis. Cox regression analysis showed CDCA2 expression was not an independent prognostic risk factor (HR=1.418, 95%CI=0.897-2.242, P=0.135) for PDCA patients. Stratification survival analysis demonstrated CDCA2 expression as an independent prognostic risk factor in male patients (HR=2.554, 95%CI=1.446-4.511, P=0.003) or in non-perineural invasion patients (HR=2.290, 95%CI=1.146-4.577, P=0.012). Conclusions CDCA2 is highly expressed in PDAC tumor tissue. Although CDCA2 is not an independent prognostic risk factor for PDAC patients, it might be used to help predict prognosis of male or non-perineural invasion patients of PDAC.

The development of cell-penetrating peptides in drug delivery system / 药学学报

Cell membrane serves as the natural barrier. Cell-penetrating peptides (CPPs) have been a powerful vehicle for the intracellular delivery of a large variety of cargoes cross the cell membrane. The efficiency of intracellular delivery of drugs, proteins, peptides and nucleic acid, as well as various nanoparticu-late pharmaceutical carriers (e.g., liposomes, polymeric micelles and inorganic nanoparticles) has been demon-strated both in vitro and in vivo. This review focuses on the CPPs-based strategy for intracellular delivery of small molecule drugs, proteins, peptides, nucleic acid and CPP-modified nanocarriers.

Hepatitis B virus-associated glomerulonephritis in HBsAg serological-negative patients.

OBJECTIVE: The main objective of this study is to report the clinical and pathological characteristics of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) in serum hepatitis B surface antigen (HBsAg)-negative patients in China. HBV-GN is caused by the HBV's attack on the kidney tissues, but definitive diagnostic criteria are still lacking. The diagnostic criteria used in China require HBsAg positivity in the serum, but research on occult HBV infection has shown that HBV infection is also found in serum HBsAg-negative patients. Clinical and pathological characterization of HBV-GN in serum HBsAg-negative patients is required. MATERIALS AND METHODS: Serologic and clinical findings and pathological characteristics of renal tissues in 18 HBV-GN patients (11 men and seven women) with serum HBsAg negativity were analyzed retrospectively. Thirty-three HBV-GN patients with serum HBsAg positivity and 59 patients with membranous nephropathy (MN) without any HBV infection markers in serum and renal tissues during the same period were included as controls. RESULTS: Among the 18 HBsAg-negative patients with GN, 12 had HBsAb positivity in their sera. None of the patients was positive for serum HBeAg. Proteinuria was the major clinical manifestation and the renal histopathology was characterized as MN. Immune fluorescence deposits in renal tissues consisted mainly of HBsAg. The degree of renal injury and the decrease in the C3 level were less than those in HBsAg-positive patients and idiopathic membranous nephropathy patients. CONCLUSION: We propose to use the HBV marker in renal tissues as a new diagnostic criterion for HBV-GN. If MN patients have HBV marker positivity in renal tissues, HBV-GN can be diagnosed even without HBsAg in the serum. This would improve the diagnostic accuracy and potential treatment efficiency.

Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles / 华中科技大学学报（医学）（英德文版）

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles / 华中科技大学学报（医学）（英德文版）

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring.

AIM: Genetic variation in ALOX12, which encoded human 12-lipoxygenase, was found to be associated with fat mass in young Chinese men. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese nuclear families with male offspring. METHODS: We recruited 1,296 subjects from 427 nuclear families with male offspring and genotyped five SNPs (rs9894225, rs748694, rs2619112, rs2619118, and rs916055) in the ALOX15 gene locus. The total fat mass (TFM), trunk fat mass (tFM), leg fat mass (LFM) and arm fat mass (AFM) were measured using dual-energy X-ray absorptiometry (DXA). The percentage of fat mass (PFM) was the ratio of TFM and body weight. The association between SNPs and haplotypes of ALOX15 and obesity-related phenotypic variation was measured using quantitative transmission disequilibrium test (QTDT). RESULTS: Using QTDT to measure family-based genetic association, we found that rs916055 had a statistically significant association with PFM (P=0.038), whereas rs916055 had a marginal but statistically insignificant association with tFM (P=0.093). The multiple-parameter 1000 permutations test agreed with the family-based association results: both showed that rs916055 had a statistically significant association with PFM (P=0.033). CONCLUSION: rs916055 in ALOX15 gene was significantly associated with the percentage of fat mass in Chinese nuclear families with male offspring in the family-based association study using QTDT approach.

A new effective method in the treatment of severe ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a recognized complication of ovulation induction, occurring in 1-10% of IVF and embryo transfer cycles. While mild OHSS is of no clinical relevance, severe OHSS is a life threatening complication. However, the efficacy of prevalent treatments appeared to be limited. We developed a continuous autotransfusion system with an ultrafiltration instrument for reinfusion the protein of concentrated ascites for the treatment of severe OHSS. OBJECTIVE: To study the efficacy and safety of using a continuous autotransfusion system for the treatment of severe OHSS. MATERIALS AND METHODS: 69 patients with severe OHSS who were treated with controlled ovarian hyperstimulation due to infertility from February 2002 to August 2010 in our reproductive center were divided into two groups. One group treated with continuous autotransfusion system with an ultrafiltration instrument which infused the protein of concentrated ascites, called ultrafiltration group, another group were treated with simple-albumin supplement, called albumin group. Several examinational results and adverse effect were compared between the two groups. RESULTS: The volume of urine output after 72h in ultrafiltration group was more than that in albumin group, the waist circumference and body weight in ultrafiltration group were lower than those in albumin group after 72h. The serum creatinine levels after 72h in ultrafiltration group was still significantly lower than that in albumin group (p<0.05). The ultrafiltration group rarely showed adverse effect compared with albumin group. CONCLUSION: Autotransfusion of protein in concentrated ascites for the treatment of severe ovarian hyperstimulation syndrome was effective and safe.

Association between low density lipoprotein receptor-related protein 2 gene polymorphisms and bone mineral density variation in Chinese population.

Low density lipoprotein receptor-related protein 2 gene (LRP2) is located next to the genomic region showing suggestive linkage with both hip and wrist bone mineral density (BMD) phenotypes. LRP2 knockout mice showed severe vitamin D deficiency and bone disease, indicating the involvement of LRP2 in the preservation of vitamin D metabolites and delivery of the precursor to the kidney for the generation of 1α,25(OH)(2)D(3). In order to investigate the contribution of LRP2 gene polymorphisms to the variation of BMD in Chinese population, a total of 330 Chinese female-offspring nuclear families with 1088 individuals and 400 Chinese male-offspring nuclear families with 1215 individuals were genotyped at six tagSNPs of the LRP2 gene (rs2389557, rs2544381, rs7600336, rs10210408, rs2075252 and rs4667591). BMD values at the lumbar spine 1-4 (L1-4) and hip sites were measured by DXA. The association between LRP2 polymorphisms and BMD phenotypes was assessed by quantitative transmission disequilibrium tests (QTDTs) in female- and male-offspring nuclear families separately. In the female-offspring nuclear families, rs2075252 and haplotype GA of rs4667591 and rs2075252 were identified in the nominally significant total association with peak BMD at L1-4; however, no significant within-family association was found between peak BMD at the L1-4 and hip sites and six tagSNPs or haplotypes. In male-offspring nuclear families, neither the six tagSNPs nor the haplotypes was in total association or within-family association with the peak BMD variation at the L1-4 and hip sites by QTDT analysis. Our findings suggested that the polymorphisms of LRP2 gene is not a major factor that contributes to the peak BMD variation in Chinese population.