Clinical application and pharmacokinetic study of nanocarriers in drug delivery system / 药学学报

Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.

Platelet membrane-camouflaged silver metal-organic framework drug system against infections caused by methicillin-resistant Staphylococcus aureus.

BACKGROUND: Due to the intelligent survival strategy and self-preservation of methicillin-resistant Staphylococcus aureus (MRSA), many antibiotics are ineffective in treating MRSA infections. Nano-drug delivery systems have emerged as a new method to overcome this barrier. The aim of this study was to construct a novel nano-drug delivery system for the treatment of MRSA infection, and to evaluate the therapeutic effect and biotoxicity of this system. We prepared a nano silver metal-organic framework using 2-methylimidazole as ligand and silver nitrate as ion provider. Vancomycin (Vanc) was loaded with Ag-MOF, and nano-sized platelet vesicles were prepared to encapsulate Ag-MOF-Vanc, thus forming the novel platelet membrane-camouflaged nanoparticles PLT@Ag-MOF-Vanc. RESULTS: The synthesized Ag-MOF particles had uniform size and shape of radiating corona. The mean nanoparticle size and zeta potential of PLT@Ag-MOF-Vanc were 148 nm and - 25.6 mV, respectively. The encapsulation efficiency (EE) and loading efficiency (LE) of vancomycin were 81.0 and 64.7 %, respectively. PLT@Ag-MOF-Vanc was shown to be a pH-responsive nano-drug delivery system with good biocompatibility. Ag-MOF had a good inhibitory effect on the growth of three common clinical strains (Escherichia coli, Pseudomonas aeruginosa, and S. aureus). PLT@Ag-MOF-Vanc showed better antibacterial activity against common clinical strains in vitro than free vancomycin. PLT@Ag-MOF-Vanc killed MRSA through multiple approaches, including interfering with the metabolism of bacteria, catalyzing reactive oxygen species production, destroying the integrity of cell membrane, and inhibiting biofilm formation. Due to the encapsulation of the platelet membrane, PLT@Ag-MOF-Vanc can bind to the surface of the MRSA bacteria and the sites of MRSA infection. PLT@Ag-MOF-Vanc had a good anti-infective effect in mouse MRSA pneumonia model, which was significantly superior to free vancomycin, and has no obvious toxicity. CONCLUSIONS: PLT@Ag-MOF-Vanc is a novel effective targeted drug delivery system, which is expected to be used safely in anti-infective therapy of MRSA.

[Effect of electroacupuncture on expression of p-ERK1/2 and c-fos in spinal dorsal horn in rats with interstitial cystitis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) and "Huiyang" (BL35) on the expression of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and cellular oncogene fos (c-fos) phosphorylated of spinal dorsal horn in rats with interstitial cystitis (IC). METHODS: Eighteen female Wistar rats were randomly divided into control, model and EA groups, with 6 rats in each group. The IC model was established by intraperitoneal injection of cyclophosphamide (150 mg/kg). EA (30 Hz, 1 mA) was applied to bilateral BL32 and BL35 for 20 min, once daily for 3 consecutive days. The bladder pain was measured by using a Von Frey at 48 h after modeling and 24 h after EA. The expression levels of p-ERK1/2 and c-fos protein in L6-S1 segment of spinal cord were detected by Western blot, and the expression of p-ERK1/2 and c-fos in the right spinal dorsal horn were displayed by immunofluorescence staining. RESULTS: After modeling, the bladder mechanical pain threshold (PT) was significantly decreased (P<0.05), the protein expression of p-ERK1/2 and c-fos in the spinal cord was increased (P<0.05) and the immunofluorescence surface density of p-ERK1/2 and c-fos in the right dorsal horn of spinal cord was increased (P<0.05) in the model group relevant to the control group. After EA intervention, IC-induced reduction of PT, and increases of the expression of p-ERK1/2 and c-fos as well as immunofluorescence surface density of p-ERK1/2 and c-fos were reversed in the EA group relevant to the model group (P<0.05). CONCLUSION: EA at BL 32 and BL 35 has an analgesic effect in IC rats, which may be related to its effect in down-regulating the expression of p-ERK1/2 and c-fos in spinal dorsal horn.

The necessity of treating asymptomatic bacteriuria with antibiotics in the perioperative period of joint arthroplasty: a metaanalysis

Background/aim: Oral antibiotics are usually used to treat asymptomatic bacteriuria during the perioperative period of joint replacement. However, there is no unified conclusion as to whether asymptomatic bacteriuria causes infection around joint prostheses, and the efficacy of antibiotics is unknown. Materials and methods: We systematically searched PubMed, CNKI, Ovid, Cochrane Library, EMBASE, manual research, and references of relevant articles up to January 1, 2020, to identify and compare observational studies. The Cochrane systematic review method was used, and Review Manager 5.3 software was used for analysis. Results: Nine articles were included in the analysis, involving 29,844 cases of joint arthroplasty and 2366 cases of asymptomatic bacteriuria. Periprosthetic joint infection had a significantly higher incidence in the asymptomatic bacteriuria group than in the nonasymptomatic bacteriuria group (Odds Ratio: OR = 3.15, 95% CI: 1.23­8.02, P = 0.02). Seven of the nine articles reported the use of antibiotics for treating perioperative asymptomatic bacteriuria and there was no significant difference in the incidence of periprosthetic joint infection between the two groups (OR = 1.64, 95% CI: 0.84­3.23, P = 0.15). Conclusion: The occurrence of asymptomatic bacteriuria in the perioperative period of joint arthroplasty is a risk factor for periprosthetic joint infection, and the use of antibiotics for asymptomatic bacteriuria does not change the rate of incidence.

[Effect of electroacupuncture at different acupoints on follicle development and related factors in serum and ovary tissues of PCOS rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at different acupoints on follicle development, expression of gonadotropins and their receptors and anti-Müllerian hormone(AMH), inhibin B(INHB) in polycystic ovarian syndrome (PCOS) rats, so as to explore its mechanisms underlying improvement of PCOS. METHODS: Sixty female SD rats were randomized into six groups: control, model, Zusanli(ST36), Sanyinjiao(SP6), Guanyuan(CV4) and combination (ST36+SP6+CV4, n=10 rats/group). The PCOS model was established by gavage of Letrozole solution (1.0 mg/kg) once daily for 21 consecutive days. Rats of the control group were given 1% Carboxymethyl Cellulose (CMC, 1 mg/kg). EA (2 Hz) was applied to ST36, SP6, or/and CV4 for 20 min, once daily for 14 consecutive days. The number of follicles was counted, and the ovarian structure and follicular development were observed under light microscope after H.E. stain, and the contents of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), AMH, and INHB were assayed by enzyme-linked immunosorbent assay, and the ratio of LH/FSH was calcula-ted. The immunoactivity of LH receptor (LHR) and FSH receptor (FSHR) proteins was detected by immunohistochemistry. RESULTS: After modeling, the number of follicles at the growth stage, contents of serum LH, AMH and INHB, and ratio of LH/FSH were significantly increased, and serum FSH level and FSHR, LHR immunoactivity were remarkably decreased in the model group relevant to the control group (P<0.05, P<0.01). Following EA intervention, the number of follicles at the growth stage in the SP6, CV4 and combination groups, LH/FSH ratio and serum AMH levels in the 4 EA groups, INHB contents in the ST36, CV4 and combination groups were significantly reduced (P<0.05, P<0.01), while serum FSH contents in the 4 EA groups, FSHR immunoactivity at the early stage in the ST36 group and LHR immunoactivity at both early and late stages in the ST36 and CV4 groups were considerably increased in comparison with those of the model group (P<0.01, P<0.05). The therapeutic effect of SP6 was significantly superior to that of CV4 in down-regulating serum LH level (P<0.01), but significantly inferior to that of CV4 in up-regulating serum FSH content and in down-regulating LH/FSH ratio and serum AMH and INHB levels (P<0.05, P<0.01). The effect of CV4 was comparable to that of ST36 in up-regulating serum FSH, and in down-regulating serum LH/FSH ratio, AMH and INHB levels (P>0.05). CONCLUSION: EA of CV4, SP6, ST36 and ST36+CV4+SP6 can reduce the number of follicles at the growth stage and regulate the expression levels of gonadotropins in PCOS rats. The effects of EA of CV4 and ST36 are evidently better than those of EA of SP6 in up-regulating serum FSH content and in down-regulating LH/FSH ratio, and serum AMH and INHB levels, and EA of SP6 is evidently superior to EA of CV4 down-regulating LH level, but without synergistic effect among the 3 acupoints.

Defective [Bi2 O2 ]2+ Layers Exhibiting Ultrabroad Near-Infrared Luminescence.

Aurivillius phases have been routinely known as excellent ferroelectrics and have rarely been deemed as materials that luminesce in the near-infrared (NIR) region. Herein, it is shown that the Aurivillius phases can demonstrate broadband NIR luminescence that covers telecommunication and biological optical windows. Experimental characterization of the model system Bi2.14 Sr0.75 Ta2 O9-x , combined with theoretical calculations, help to establish that the NIR luminescence originates from defective [Bi2 O2 ]2+ layers. Importantly, the generality of this finding is validated based on observations of a rich bank of NIR luminescence characteristics in other Aurivillius phases. This work highlights that incorporating defects into infinitely repeating [Bi2 O2 ]2+ layers can be used as a powerful tool to space-selectively impart unusual luminescence emitters to Aurivillius-phase ferroelectrics, which not only offers an optical probe for the examination of defect states in ferroelectrics, but also provides possibilities for coupling of the ferroelectric property with NIR luminescence.

Unconventional CN vacancies suppress iron-leaching in Prussian blue analogue pre-catalyst for boosted oxygen evolution catalysis.

The incorporation of defects, such as vacancies, into functional materials could substantially tailor their intrinsic properties. Progress in vacancy chemistry has enabled advances in many technological applications, but creating new type of vacancies in existing material system remains a big challenge. We show here that ionized nitrogen plasma can break bonds of iron-carbon-nitrogen-nickel units in nickel-iron Prussian blue analogues, forming unconventional carbon-nitrogen vacancies. We study oxygen evolution reaction on the carbon-nitrogen vacancy-mediated Prussian blue analogues, which exhibit a low overpotential of 283 millivolts at 10 milliamperes per square centimeter in alkali, far exceeding that of original Prussian blue analogues and previously reported oxygen evolution catalysts with vacancies. We ascribe this enhancement to the in-situ generated nickel-iron oxy(hydroxide) active layer during oxygen evolution reaction, where the Fe leaching was significantly suppressed by the unconventional carbon-nitrogen vacancies. This work opens up opportunities for producing vacancy defects in nanomaterials for broad applications.

[Effect of Electroacupuncture at Different Acupoints on Steroid Hormones and Ovarian Androgen Receptor Expression in Polycystic Ovary Syndrome Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at different acupoints on hyperandrogenism and ovarian androgen receptor (AR) expression in rats with polycystic ovary syndrome (PCOS), so as to explore its mechanisms underlying improvement of PCOS. METHODS: Sixty female SD rats were randomly divided into control, model, Zusanli (ST 36), Sanyinjiao (SP 6), Guanyuan (CV 4) and comprehensive groups (10 rats/group). The PCOS model was established by giving (gavage) the animals with Letrozole solution (1.0 mg/kg), once daily for 21 consecutive days. EA stimulation was applied to ST 36, SP 6, or CV 4 respectively, once daily for 14 days. The comprehensive group was treated by EA treatment of the abovementioned three acupoints in the meantime. Before and after the treatment, the body mass and the ovary weight were measured. The morphological structure of the ovary was observed under microscope after H．E. staining. The levels of serum hormone and sex hormone binding globulin (SHBG) were assayed by ELISA. Free androgen index (FAI) was calculated and the expression of AR in the ovary was detected by immunohistochemistry. RESULTS: After modeling, the body mass, ovary weight, serum testosterone (T) and FAI levels and the expression of AR protein in late ovarian follicles were significantly increased (P<0.01, P<0.05), and serum estradiol (E2) and SHBG contents were significantly decreased relevant to the control group (P<0.01). Following EA intervention and compared with the model group, the body weight of each EA group was significantly reduced (P<0.05), the ovarian pathological changes were improved, and serum T and FAI levels were significantly decreased (P<0.01), and serum E2 and SHBG contents significantly increased in the ST 36, CV 4 and comprehensive groups (P<0.01, P<0.05). The ovary weight of only CV 4 group was significantly lower than that of the model group (P<0.01). The expression of AR protein in late follicles of both CV 4 and SP 6 groups was markedly decreased (P<0.05, P<0.01). CONCLUSION: EA at ST 36, SP 6, and CV 4 all can improve the hyperandrogenism and ovarian polycystic morphological changes of PCOS rats, while different acupoints have different functional characteristics.

Primary issues in the selection of surgical procedures for thoracic and lumbar spinal tuberculosis.

Debridement, spinal canal decompression, deformity correction, bone graft fusion and internal fixation are commonly used in the surgical treatment of spinal tuberculosis. A complete surgical plan for patients with spinal tuberculosis may include all or some of these five surgical procedures that involve both removing tuberculous lesions and re-establishing spinal stability and function. All five procedures can be carried out via an anterior or posterior approach or a combination of these two approaches. A combined posterior-anterior approach is becoming a preferred choice for treating spinal tuberculosis. However, this procedure requires two incisions and two rounds of surgeries, which the associated extensive surgical trauma. Thus, a simple anterior or posterior approach may be preferable. Each of these approaches has its own advantages and disadvantages that must be considered during the clinician's evaluation. Selection of the most appropriate of these three approaches is vital to achieving cure of spinal tuberculosis. Spinal surgeons should comprehensively consider each patient's characteristics, the manifestations of their lesions and how familiar the surgeon is with the required surgical procedure(s). The primary consideration should be the potential outcome: the effectiveness of debridement is the key determinant of the surgical outcome.

Correlation of tumor necrosis factor-ß and interleukin-1 gene cluster polymorphism with susceptibility to bacteremia in patients undergoing kidney transplantation.

BACKGROUND: Bacteremia remains a significant cause of morbidity and mortality after kidney transplantation. This study was conducted to investigate whether the polymorphisms of tumor necrosis factor (TNF)-ß, interleukin (IL)-1ß, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to bacteremia within the first 6 months after kidney transplantation. METHODS: Subjects comprised 82 infected kidney transplant recipients and 60 non-infected kidney transplant recipients. Bacteremia was diagnosed in 16 of the 82 infected recipients. Genomic DNA from these 142 kidney transplant recipients was extracted from peripheral blood leukocytes. Regions containing the NcoI polymorphic site at position +252 of TNF-ß gene and the AvaI polymorphic site at position -511 of IL-1ß gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI and AvaI restriction enzymes, respectively. The polymorphic regions within intron 2 of IL-1ra gene containing variable numbers of a tandem repeat (VNTR) of 86 base pairs were amplified by PCR. RESULTS: Genotypic and allelic frequencies were similar between infected recipients and non-infected ones. Individual locus analysis showed that recipient TNF-ß and IL-1ra gene polymorphisms were not associated with the presence of bacteremia (P = 0.684 and P = 0.567, respectively). However, genotype analysis revealed that recipient IL-1ß-511CC genotype was strongly associated with susceptibility to develop bacteremia (P = 0.003). Recipient IL-1ß-511CC genotype (odds ratio 5.242, 95% confidence intervals 1.645-16.706, P = 0.005) independently predicted the risk for bacteremia within the first 6 months after kidney transplantation. CONCLUSIONS: These findings indicate a critical role of IL-1ß gene polymorphisms in susceptibility to bacteremia after kidney transplantation, which may be useful to screen for patients at higher risk for post-transplant bacteremias. Thus, the identified individuals can benefit from preventive treatment and a less potent immunosuppressive regimen.

Correlation of tumor necrosis factor-β and interleukin-1 gene cluster polymorphism with susceptibility to bacteremia in patients undergoing kidney transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacteremia remains a significant cause of morbidity and mortality after kidney transplantation. This study was conducted to investigate whether the polymorphisms of tumor necrosis factor (TNF)-β, interleukin (IL)-1β, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to bacteremia within the first 6 months after kidney transplantation.</p><p><b>METHODS</b>Subjects comprised 82 infected kidney transplant recipients and 60 non-infected kidney transplant recipients. Bacteremia was diagnosed in 16 of the 82 infected recipients. Genomic DNA from these 142 kidney transplant recipients was extracted from peripheral blood leukocytes. Regions containing the NcoI polymorphic site at position +252 of TNF-β gene and the AvaI polymorphic site at position -511 of IL-1β gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI and AvaI restriction enzymes, respectively. The polymorphic regions within intron 2 of IL-1ra gene containing variable numbers of a tandem repeat (VNTR) of 86 base pairs were amplified by PCR.</p><p><b>RESULTS</b>Genotypic and allelic frequencies were similar between infected recipients and non-infected ones. Individual locus analysis showed that recipient TNF-β and IL-1ra gene polymorphisms were not associated with the presence of bacteremia (P = 0.684 and P = 0.567, respectively). However, genotype analysis revealed that recipient IL-1β-511CC genotype was strongly associated with susceptibility to develop bacteremia (P = 0.003). Recipient IL-1β-511CC genotype (odds ratio 5.242, 95% confidence intervals 1.645-16.706, P = 0.005) independently predicted the risk for bacteremia within the first 6 months after kidney transplantation.</p><p><b>CONCLUSIONS</b>These findings indicate a critical role of IL-1β gene polymorphisms in susceptibility to bacteremia after kidney transplantation, which may be useful to screen for patients at higher risk for post-transplant bacteremias. Thus, the identified individuals can benefit from preventive treatment and a less potent immunosuppressive regimen.</p>

[Pattern of lymph node metastasis and extent of lymphadenectomy for distal gastric cancer].

OBJECTIVE: To analyze lymph node (LN) metastasis patterns and determine the appropriate extent of LN dissection in distal-third gastric cancer. METHODS: Clinical data of 545 patients with distal third gastric cancer undergoing radical operation in the Fujian Provincial Hospital between 2001 and 2010 were analyzed retrospectively. The metastasis rate for each LN station was analyzed stratified by the depth of tumor invasion. RESULTS: The incidence of LN metastasis in this cohort was 38.2% (208/545). LN metastasis rate in mucosal cancer was 2.0% (2/99) and involved LNs were limited to station 1 LN stations. LN metastasis rate in submucosal cancer was 18.9% (18/95), significantly higher than that in mucosal cancer (P<0.01). The metastasis rates to groups No.7, 8 and 9 in station 2 were 5.3% (5/94), 3.2% (3/94), and 1.1% (1/89) respectively. In addition, 3 cases (3.2%) had metastasis in station 2 outside the range of groups 7, 8 and 9 including groups No.1, 11p and 12. Gastric cancer invading the muscularis propria or deeper layers showed an significant increased rate of metastasis (P<0.01). CONCLUSION: D1 dissection seems to be sufficient for mucosal cancer. Standard D2 dissection should be performed for cancers of the muscularis propria or deeper. For submucosal cancer, an extended D1+ dissection is required for complete removal of metastatic nodes.

Intervertebral focal surgery for the treatment of non-contiguous multifocal spinal tuberculosis.

PURPOSE: The purpose of this study was to assess the clinical efficacy of intervertebral focal surgery by complete debridement, deformity correction, graft fusion, and internal fixation for patients with non-contiguous multifocal spinal tuberculosis. METHODS: A total of 29 cases with non-contiguous multifocal spinal tuberculosis admitted to the hospital from January 2000 to January 2007 were treated by intervertebral focal surgery. There were 63 foci in 29 cases, averaging 2.2 foci per case, and 146 affected vertebral bodies, averaging 2.3 vertebral bodies per focus. Three cases had one normal intervertebral disc between two foci, and the other 26 cases had two or more normal intervertebral discs between two foci. RESULTS: All cases were followed-up for an average of five years. The kyphosis showed a mean correction rate of 67.7% after surgery. A mean loss rate of correction of 8.2% was observed at the final follow-up. The levels of erythrocyte sedimentation rate and C-reactive protein returned to normal in 27 cases on average at 5.8 months and bone union could be observed at five months after surgery. Eleven cases with nerve damage recovered to E grade at the final follow-up. CONCLUSIONS: Intervertebral focal surgery by complete debridement, deformity correction, graft fusion, and internal fixation for patients with non-contiguous multifocal spinal tuberculosis was feasible and effective.

Pattern of lymph node metastasis and extent of lymphadenectomy for distal gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze lymph node (LN) metastasis patterns and determine the appropriate extent of LN dissection in distal-third gastric cancer.</p><p><b>METHODS</b>Clinical data of 545 patients with distal third gastric cancer undergoing radical operation in the Fujian Provincial Hospital between 2001 and 2010 were analyzed retrospectively. The metastasis rate for each LN station was analyzed stratified by the depth of tumor invasion.</p><p><b>RESULTS</b>The incidence of LN metastasis in this cohort was 38.2% (208/545). LN metastasis rate in mucosal cancer was 2.0% (2/99) and involved LNs were limited to station 1 LN stations. LN metastasis rate in submucosal cancer was 18.9% (18/95), significantly higher than that in mucosal cancer (P<0.01). The metastasis rates to groups No.7, 8 and 9 in station 2 were 5.3% (5/94), 3.2% (3/94), and 1.1% (1/89) respectively. In addition, 3 cases (3.2%) had metastasis in station 2 outside the range of groups 7, 8 and 9 including groups No.1, 11p and 12. Gastric cancer invading the muscularis propria or deeper layers showed an significant increased rate of metastasis (P<0.01).</p><p><b>CONCLUSION</b>D1 dissection seems to be sufficient for mucosal cancer. Standard D2 dissection should be performed for cancers of the muscularis propria or deeper. For submucosal cancer, an extended D1+ dissection is required for complete removal of metastatic nodes.</p>

[Analysis of prognostic factors in lymph node-negative advanced gastric cancer patients].

OBJECTIVE: To investigate the prognostic factors of lymph node-negative advanced gastric cancer patients in order to guide adjunctive therapy and surveillance tragedy. METHODS: A total of 236 advanced gastric cancer patients with no less than 12 retrieved lymph nodes and without lymph node metastasis from Fujian Provincial Hospital between 1998 and 2008 were collected retrospectively. Univariate and multivariate prognostic analysis were performed. RESULTS: Two hundred and twenty-four patients(94.9%) were followed up and 5-year overall and disease-free survival rates were 75.2% and 66.4% respectively. Univariate prognostic analysis showed that depth of infiltration, Lauren histotype and retrieved lymph nodes were associated with 5-year overall survival(all P<0.05). Multivariate prognostic analysis testified that depth of infiltration was independent prognostic predictor(P<0.05). Recurrent rates of T2 and T3 patients were 5.8%(8/138) and 14.0%(12/86),5-year overall survival rates were 82.5% and 59.0%, 5-year disease-free survival rates were 70.4% and 52.2% respectively. These differences were all statistically significant (all P<0.05). CONCLUSIONS: T2N0 gastric cancer patients have a better prognosis than T3N0 patients. Depth of infiltration should be considered to stratify lymph node-negative gastric cancer patients for an adjunctive treatment and follow-up scheduling.

Analysis of prognostic factors in lymph node-negative advanced gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors of lymph node-negative advanced gastric cancer patients in order to guide adjunctive therapy and surveillance tragedy.</p><p><b>METHODS</b>A total of 236 advanced gastric cancer patients with no less than 12 retrieved lymph nodes and without lymph node metastasis from Fujian Provincial Hospital between 1998 and 2008 were collected retrospectively. Univariate and multivariate prognostic analysis were performed.</p><p><b>RESULTS</b>Two hundred and twenty-four patients(94.9%) were followed up and 5-year overall and disease-free survival rates were 75.2% and 66.4% respectively. Univariate prognostic analysis showed that depth of infiltration, Lauren histotype and retrieved lymph nodes were associated with 5-year overall survival(all P<0.05). Multivariate prognostic analysis testified that depth of infiltration was independent prognostic predictor(P<0.05). Recurrent rates of T2 and T3 patients were 5.8%(8/138) and 14.0%(12/86),5-year overall survival rates were 82.5% and 59.0%, 5-year disease-free survival rates were 70.4% and 52.2% respectively. These differences were all statistically significant (all P<0.05).</p><p><b>CONCLUSIONS</b>T2N0 gastric cancer patients have a better prognosis than T3N0 patients. Depth of infiltration should be considered to stratify lymph node-negative gastric cancer patients for an adjunctive treatment and follow-up scheduling.</p>

Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia.

Estrogen has important roles in the initiation and development of benign prostatic hyperplasia (BPH). Regulators of the estrogen receptor (ER) are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene (Ral), on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines: a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry (IHC) for proliferating cell nuclear antigen and alpha-smooth muscle actin. In vitro and in vivo, tamoxifen (Tam), another anti-estrogen drug, and finasteride (Fin), a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthermore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin (P < 0.05). Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators.

[Analysis of antibiotics treatment in 86 cases of liver transplant recipients].

OBJECTIVE: To analyze the characteristic of bacterial infections, and the relationship between antibiotics treatment and bacterial infections after liver transplantation, and to prevent antibiotic-resistant bacterial infections. METHODS: 86 liver transplant recipients were retrospected. Different indexes including limited daily dose, the frequency of medication, drug use index were used to evaluate the rationality of the use of antibiotics, three-dimensional test was used to explore extended-spectrum beta-lactamase and AmpC enzyme of Gram-negative bacteria. RESULTS: The major pathogens of infection after liver transplantation were Enterococcus faecalis, Enterobacter cloacae, fungi and E. coli. Pre-operative antibiotic utilization rate was 83.7%, it was mainly a single use of antibiotics; After- operative antibiotic usage was 100.0%, it was mainly joint use of two or three antibiotics; The top 3 antibiotics used were cephalosporins, the combined enzyme inhibitors and penicillin. Antibiotics with drug utilization index (DUI) more than 1.1 included ampicillin and Lalin proxy. 43.3% and 31.8% of Gram -Negative bacteria produced ESBLs and AmpC, respectively, while 21.3% Gram -Negative bacteria produced two enzymes. CONCLUSION: There is high incidence of bacterial infections after liver transplantation. The use of antibiotics is high dose, high-frequency and reasonable; High resistance of bacterial infections was prone to develop and the prevention of the high resistance of bacterial infections is very important.

Proliferation and phenotypic changes of stromal cells in response to varying estrogen/androgen levels in castrated rats.

It is known that human benign prostatic hyperplasia might arise from an estrogen/androgen (E/T) imbalance. We studied the response of castrated rat prostate to different ratios of circulating E/T. The castrated male Wistar rats were randomly injected with E/T at different ratios for 4 weeks. The prostates of E/T (1:100) group showed a distinct prostatic hyperplasia response by prostatic index, hematoxylin and eosin staining, and quantitative immunohistochemical analysis of alpha-smooth muscle actin (SMA). In this group, cells positive for Vimentin, non-muscle myosin heavy chain (NMMHC) and proliferating cell nuclear antigen (PCNA) increased in the stroma and epithelium. Furthermore, the mRNA levels of smooth muscle myosin heavy chain (SMMHC) and NMMHC increased. So E/T at a ratio of 1:100 can induce a stromal hyperplastic response in the prostate of castrated rats. The main change observed was an increase of smooth muscle cells, whereas some epithelial changes were also seen in the rat prostates.