Effectiveness of a universal resilience-focused intervention for children in the school setting: A randomized controlled trial.

BACKGROUND: Psychological resilience can be augmented through the acquisition of specific cognitive or emotional regulation skills, enabling children to adapt to or recover from stressful events, disadvantages, or adversities. We aimed to evaluate the efficacy of a Tianchang Resilience-focused inTervention program (TRT1 program) on resilience and mental health conditions of Chinese children. METHODS: This study was a two-arm cluster-randomized controlled trial, performed in Tianchang, a county in China. Students from 20 classes in a local primary school (aged 8.7-11.2 years) were randomly allocated to receive a resilience-focused intervention or waitlist group. The intervention comprised weekly 40-min sessions for 14 weeks and co-led by lay counsellors. Measures of emotional symptoms, behavioral difficulties, and resilience were collected at pre-, post-intervention, 6-months, and 12-months follow-up. RESULTS: Between June 16, 2022, and September 4, 2022, 775 eligible students were recruited (mean age 9.93 years; 420 [54.2 %] boys). Relative to the waitlist group (N = 391), the intervention group (N = 384) reported a significant reduction in depressive and anxiety symptoms at post-intervention (all p < 0.001), 6-months (p = 0.007; p = 0.002) and 12-months follow-up (p = 0.018; p = 0.018), respectively. The intervention group effects were also observed on resilience at post-intervention follow-up (p = 0.006), and remained stable over 6-months (p < 0.001) and 12-months follow-up (p = 0.022). CONCLUSIONS: This study demonstrated that the TRT program, a universal resilience-focused intervention for children in the school setting, showed long-term effectiveness in improving resilience and mental health conditions. This minimally trained laypersons-delivered intervention might enhance the program's generalizability to other communities.

Citrate anticoagulation in plasma exchange followed by continuous renal replacement therapy in critically ill children.

OBJECTIVE: To investigate the effectiveness and safety of regional citrate-anticoagulated (RCA) plasma exchange (PE) and whether citrate-related metabolic disorders can be improved by sequential RCA continuous renal replacement therapy (CRRT). METHODS: This retrospective, single-center observational study included 79 critically ill children requiring PE followed by CRRT (June 2018 to June 2021) at the Pediatric Intensive Care Unit of Hunan Children's Hospital, China. Patients were divided into the RCA-PE (n = 30) and systemic heparin anticoagulation (SHA-PE) (n = 49) groups. Filter level comparison post-PE assessed RCA-PE efficacy, and metabolic changes occurring pre- and post-PE and CRRT were used to evaluate the effect of CRRT on RCA-based anticoagulation safety. RESULTS: The RCA-PE group had a better overall filter performance than the SHA-PE group. Two hours after PE, pH and HCO3- levels increased more significantly for the RCA-PE than the SHA-PE group. The RCA-PE incidence of metabolic alkalosis was 48.3%, higher by 4.2% (p < 0.001) compared to the SHA-PE group. In the RCA-PE group, pH and HCO3- decreased significantly 4 h after CRRT; the metabolic alkalosis caused by RCA-PE decreased to 13.8% (p = 0.005). No significant difference in pH, HCO3-, and metabolic alkalosis incidence was observed between the two groups 4 h after CRRT. CONCLUSIONS: The overall filtration performance of RCA-PE is superior to that of SHA-PE followed by CRRT. The metabolic complications associated with RCA-PE are mainly metabolic alkalosis that can be improved by using CRRT after RCA-PE and this is a better alternative for anticoagulation during PE in critically ill children.

Combination therapy of methotrexate and iguratimod for female patients with moderate to severe active rheumatoid arthritis and its impact on ovarian function.

Rheumatoid arthritis is systemic inflammatory disease, presenting as symmetrical polyarthritis, mainly affecting hands and feet. Female patients with rheumatoid arthritis have also decreased fertility and premature ovarian failure. Methotrexate is used in treatment of rheumatoid arthritis. However, single treatment of Methotrexate is not ideal and often needs to be combined with other drugs like Iguratimod for intensive treatment of refractory rheumatoid arthritis. We aim to explore efficacy of combined use of MTX and IGU for female patients with rheumatoid arthritis and its impact on ovarian reserve function. Total 80 female patients with moderate to severe active rheumatoid arthritis were selected and randomly divided into MTX and MTX + IGU groups. The MTX + IGU group showed lower levels of IL-1ß, IL-6, IL-17 and TNF-α after treatment as compared to MTX group. The MTX + IGU group showed significantly higher level of AMH at the end of treatment. However, no statistical differences were observed in FSH, LH, E2 and AFC levels between the two groups. The combined therapy of MTX and IGU has better efficacy with less impact on ovarian function, even improving ovarian reserve function through effective control of rheumatoid inflammatory activity.

Clinical Characteristics of Mild Patients with Breakthrough Infection of Omicron Variant in China after Relaxing the Dynamic Zero COVID-19 Policy.

For SARS-CoV-2 mutants, the effectiveness of the COVID-19 vaccines is still controversial. In this study, we aimed to investigate the clinical characteristics of Omicron-infected patients who completed primary immunization and booster immunization, respectively, during the rapid propagation of the Omicron variant in China. A total of 932 patients with confirmed SARS-CoV-2 infection from 18 December 2022 to 1 January 2023 were included in this survey by filling out questionnaires online. The enrolled patients were divided into the primary immunization group and the booster immunization group according to their vaccination status. During the whole course of disease, the most frequent symptoms were fever (90.6%), cough (84.3%), weakness (77.4%), headache and dizziness (76.1%), and myalgia (73.9%). Nearly 90% of the patients had symptoms lasting for less than 10 days, and 39.8% of the patients ended the course of the disease in 4-6 days. A total of 58.8% of these patients had a fever with a maximum body temperature of over 38.5 °C. Moreover, 61.4% of the patients had a fever that lasted less than 2 days. There were no obvious differences in initial symptoms, cardinal symptoms, symptom duration time, maximum body temperature, and fever duration time between the two groups of patients. In addition, no significant difference was found in the positive or negative conversion time of SARS-CoV-2 antigen/nucleic acid between the two groups of patients. For mild patients with Omicron breakthrough infection, enhanced immunization has no significant impact on the clinical performance and duration of viral infection compared with primary immunization. The reasons behind the different clinical manifestations of patients with mild symptoms after the breakthrough infection of the Omicron strain are still worth further research. Heterologous vaccination may be a better strategy for enhanced immunization, which can help improve the immune protection ability of the population. Further research should be carried out on vaccines against mutant strains and spectral anti-COVID-19 vaccines.

Immunity-related long noncoding RNA WDFY3-AS2 inhibited cell proliferation and metastasis through Wnt/ß-catenin signaling in oral squamous cell carcinoma.

OBJECTIVE: Long noncoding RNA WDFY3-AS2 has been shown to play dual roles in the modulation of cancer progression. This study aimed at clarifying the biological role of WDFY3-AS2 as well as the association between WDFY3-AS2 expression, ß-catenin expression, and OSCC immunity in oral squamous cell carcinoma (OSCC). DESIGN: Bioinformatics analyses, CCK8, EdU, wound healing, transwell, RT-qPCR, western blot, immunofluorescence, in situ hybridization, and immunohistochemistry assays were adopted for exploring the role of WDFY3-AS2 in OSCC. RESULTS: Bioinformatics analyses showed that WDFY3-AS2 conferred a poor prognosis for OSCC patients. Further analyses identified WDFY3-AS2 as an independent prognostic indicator for OSCC. Moreover, silencing WDFY3-AS2 inhibits OSCC cell proliferation, migration and invasion. Gene set enrichment analysis indicated that WDFY3-AS2 participated in the regulation of Wnt signaling. In addition, WDFY3-AS2 expression was positively associated with ß-catenin mRNA levels, the key component of Wnt signaling. Interestingly, WDFY3-AS2 knockdown inhibited ß-catenin expression and nuclear translocation, thus suppressing OSCC progression through Wnt signaling. Furthermore, WDFY3-AS2 expression correlated with an immunosuppressive phenotype in the tumor immune microenvironment. In situ hybridization and immunohistochemistry verified that WDFY3-AS2 was positively associated with total and nuclear ß-catenin protein levels and negatively associated with CD4 expression. CONCLUSIONS: This study demonstrates that the immunity-associated WDFY3-AS2 augments OSCC proliferation and metastasis through Wnt/ß-catenin signaling and may serve as a novel treatment target and a new prognostic factor for OSCC.

Lymphocytes screening on admission is essential for predicting in-hospital clinical outcome in COVID-19 patients: A retrospective cohort study.

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.

Neutrophil-to-lymphocyte ratio, a critical predictor for assessment of disease severity in patients with COVID-19.

INTRODUCTION: Monitoring of laboratory indicators is important for predicting changes in disease severity and clinical outcomes. We aimed to identify the critical predictors that can effectively assess the disease conditions of patients with COVID-19 by analyzing the clinical characteristics and laboratory findings of patients with SARS-CoV-2 infection. METHODS: All consecutive patients (n = 294) with confirmed SARS-CoV-2 infection admitted to the General Hospital of Central Theater Command of the PLA from February 6 to February 21, 2020, were enrolled. These patients were divided into the severe group and the nonsevere group according to disease severity during hospitalization. RESULTS: The median neutrophil-to-lymphocyte ratio (NLR) value of the severe patients was dramatically higher than that of the nonsevere patients (10.4 vs 2.6; P < .001). The NLR value equal to 5 was a boundary value worthy of reference, because more than 80% severe patients had an NLR value greater than 5 and over 80% nonsevere patients had an NLR value less than 5. The NLR value of these COVID-19 patients was positively and respectively correlated with the values of C-reactive protein (R = .5921, P < .001), lactate dehydrogenase (R = .4509, P < .001), procalcitonin (R = .5504, P < .001), fibrinogen (R = .4710, P < .001), and D-dimers (R = .4425, P < .001). However, the NLR value was merely and positively correlated with the interleukin-6 value (R = .3594, P < .05), but had no correlations with the values of interleukin-10, interleukin-4, interleukin-17, interferon-γ, and tumor necrosis factor-α (P > .05). DISCUSSION: Neutrophil-to-lymphocyte ratio is a critical predictor for assessment of disease severity in patients with COVID-19, and it has a close relation with the laboratory indicators related to disease conditions.

Clinical application of Chemiluminescence Microparticle Immunoassay for SARS-CoV-2 infection diagnosis.

BACKGROUND: The unsatisfactory accuracy and capacity of real time RT-PCR depends on several unavoidable reasons, which cannot meet the demands for COVID-19 diagnosis. METHODS: 206 serum samples were collected from patients who were treated in the General Hospital of the Central Theater Command of the PLA between January 18 and April 4, 2020. 270 serum samples from healthy blood donors were used as control. IgM and total antibodies (Ab) against SARS-CoV-2 were detected by Chemiluminescence Microparticle Immunoassay (CMIA). RESULTS: Among the 206 patients, the positive rate of IgM and Ab were 149/206 (72.3 %) and 187/206 (90.8 %), respectively. And the specificity of IgM and Ab detection were 99.3 % and 98.9 %, respectively. The sensitivity of CMIA for Ab detection was significantly higher than that of IgM. An increase of the positive rate and S/CO value for detecting IgM and Ab accompanied with the increasing of days post-disease onset (d.p.o.) were observed. The positive rate of Ab detected by CMIA increased rapidly after 7 d.p.o., while that of IgM was obviously increased after 14 d.p.o.. In addition, the age and gender of these patients did not affect the seroconversion and titer of antibodies during the whole course. The disease-severity of patients had no effect on the seroconversion of antibodies. However, the critical patients possessed a much higher antibody titers than the no-critical cases after 14 d.p.o.. CONCLUSIONS: The CMIA can provide important complementation to nucleic acid assay and help to enhance the accuracy and capacity of diagnosis of SARS-CoV-2 infection.

Evaluation of Nucleocapsid and Spike Protein-Based Enzyme-Linked Immunosorbent Assays for Detecting Antibodies against SARS-CoV-2.

At present, PCR-based nucleic acid detection cannot meet the demands for coronavirus infectious disease (COVID-19) diagnosis. Two hundred fourteen confirmed COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command of the People's Liberation Army between 18 January and 26 February 2020 were recruited. Two enzyme-linked immunosorbent assay (ELISA) kits based on recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, and their diagnostic feasibility was evaluated. Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, respectively. The positive rates of the rN-based and rS-based ELISAs for antibody (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of the rS-based ELISA for IgM detection was significantly higher than that of the rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG ELISAs was less than 60% during the early stage of the illness, 0 to 10 d.p.o., and that of IgM and IgG was obviously increased after 10 d.p.o. ELISA has a high sensitivity, especially for the detection of serum samples from patients after 10 d.p.o., so it could be an important supplementary method for COVID-19 diagnosis.

Glucagon-like peptide-1 inhibits the receptor for advanced glycation endproducts to prevent podocyte apoptosis induced by advanced oxidative protein products.

OBJECTIVE: To investigate whether and how glucagon-like peptide-1 (GLP-1) can protect podocytes from apoptosis induced by advanced oxidative protein products (AOPPs). METHODS: Murine podocytes were stimulated with 200 µg/ml AOPP for 48 h in the presence or absence of GLP-1. Cell viability was assessed using the cell counting kit-8 assay. Podocyte apoptosis was detected by flow cytometry and Hoechst 33258 staining. Superoxide radical production was assayed using lucigenin-enhanced chemiluminescence, and Western blotting was used to measure expression of RAGE, NADPH oxidase subunits p47phox and gp91phox, as well as apoptosis-associated proteins p53, Bax, Bcl-2 and caspase-3. RESULTS: Incubating podocytes with AOPPs reduced cell viability, triggered changes in cell morphology and promoted apoptosis. GLP-1 partially inhibited AOPP-induced apoptosis, O2- overproduction, and AOPP-induced expression of RAGE. GLP-1 inhibited expression of p47phox and gp91phox in AOPP-treated podocytes, and it attenuated AOPP-induced expression of p53, Bax and cleaved caspase-3, whereas it restored expression of Bcl-2. CONCLUSION: GLP-1 partially inhibits AOPP-induced apoptosis in podocytes, perhaps by interfering with the AOPP-RAGE axis, decreasing oxidative stress and inhibiting the downstream p53/Bax/caspase-3 apoptotic pathway. GLP-1 may be a useful anti-apoptotic agent for early intervention in diabetic nephropathy.

[Modified Bianchi orchiopexy for median or low cryptorchidism].

OBJECTIVE: To investigate the effect of modified Bianchi (single incision in the midline of the scrotum) orchiopexy (MBO) versus that of traditional surgery in the treatment of median or low cryptorchidism. METHODS: Eighty-two children with median or low cryptorchidism were treated from February 2013 to February 2014, 46 (53 testes) by MBO and the other 36 by the traditional method of inguinal incision (control, 40 testes). Comparisons were made in the operation time and postoperative complications between the two surgical strategies. RESULTS: The mean operation time was significantly shorter in the MBO group than in the control (ï¼»25±6ï¼½ vs ï¼»35±4ï¼½ min, P<0.05). No testicular atrophy, hernias or hydrocele was found in either group during the 1－2 years of follow-up. Testis retraction was observed in 3 cases in the MBO group as compared with 2 in the control (P>0.05). The incision scar was obvious in all the controls, with 1 case of postoperative inguinal hematoma, but almost invisible in all the MBO cases. CONCLUSIONS: Modified Bianchi orchiopexy is superior to traditional surgery in the treatment of median or low cryptorchidism for its advantages of short operation time, few complications, and satisfactory appearance of the healed incision.

Overexpression of a steroid receptor-binding protein bearing the regulator of the G-protein signaling domain suppresses migration and invasion of human endometrial stromal cells stimulated by 17ß-estradiol.

OBJECTIVE: Endometriosis is an estrogen-dependent disease, a steroid receptor-binding protein bearing the regulator of the G-protein signaling domain (SRB-RGS) can suppress the estrogen receptors-mediated transcriptional activities. We sought to determine whether overexpression of SRB-RGS suppresses the migration and invasion ability of endometrial stromal cells stimulated by 17ß-estradiol (E2). STUDY DESIGN: Endometrial stromal cells were obtained from endometriosis patients. SRB-RGS was overexpressed in the cells stimulated by E2. The migration and invasion ability of the cells were measured by migration assay and invasion assay, respectively. Western blot analysis was done to test the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). RESULTS: Overexpression of SRB-RGS suppressed the migration and invasion ability of the stromal cells stimulated by E2; it also suppressed the expression of MMP-9 and VEGF, while the expression of TIMP-1 was increased. CONCLUSIONS: Overexpression of SRB-RGS suppresses the migration and invasion ability of the E2-stimulated endometrial stromal cells. The molecular mechanism is the reduced expression of MMP-9 and VEGF, and the increased expression of TIMP-1. These findings suggest that the coding gene of SRB-RGS is a promising target gene for endometriosis gene therapy.

[A cross-sectional survey on prevalence and risk factors for abnormal plasma liver enzymes in overweight or obese patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the prevalence and risk factors for abnormal plasma liver enzymes in patients with type 2 diabetes mellitus. METHODS: Overweight or obese patients with type 2 diabetes were recruited from 60 tertiary and secondary hospitals in Guangdong Province between August 2011 and March 2012. The abnormal plasma liver enzymes was diagnosed as alanine aminotransferase >40 U/L and/or aspartate aminotransferase >40 U/L. Binary Logistic regression was used to assess the associations between abnormal plasma liver enzymes and associated risk factors. RESULTS: The abnormal plasma liver enzymes were detected in 709/3543 diabetics with overweight or obesity. And the prevalence of abnormal plasma liver enzymes was 20.0%. According to binary Logistic regression analysis, the presence of abnormal plasma liver enzymes was associated with male gender (OR = 1.603, 95%CI: 1.247-2.061), higher HbA1c(OR = 1.049, 95%CI: 1.005-1.096), higher body mass index (OR = 1.058, 95%CI: 1.014-1.103), higher waist circumference (OR = 1.019, 95%CI: 1.006-1.032), higher triglyceride level (OR = 1.053, 95%CI: 1.008-1.100), adiposis hepatica (OR = 1.543; 95%CI: 1.244-1.914), regular exercises (OR = 0.591, 95%CI: 0.472-0.740) and diet control (OR = 0.794, 95%CI: 0.635-0.993). CONCLUSIONS: There is a high prevalence of abnormal plasma liver enzymes in overweight/obese with diabetics. And decreasing the levels of HbA1c, body mass index, waist circumference and triglycerides, regular exercises and diet control may decrease its prevalence.

[Role of a latent soluble TNF receptor type I (hsTNFRI) fusion protein in targeted treatment of endometriosis].

OBJECTIVE: To construct a latent human soluble tumor necrosis factor receptor I (hsTNFRI) using the latency associated protein (LAP) of transforming growth factor-beta1 (TGF-beta1) fused via a matrix metalloproteinase (MMP) cleavage site to hsTNFRI so as to detect the latent biological activity of LAP-MMP-hsTNFRI fusion protein. METHODS: A double-stranded deoxyoligonucleotide coding for MMP cleavage site was cloned into plasmid pcDNA3.1. LAP and hsTNFRI cDNA were then inserted into both two sides of MMP cleavage site. After being transferred by LAP-MMP-hsTNFRI fusion gene with liposome, the expression of fusion protein in COS-7 cells was detected by RT-PCR and Western blot. The inhibitory effect of fusion protein upon cytotoxicity of TNF-alpha was detected by methyl thiazolyl tetrazolium (MTT) assay before and after the fusion protein incubated in MMP or peritoneal fluid from endometriosis patients. RESULTS: The recombinant plasmid LAP-MMP-hsTNFRI-pcDNA3.1 was constructed successfully and was expressed effectively in COS-7 cells. The MTT assay showed that there was no difference in the mortality rate of L929 cells between LAP-MMP-hsTNFRI-pcDNA3.1 and empty vector transfection groups (P > 0.05). The mortality rates of L929 cells with 800 ng/L TNF-alpha in LAP-MMP-hsTNFRI-pcDNA3.1 transfection group after incubation with MMP or peritoneal fluid from endometriosis patients were (44.5 +/- 2.4)% and (33.8 +/- 1.9)% respectively. And it was lower than the pre-incubation period (58.1 +/- 2.4)% (P < 0.05). CONCLUSION: The biological activity of LAP-MMP-hsTNFRI fusion protein can be made latent by LAP and activated by peritoneal fluid from endometriosis. Thus a new method has been provided for a targeted therapy of endometriosis.

Five new bidesmoside triterpenoid saponins from Stauntonia chinensis.

Eleven triterpenoid saponins (1-11) were isolated from Stauntonia chinensis DC. (Lardizabalaceae), including five new compounds, yemuoside YM(21-25) (1-3, 6, 7) structures of which were elucidated by chemical methods and a combination of MS, 1D- and 2D- NMR experiments including DEPT, (1)H--(1)H COSY, HSQC, HMBC, TOCSY, and NOESY as 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[alpha-L-rhamnopyranosyl-(1 --> 2)-]alpha-L-arabinopyranosyl-akebonicacid-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (1), 3-O-beta-D-xylopyranosyl-(1 --> 3)-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl-akebonic acid-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (2), 3-O-beta-D-glucopyranosyl-(1 --> 3)-alpha-L-arabinopyranosyl-akebonic acid-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (3), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[alpha-L-rhamnopyranosyl-(1 --> 2)-]alpha-L-arabinopyranosyl-akebonic acid-28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (6), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[alpha-L-arabinopyranosyl-(1 --> 2)-]alpha-L-arabinopyranosyl-akebonic acid-28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (7).

Phorbasides A-E, cytotoxic chlorocyclopropane macrolide glycosides from the marine sponge Phorbas sp. CD determination of C-methyl sugar configurations.

Five new cytotoxic macrolide glycosides phorbasides A-E (3-7), each possessing a macrolide ring appended to a rare ene-yne-trans-2-chlorocyclopropane, were isolated from the same Western Australian sponge (Phorbas sp.) that provided phorboxazoles A and B. The structures of 3-7 were solved by analysis of spectroscopic data including NMR, MS, and CD. A synthesis of methyl 2-O-methyl-alpha-L-evalose from L-rhamnose was completed and used for configurational assignment of the sugar residue in 3. Acid-catalyzed methanolysis of 3 followed by two-step derivatization of the liberated O-methyl glycoside gave a vicinal 4-O-naphthoyl/tertiary 3-N-(2-aminonaphthyl)carbamate derivative that exhibited exciton coupled CD identical with that of the derivative prepared from synthetic 1,2- O-dimethyl-alpha-L-evalose.

[The experimental study of biomimetic artificial cartilage fabrication in vitro and ectopic chondrogenesis in vivo].

Tri-dimensional poly (DL-lactic-co-glycolic acid) (PLGA) scaffolds were fabricated using a rapid prototyping (RP) technique and the gene of human bone morphogenetic protein 2 (hBMP-2) was transferred into rabbit bone marrow stromal cells (MSCs) via recombinant adeno-associated virus vectors (rAAV-hBMP-2). Thirty-two PLGA scaffolds, size (4 mm X 4 mm X 4 mm), were coated with collagen type I and equally divided into 2 groups. In group A, each scaffold was loaded with 2 X 10(4) hBMP-2 (+) MSCs to establish a hBMP-2 (+) MSCs/PLGA composite. In group B, each scaffold was loaded with 2 X 10(4) hBMP-2 (-) MSCs to establish a hBMP-2 (-) MSCs/PLGA composite. The composites in both groups were cultured for subcutaneous implantation in nude mice. All animals were killed 30 days after implantation and the differentiation of composites was evaluated. As a result, MSCs infected with rAAV-hBMP-2 efficiently expressed hBMP-2 protein. RP-based PLGA scaffolds had ideal microarchitecture. The diameters of macropore and micropore of the scaffolds were 300 microm and 3-5 microm, respectively. At 3-5 days after culture, a number of seeding cells well grew on the scaffolds of both groups. The composites in group A had chondrogenesis ability in vivo and the expression of collagen type II was positive. In group B, however, only polymers and fiber tissues were predominantly found. The percentage of polymer remnant area was significantly lower in group A than in group B (P<0.01). Our results therefore indicate that RP-based PLGA scaffolds efficiently coated with collagen type I have good biocompatibility with hBMP-2 (+) MSCs and the techniques developed in this study may favor cartilage tissue engineering.

Effects of Smac gene over-expression on the radiotherapeutic sensitivities of cervical cancer cell line HeLa.

BACKGROUND: The second mitochondria-derived activator of caspases (Smac) is a novel proapoptotic gene, which plays an important role in the apoptosis-inducing effects of irradiation on tumor cells. The purpose of this study was to investigate the effects of extrinsic Smac gene transfer and its over-expression in radiotherapeutic sensitivities of cervical cancer cells. METHODS: After the Smac gene was transferred into the cervical cancer cell line HeLa, subcloned cells were obtained by persistent G418 selection. Cellular Smac gene expression was detected by RT-PCR and Western blot, while in vitro cell viabilities were detected by trypan blue staining assay. After treatment with X-ray irradiation, cellular radiotherapeutic sensitivities were investigated by tetrazolium bromide colorimetry. Cellular apoptosis and its rate were determined by electronic microscopy, annexin V-FITC and propidium iodide staining flow cytometry. The expression and activities of cellular caspase-3 were assayed by Western blot and colorimetry. RESULTS: Smac mRNA and protein levels in HeLa/Smac cells and the selected subclone cell line of cervical cancer were significantly higher than those of HeLa (P < 0.01). There was no significant difference in cellular viabilities between them (P > 0.05). However, after irradiation with 8 Gy X-ray, growth activities of HeLa/Smac were reduced by 22.42% (P < 0.01). When compared with those of HeLa, partial HeLa/Smac cells presented characteristic morphological changes of apoptosis under electronic microscope, with higher apoptosis rates (16.4% vs. 6.2%, P < 0.01); the caspase-3 expression levels in HeLa/Smac cells were improved significantly (P < 0.01), while its activities were increased by 3.42 times (P < 0.01). CONCLUSIONS: Stable transfer of the extrinsic Smac gene and its over-expression in cervical cancer cell line could significantly enhance the expression and activities of cellular caspase-3 and ameliorate apoptosis-inducing effects of irradiation on cancer cells, which was a novel strategy to improve radiotherapeutic effects on cervical cancer.

[Effect of retroperitoneal lymphadenectomy on survival of patients with epithelial ovarian cancer].

OBJECTIVE: The purpose of this study was to determine prognostic factors that have an impact on overall survival and to assess the rational application of retroperitoneal lymphadenectomy in patients with epithelial ovarian cancer. METHODS: A retrospective review was performed of 131 patients treated between Jan.1990 and Dec.1998 in Union Hospital and Tongji Hospital. Survival was calculated by Kaplan-Meier method and comparison was performed using Log-rank test. Independent prognostic factors were identified by the COX proportional hazards regression model. RESULTS: Multivariate analysis showed that the age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy were the most important prognostic factors. The overall 5-year survival was 66% and 41% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). But the survival rate could not be improved through retroperitoneal lymphadenectomy in the patients with early stage, advanced stage whose residual tumor > 2 cm and those with mucinous adenocarcinoma (P > 0.05). Among patients with advanced stage whose residual tumor < or = 2 cm, 5-year survival was 65% and 30% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). Among patients with serous adenocarcinoma, 5-year survival was 61% and 31% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). CONCLUSIONS: The prognosis of the patients with epithelial ovarian cancer may be influenced by age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy. Although retroperitoneal lymphadenectomy could improve the survival rate, it should be carried out selectively.