In order to explore the effect and underlying mechanism of hypoxia on body weight, the effect of intermittent moderate hypoxia on high-fat diet-induced obesity was observed in mice, and the role of leptin in hypoxic effect was identified. Healthy Kunming mice were divided randomly into 4 groups (n=20 in each group). The control group: the mice were fed normally under the normal oxygen pressure. Hypoxia group: the mice were fed normally, and given intermittent moderate hypoxia training. Obesity group: the mice were fed diet rich in fat and sugar under the normal oxygen pressure. Hypoxia + obesity group: the mice were fed diet rich in fat and sugar, and given intermittent moderate hypoxia training. After 40 d of feeding and training, the body weight of mice was determined, and the average increasing rate of body weight in each group was calculated and normalized with food intake. Meanwhile, plasma leptin level was measured with ELISA method, and fatty degeneration and leptin receptor expression in liver were observed by Sudan III staining and immunohistochemistry, respectively. The obesity mouse model was successfully established with increases in body weight, plasma leptin level and distribution of adipocytes in the liver. The average body weight and density of adipocytes in the liver in hypoxia and hypoxia + obesity groups decreased obviously, while plasma leptin level and leptin receptor expression in the liver were increased. It is suggested that intermittent moderate hypoxia reduces body weight through elevating plasma leptin level and/or enhancing leptin receptor expression in the liver.
Adipocytes ; cytology ; Animals ; Body Weight ; Female ; Hypoxia ; metabolism ; pathology ; Immunohistochemistry ; Leptin ; blood ; Liver ; chemistry ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; Receptors, Leptin ; analysis

OBJECTIVETo evaluate the association between white blood cell count and the risk of cardiovascular diseases (CVD) in subjects aged 35 - 64 years.

METHODSThis prospective study was carried out in 11 provinces from 1992 to 2003. The association of baseline white blood cell count and cardiovascular disease occurrence was analyzed in 30 384 subjects aged 35 - 64 years using Cox multivariate proportional hazards regression.

RESULTS(1) Compared with the group of 4.0 - 4.9 x 10(9)/L, multivariate-adjusted relative risk of ischemic cardiovascular disease (ICVD, including coronary heart disease and ischemic stroke) increased continuously in proportion to increased white blood cell count. (2) White blood cell count had different impact on different types of CVD. Positive association was observed between white blood cell count and the risk of ischemic stroke, but the relationship between white blood cell count and the risk of hemorrhagic stroke was not significant. Compared with the referent group (4.0 - 4.9 x 10(9)/L), the risk of coronary heart disease of the group of white blood count > 9.0 x 10(9)/L increased by 70% (RR = 1.71, P < 0.05) and that of ischemic stroke increased by 80% (RR = 1.85, P < 0.01).

CONCLUSIONThe risk of ICVD and CVD increases continuously in proportion to increased white blood cell count, the white blood cell count might be used to predict future risk of CVD, especially risk for ICVD.

Adult ; Asian Continental Ancestry Group ; Cardiovascular Diseases ; epidemiology ; China ; epidemiology ; Female ; Humans ; Leukocyte Count ; statistics & numerical data ; Male ; Middle Aged ; Prospective Studies ; Risk Assessment ; Risk Factors

OBJECTIVETo analyze phenotype and genotype of three Chinese pedigrees with von Willebrand disease (vWD), and explore the molecular mechanism.

METHODSBleeding time (BT), activated partial thromboplastin time (APTT), ristocetin-induced platelet aggregation (RIPA), von Willebrand factor (vWF): ristocetin cofactor (RCof) (vWF:RCof), vWF antigen (vWF:Ag), vWF activity (vWF:A) test, vWF collagen binding assay (vWF:CB), vWF and Factor VIII (FVIII) binding assay (vWF:FVIII:B) and multimer analysis were used for phenotype diagnosis. Genomic DNA was extracted from the peripheral blood (PB). All the 52 exons and flanking sequences of the probands' vWF gene were amplified by PCR and analyzed by direct sequencing.

RESULTSAPTT were prolonged in all three probands, while BT were normal excepting for proband 3. Plasma RIPA, vWF:RCo, vWF:Ag, vWF:A and vWF:CB were decreased in different extents. In multimer analysis, proband 3 lost the large and intermediate molecular weight multimers, while proband 1 and 2 were normal. Gene analysis in the three probands revealed three heterozygous missense mutations of 144067 G→A (R2287Q) in exon 39, 110374G→A (R1374H) and 110770C→T (S1506L) in exon 28 and heterozygous polymorphism 110667G→A (D1472H) in exon 28, respectively.

CONCLUSIONThe three heterozygous mutations (R2287Q, R1374H and S1506L) and an heterozygous polymorphism (D1472H) are genetic defects of the hereditary vWD of the three pedigrees respectively. R2287Q is a novel mutation reported for the first time in the literature.

Adult ; Child ; DNA Mutational Analysis ; Female ; Genotype ; Heterozygote ; Humans ; Male ; Pedigree ; Phenotype ; von Willebrand Diseases ; diagnosis ; genetics ; von Willebrand Factor ; genetics ; metabolism

Objective: To investigate the antibacterial properties, biocompatibility and mechanical properties of Cu-ZnO-loaded dental veneering porcelain to provide an experimental basis for the development of new dental veneering porcelain. Methods: Cu-ZnO nanoparticles were added to IPS E.max Ceram for restorative veneer porcelain at different mass percentages of 0 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, and 6 wt% using ball milling in ceramic powder. A cylindrical specimen with a diameter of 20 mm and a thickness of 2 mm was prepared by high-temperature sintering. Scanning electron microscopy was used to observe the surface morphologies of nano-Cu-ZnO and the specimens. The antibacterial effect of Escherichia coli (E. coli) was quantitatively studied by the plate colony counting method. The CCK-8 method was used to evaluate in vitro the cytotoxicity of the tested piece to mouse fibroblasts (L929). Live and dead cells were observed by fluorescence microscopy. The mechanical properties of modified IPS E. Max Ceram veneering porcelain were tested by a three-point bending strength test. Results : Under the scanning electron microscope, Cu-ZnO appears with a block-like structure and can be seen dispersed in the veneering porcelain. When the nano Cu-ZnO loading was 1 wt%, 2 wt%, 3 wt%, and 4 wt%, the antibacterial rates of the specimens were 24.85%, 67.94%, 96.92%, and 99.99%, respectively, and the difference between the experimental groups and the control group was statistically significant (F = 23.308,P = 0.001). The relative growth rate of each group was greater than 80% after coculture with mouse fibroblast cells (L929) for 1 day and 3 days, and there was no significant difference between the groups. The morphology of L929 cells was normal after coculture for 24 hours. With the increase in the Cu-ZnO concentration, the flexural strength of the specimen exhibited an increasing trend followed by a decreasing trend. The bending strength of the specimen loaded with 3 wt% nano Cu-ZnO reached the maximum value (84.728 ± 6.82) MPa, and there was no statistically significant difference between groups (F = 0.633,P = 0.702). Conclusion The antibacterial rate of IPS E. max Ceram veneering porcelain loaded with 3 wt% nano Cu-ZnO was more than 96% against E. coli after high-temperature sintering at 750 ℃. The bending strength reached the maximum (84.728 ± 6.82) MPa, and there was no obvious cytotoxicity.

OBJECTIVETo evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer.

METHODSFrom December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered.

RESULTSThe overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%).

CONCLUSIONCapecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.

Adult ; Aged ; Antimetabolites, Antineoplastic ; therapeutic use ; Capecitabine ; Colorectal Neoplasms ; drug therapy ; mortality ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; Humans ; Male ; Middle Aged ; Survival Rate

To explore the optimal therapy time for the treatment of severe coronavirus disease 2019(COVID-19)by traditional Chinese medicine(TCM)and its influence on the therapeutic effect and prognosis. The clinical data,laboratory findings,and outcomes of 64 patients with severe COVID-19 treated with TCM and western medicine in Chongqing from January 20,2020, to March 11,2020 were retrospectively analyzed.Patients were divided into early intervention group[TCM was initiated within 3 days (including day 3) after the first diagnosis of severe type/critical type COVID-19]and late intervention group[TCM was initiated after 7 days (including day 7) after the first diagnosis of severe type /critical type COVID-19].The changes in clinical parameters during the course of disease were compared between the two groups. On day 14,the oxygenation index was 292.5(252.0,351.0)mmHg in the early intervention group,which was significantly higher than that in the late intervention group [246.0(170.0,292.5)mmHg](=0.005).The length of hospital stay [(18.56±1.11)d (24.87±1.64)d,=0.001],duration of ICU stay [(14.12±0.91)d (20.00±1.53)d,=0.000] and time to negativity [(16.77±1.04)d (22.48±1.66)d,=0.001] in the early intervention group were significantly shorter than those in the late intervention group.The intubation rate(7.3%)in the early intervention group was significantly lower than that in the late intervention group(30.4%)(=0.028). Early TCM therapy within three days after a diagnosis of severe COVID-19 can shorten the length of hospital stay,duration of ICU stay,and time to negativity and decrease intubation rate.
Betacoronavirus ; Coronavirus Infections ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prognosis ; Retrospective Studies

OBJECTIVE: To verrify the anti-tumor efficacy and toxicity between juglone (Jug) and Jug-loaded PLGA nanoparticles (Jug-PLGA-NPs). METHODS: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug (2, 3, 4 µg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 µg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. RESULTS: With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo (P<0.05 or P<0.01) with acceptable biocompatibility. CONCLUSIONS Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.
Animals ; Cell Line, Tumor ; Delayed-Action Preparations/therapeutic use* ; Drug Carriers/therapeutic use* ; Melanoma/pathology* ; Mice ; Mice, Nude ; Nanoparticles ; Naphthoquinones ; Particle Size ; Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER NCT03620565, https://register.clinicaltrials.gov.
China ; Female ; Gynecologic Surgical Procedures/adverse effects* ; Humans ; Pelvic Floor/surgery* ; Pelvic Organ Prolapse/surgery* ; Surgical Mesh/adverse effects* ; Treatment Outcome ; Vagina