[Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China].

Objective: To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. Methods: The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. Results: The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M (Q1, Q3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) µg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95%CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion: Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

[Study on formulation and revision of standard limit for formaldehyde in the "Standards for indoor air quality（GB/T 18883-2022）" in China].

Formaldehyde, as an important pollutant in indoor air, has always been of great concern. In the newly issued "Standards for indoor air quality (GB/T 18883-2022)", the standard limit of formaldehyde has been restricted to 0.08 mg/m3. In order to better promote the implementation and application of this new standard, this study reviewed and interpreted the relevant technical content for determining the standard limit, including the indoor concentration and human exposure levels of formaldehyde, the health effects of formaldehyde, and the derivation of safety reference values. It also proposed prospect for the future development and revision of quality standards for formaldehyde in indoor air.

[Interpretation of the World Society of Emergency Surgery Guidelines for Diagnosis and Treatment of Acute Left Colonic Diverticulitis in the Elderly (2022 edition)].

Acute colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. Acute left colonic diverticulitis in the elderly presents with unique epidemiological features when compared with younger patients. Elderly patients have a lower risk of recurrent episodes, higher in-hospital and postoperative mortality. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) formulated the guidelines for diagnosis and treatment of acute left colonic diverticulitis in the elderly (2022 edition). This article aims to interpret the guidelines statements on the following topics: diagnosis, management, non-surgical therapy and surgical technique.

Neuropilin1, a novel independent prognostic factor and therapeutic target in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer, and thus, has limited treatment options. Neuropilin1 (NRP1) is a multi-functional transmembrane protein that interacts with a number of signaling receptors and plays an important role in cancer progression. Previous studies demonstrated that the expression of NRP1 is activated and promotes the progression of breast cancer particularly in TNBC compared to other molecular subtypes; however, whether or not the level of NRP1 expression is related to the progression of TNBC warrants further study. In the current study, we determined the expression and function of NRP1 and evaluated the clinical significance of NRP1 in patients with TNBC. In addition, we determined whether or not an NRP1 antagonist potentiates the inhibitory effects of paclitaxel (PTX) in patients with TNBC. In our clinical study, NRP1 had higher expression in TNBC tissues than non-TNBC tissues at the same stage, and NRP1 was an independent prognostic factor. Specifically, the high expression of NRP1 was associated with shorter survival in TNBC patients. In addition, TNBC cells treated with NRP1 antagonist significantly potentiated the effect of PTX on cell proliferation, cell migration, and apoptosis. Our findings suggest that NRP1 expression can act as an independent prognostic factor for TNBC patients, and the combination of PTX and an NRP1 antagonist may be an effective treatment regimen for TNBC.

Expressions of VEGF and miR-21 in tumor tissues of cervical cancer patients with HPV infection and their relationships with prognosis.

OBJECTIVE: To investigate the expressions of vascular endothelial growth factor (VEGF) and micro-ribonucleic acid-21 (miR-21) in cervical cancer patients with human papillomavirus (HPV) infection and determine the potential relationships with prognosis. PATIENTS AND METHODS: Expressions of VEGF in cervical cancer tissues and cancer-adjacent tissues were detected by immunohistochemistry, and the expressions of miR-21 and VEGF in both tissues were quantitatively analyzed using reverse transcription polymerase chain reaction (RT-PCR). Patients with cervical cancer were followed up after operation, and the survival rates of patients with different expression levels of miR-21 and VEGF were compared. RESULTS: VEGF was expressed in both cervical cancer tissues and cancer-adjacent tissues. The positive expression rate of VEGF in cervical cancer tissues (75.69%) was significantly higher than that in cancer-adjacent tissues (10.45%). RT-PCR results showed that the expression levels of miR-21 and VEGF in cervical cancer tissues were significantly higher than those in cancer-adjacent tissues (p<0.05). Correlation analyses revealed that miR-21 expression was significantly positively correlated with VEGF expression in cervical cancer tissues (r2=0.4174, p<0.0001). Prognostic analyses showed that the 5-year survival rate of patients was relatively high when miR-21 and VEGF were lowly expressed. CONCLUSIONS: VEGF and miR-21 are highly expressed in tumor tissues of cervical cancer patients with HPV infection. VEGF expression is significantly positively correlated with miR-21 expression, and the high levels of VEGF and miR-21 predict unfavorable prognosis of cervical cancer. Data provide a theoretical support for clinical treatment of cervical cancer patients with HPV infection.

[Correlation between serum uric acid level and acute renal injury after coronary artery bypass grafting].

Objective: To evaluate whether early postoperative serum uric acid level can predict postoperative acute renal injury (AKI) among patients undergoing coronary artery bypass grafting (CABG). Methods: The study retrospectively enrolled 1 306 patients undergoing CABG in Fuwai Hospital between September 2012 and December 2013. The patients were divided into 5 groups by the concentrations of serum uric acid measured on the morning of the first postoperative day, and uric acid categories were as follow: less than 195 µmol/L (Q1 group, 262 cases), 195-236 µmol/L (Q2 group, 263 cases), 237-280 µmol/L (Q3 group, 260 cases), 281-336 µmol/L (Q4 group, 261 cases), more than 336 µmol/L (Q5 group, 260 cases). The primary end points were AKI (RIFLE criteria), severe AKI (AKI≥stage Ⅰ), postoperative continuous renal replacement therapy (CRRT) requirement, in-hospital death, length of stay in hospital and intensive care unit(ICU). The area under the receiver-operating characteristic (ROC) curve (AUC) was used to determine the ability of the early postoperative serum uric acid level as a risk factor for postoperative AKI prediction. Results: Among the 1 306 patients enrolled in the study, AKI was found in 335 patients (25.65%). After adjusting for variables that were different between the 5 groups, the Q5 group had significantly higher risk of AKI, AKI≥ stage Ⅰ and the requirement of CRRT (P<0.01). The ROC for the outcome of postoperative AKI had an AUC of 0.648 (95% CI: 0.612-0.683) when serum creatinine levels alone were used and 0.722 (95% CI: 0.688-0.755) when serum uric acid levels alone were used (both P<0.001). Early postoperative serum uric acid was a better predictor than serum creatinine(P<0.001). Conclusion: The serum uric acid concentration within 12 hours after operation is an independent predictor of postoperative AKI in patients undergoing CABG, which could be used to identify patients at high risk for AKI.

First Report of Fusarium Wilt of Tobacco Caused by Fusarium kyushuense in China.

Tobacco (Nicotiana tabacum L.) is a leafy, annual, solanaceous plant grown commercially for its leaves. China accounts for more than 39.6% of total global tobacco production (3). In May 2012, seedlings of tobacco cv. Honghuadajinyuan in a Guiyang tobacco commercial field (Guizhou, China, 26.35° N, 106.42° E) developed symptoms of severe wilting, chlorosis, and stunting. The main stem and taproot exhibited reddish to light brown vascular discoloration; further progression of these symptoms eventually caused mortality of infected seedlings. To isolate the causal agent, necrotic tissues from the symptomatic root were placed on potato dextrose agar (PDA) and incubated at 25°C in darkness. Colonies with white to rose mycelia and red-brown colony colors developed on PDA after 5 days of incubation. Microconidia were abundant, straight or slightly curved, clavate, 0- to 3-septate, and 7.5 to 20.0 × 2.5 to 5.0 µm. Macroconidia were straight or slightly curved, slender, 3- to 5-septate, and 25.0 to 45.0 × 3.3 to 5.0 µm. Based on the observed colony attributes, growth patterns, absence of chlamydospores, micro- and macro-spore attributes (1), and PCR amplification (using primers ITS1/4) combined with translation elongation factor primers (EF1/2) (2), the fungus was identified as F. kyushuense O'Donnell & T. Aoki. Sequence of ITS1-5.8s-ITS2 region of rDNA (GenBank Accession No. JX235957) exactly matched the sequences of F. kyushuense accession AB587020.1 (100% similarity). Analysis of the elongation factor (EF-1alpha) gene of the fungus (JX658565) resulted in a 99% match for F. kyushuense accession AB674297.1. Pathogenicity of the fungus was confirmed by performing Koch's postulate as follows. Pure cultures of the fungus F. kyushuense obtained from symptomatic tissues of tobacco seedlings were grown on PDA for 6 days. Tobacco plants to be used in pathogenicity tests were germinated and grown on potting soils in a plastic container. Additional fertilization was supplied by adding 0.2 g/L of 20-20-20 (N-P-K) in the float water. When seedlings got 6-leaf stage, they were ready for pathogenicity tests. Spores harvested from these culture plates were suspended in sterile distilled water, adjusted to a concentration of 1 × 104 conidia/ml, and inoculated by irrigating 10 ml of the conidia suspension onto roots of each of the 12 tobacco seedlings with 6-leaf stage. A group of 12 seedlings of the same age treated with sterile water served as control. Inoculated seedlings were maintained at 25°C, 100 µE m-2.s-1, relative humidity >70%, and 16 h light per day, and monitored for 9 days for symptom development. Seedlings inoculated with conidia developed disease symptoms with roots with vascular discoloration of roots whereas control seedlings remained symptomless. F. kyushuense was reisolated from the symptomatic seedlings 9 days after inoculation. F. kyushuense has also been isolated from rice seeds in China (4), and from diseased wheat in Japan (1). The common tobacco Fusarium disease reported in China was caused by F. oxysporium f. sp. nicotianae. However, to the best of our knowledge, this is the first report of F. kyushuense causing wilt on tobacco in China and the disease must be considered in existing disease management practices. References: (1) T. Aoki and K. O'Donnell. Mycoscience. 39:1, 1998. (2) D. M. Geiser et al. Eur. J. Plant Pathol. 110:473, 2004. (3) US Census Bureau. Foreign Trade Statistics. Washington DC, 2005. (4) Z. H. Zhao and G. Z. Lu. Mycotaxon. 102:119, 2007.

Molecular characterization, expression pattern and association analysis of the porcine BTG2 gene.

B-cell translocation gene 2 (BTG2), a member of the B-cell translocation gene family with anti-proliferative properties, have been characterized to be involved in cell growth, differentiation and survival. In this study, we cloned the full length sequences of cDNA and genomic DNA of BTG2 gene from the porcine skeletal muscle. Spatial expression analysis showed that the porcine BTG2 gene is expressed predominantly in muscle. Temporal expression analysis in longissimus dorsi muscle demonstrated that the expression of BTG2 gene has the highest expression at 60 days old in Large White while with a peak expression at 120 days old in Meishan. Temporal analysis also revealed that the expression of BTG2 gene is generally higher in Large White than in Meishan at all the developmental stages tested (65 days of conception and 3, 35, 60, 120, and 180 days of postnatal). A single nucleotide polymorphism (G417C) in the intron of BTG2 gene was then detected by PCR-RFLP in Large White × Meishan F2 resource population and association analysis suggested that this polymorphic site had significant association (P < 0.05) with the buttock fat thickness, fat percentage, lean muscle percentage, ratio of lean to fat and carcass length.

Enhanced tumor suppression in vitro and in vivo by co-expression of survivin-specific siRNA and wild-type p53 protein.

The development of malignant prostate cancer involves multiple genetic alterations. For example, alterations in both survivin and p53 are reported to have crucial roles in prostate cancer progression. However, little is known regarding the interrelationships between p53 and survivin in prostate cancer. Our data demonstrate that the expression of survivin is inversely correlated with that of wtp53 protein (r(s)=0.548) in prostate cancer and in normal prostate tissues. We have developed a therapeutic strategy, in which two antitumor factors, small interfering RNA-survivin and p53 protein, are co-expressed from the same plasmid, and have examined their effects on the growth of PC3, an androgen-independent prostate cancer cell line. When p53 was expressed along with a survivin-specific short hairpin RNA (shRNA), tumor cell proliferation was significantly suppressed and apoptosis occurred. In addition, this combination also abrogated the expression of downstream target molecules such as cyclin-dependent kinase 4 and c-Myc, while enhancing the expression of GRIM19. These changes in gene expression occurred distinctly in the presence of survivin-shRNA/wtp53 compared with control or single treatment groups. Intratumoral injection of the co-expressed construct inhibited the growth and survival of tumor xenografts in a nude mouse model. These studies revealed evidence of an interaction between p53 and survivin proteins plus a complex signaling network operating downstream of the wtp53-survivin pathway that actively controls tumor cell proliferation, survival and apoptosis.

An alternative interpretation of nanobacteria-induced biomineralization.

The reported isolation of nanobacteria from human kidney stones raises the intriguing possibility that these microorganisms are etiological agents of pathological extraskeletal calcification [Kajander, E. O. & Ciftçioglu, N. (1998) Proc. Natl. Acad. Sci. USA 95, 8274-8279]. Nanobacteria were previously isolated from FBS after prolonged incubation in DMEM. These bacteria initiated biomineralization of the culture medium and were identified in calcified particles and biofilms by nucleic acid stains, 16S rDNA sequencing, electron microscopy, and the demonstration of a transferable biomineralization activity. We have now identified putative nanobacteria, not only from FBS, but also from human saliva and dental plaque after the incubation of 0.45-microm membrane-filtered samples in DMEM. Although biomineralization in our "cultures" was transferable to fresh DMEM, molecular examination of decalcified biofilms failed to detect nucleic acid or protein that would be expected from growth of a living entity. In addition, biomineralization was not inhibited by sodium azide. Furthermore, the 16S rDNA sequences previously ascribed to Nanobacterium sanguineum and Nanobacterium sp. were found to be indistinguishable from those of an environmental microorganism, Phyllobacterium mysinacearum, that has been previously detected as a contaminant in PCR. Thus, these data do not provide plausible support for the existence of a previously undiscovered bacterial genus. Instead, we provide evidence that biomineralization previously attributed to nanobacteria may be initiated by nonliving macromolecules and transferred on "subculture" by self-propagating microcrystalline apatite.

Restriction fragment length polymorphism caused by a deletion within the human c-abl gene (ABL).

A restriction fragment length polymorphism at the human c-abl locus (ABL) has been detected in 67 unrelated individuals by agarose gel electrophoresis and Southern blot hybridization using 32P-labeled v-abl probes. This polymorphism is generated by the existence of two alleles, a and b, which are in Hardy-Weinberg equilibrium, with frequencies of 94.8% and 5.2%, respectively. The minor allele, b, is due to a deletion of about 500 base pairs in an intron located downstream of the codon for the phosphate-acceptor tyrosine residue of the c-abl gene product.

Restriction fragment length polymorphism of the human c-fms gene.

By using blot hybridization with a v-fms probe, a polymorphism for EcoRI, HindIII, and BamHI restriction endonuclease sites associated with the human c-fms locus was observed in a random adult population. This restriction fragment length polymorphism can be explained on the basis of the existence of two alleles, a and b, and is due to a short (congruent to 500 base pairs) deletion characteristic of allele a. The distribution in the analyzed population (48 unrelated individuals) is 23% heterozygotes ab, 75% homozygotes bb, and 2% homozygotes aa. Though the inheritance of this polymorphism follows a Mendelian pattern, the children from couples ab X bb are of the following genotype: 74% ab and 26% bb. These deviations from the expected frequencies of 50% suggest a selective pressure in favor of heterozygotes.

An EcoRI restriction fragment length polymorphism (RFLP) in the human c-erb A locus.

An EcoRI restriction fragment length polymorphism (RFLP) was detected in the 3' end of the locus of the c-erb-A proto-oncogene. The frequency of the rarer allele was around 3.0% in a normal population of 107 unrelated individuals. This frequency did not significantly differ in DNA samples from patients with breast tumors or acute leukemias.