Prevalence and Antimicrobial Resistance Diversity of Salmonella Isolates in Jiaxing City, China.

Nontyphoidal Salmonella (NTS) is a cause of foodborne diarrheal diseases worldwide. Important emerging NTS serotypes that have spread as multidrug-resistant high-risk clones include S. Typhimurium monophasic variant and S. Kentucky. In this study, we isolated Salmonella in 5019 stool samples collected from patients with clinical diarrhea and 484 food samples. Antibiotic susceptibility testing and whole-genome sequencing were performed on positive strains. The detection rates of Salmonella among patients with diarrhea and food samples were 4.0% (200/5019) and 3.1% (15/484), respectively. These 215 Salmonella isolates comprised five main serotypes, namely S. Typhimurium monophasic variant, S. Typhimurium, S. London, S. Enteritidis, and S. Rissen, and were mainly resistant to ampicillin, tetracycline, chloramphenicol, and trimethoprim/sulfamethoxazole. The MDR rates of five major serotypes were 77.4%, 56.0%, 66.7%, 53.3%, and 80.0%, respectively. The most commonly acquired extended-spectrum ß-lactamase-encoding genes were blaTEM-1B, blaOXA-10, and blaCTX-M-65. The S. Typhimurium monophasic variant strains from Jiaxing City belonged to a unique clone with broad antibiotic resistance. S. Kentucky isolates showed the highest drug resistance, and all were MDR strains. The discovery of high antibiotic resistance rates in this common foodborne pathogen is a growing concern; therefore, ongoing surveillance is crucial to effectively monitor this pathogen.

Analysis on time delay of tuberculosis among adolescents and young adults in Eastern China.

Background: Tuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults. Methods: All notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China's TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored. Results: From January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05-1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28-2.26), passive case finding (AOR: 1.46, 95% CI: 1.07-1.98) and retreatment (AOR: 1.52, 95% CI: 1.11-2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53-0.90) and non-students (AOR: 0.83, 95% CI: 0.71-0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29-1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32-1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30-1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78-1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59-0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before. Conclusion: In general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.

Exploring the enigmatic association between PNLIP variants and risk of chronic pancreatitis in a large Chinese cohort.

BACKGROUND & AIMS: Protease-sensitive PNLIP variants were recently associated with chronic pancreatitis (CP) in European populations. The pathological mechanism yet remains elusive. Herein, we performed a comprehensive genetic and functional analysis of PNLIP variants found in a large Chinese cohort, aiming to further unravel the enigmatic association of PNLIP variants with CP. METHODS: All coding and flanking intronic regions of the PNLIP gene were analyzed for rare variants by targeted next-generation sequencing in 1082 Chinese CP patients and 1196 controls. All novel missense variants were subject to analysis of secretion, lipase activity, and proteolytic degradation. One variant was further analyzed for its potential to misfold and induce endoplasmic reticulum (ER) stress. p.F300L, the most common PNLIP variant associated with CP, was used as a control. RESULTS: We identified 12 rare heterozygous PNLIP variants, with 10 being novel. The variant carrier frequency did not differ between the groups. Of them, only the variant p.A433T found in a single patient was considered pathologically relevant. p.A433T exhibited increased susceptibility to proteolytic degradation, which was much milder than p.F300L. Interestingly, both variants exhibited an increased tendency to misfold, leading to intracellular retention as insoluble aggregates, reduced secretion, and elevated ER stress. CONCLUSIONS: Our genetic and functional analysis of PNLIP variants identified in a Chinese CP cohort suggests that the p.A433T variant and the previously identified p.F300L variant are not only protease-sensitive but also may be potentially proteotoxic. Mouse studies of the PNLIP p.F300L and p.A433T variants are needed to clarify their role in CP.

The Association Between Environmental Cadmium Exposure and Parathyroid Hormone Levels.

Cadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However, whether cadmium exposure affect PTH level is not completely understood. In this study, we observed the association between environmental cadmium exposure and PTH levels in a Chinese population. A ChinaCd study was performed in China in 1990s which included 790 subjects living in heavily, moderately and low cadmium polluted area. 354 of them (121 men and 233 women) also had the data of serum PTH. The cadmium levels in blood (BCd) and urine (UCd) were determined by flame atomic absorption spectrometry. Serum PTH was detected by immunoradiometric assay. Renal function was assessed based on urinary N-acetyl-ß-d-glucosaminidase (UNAG), ß2-microglobulin (UBMG) and urinary albumin (UALB). The median BCd and UCd levels were 4.69 µg/L and 5.50 µg/g creatinine. The BCd, UCd, UNAG, UBMG and UALB levels in subjects with low PTH (< 5.0 ng/L) were significantly higher than those with PTH ≥ 5.0 ng/L (p < 0.05 or p < 0.01). Spearman correlation analysis also showed that UCd level was negatively correlated to PTH levels (r = -0.17, p = 0.008) in women. A weak correlation was also observed between PTH level and BCd in women (r = -0.11, p = 0.09) and UBMG in total population (r = -0.114, p = 0.07). Univariable and mutivariable logistic regression analysis both demonstrated that high BCd (> 10 µg/L) (odds ratio (OR) = 2.26, 95% confidence interval (CI):1.10-4.63; OR = 2.36, 95%CI: 1.11-5.05) and UCd level (> 20 µg/g cr) (OR = 2.84, 95% CI:1.32-6.10; OR = 2.97, 95%CI: 1.25-7.05) were associated with high risk of low PTH. Our data showed that environmental cadmium exposure was associated with low PTH level.

C-C Motif Chemokine Ligand 5 (CCL5) Promotes Irradiation-Evoked Osteoclastogenesis.

The imbalance that occurs in bone remodeling induced by irradiation (IR) is the disruption of the balance between bone formation and bone resorption. In this study, primary osteocytes (OCYs) of femoral and tibial origin were cultured and irradiated. It was observed that irradiated OCY showed extensive DNA damage, which led to the initiation of a typical phenotype of cellular senescence, including the secretion of senescence-associated secretory phenotype (SASP), especially the C-C motif chemokine ligand 5 (CCL5). In order to explore the regulation of osteoclastogenic potential by IR-induced senescent OCYs exocytosis factor CCL5, the conditioned medium (CM) of OCYs was co-cultured with RAW264.7 precursor cells. It was observed that in the irradiated OCY co-cultured group, the migration potential increased compared with the vehicle culture group, accompanied by an enhancement of typical mature OCs; the expression of the specific function of enzyme tartrate-resistant acid phosphatase (TRAP) increased; and the bone-destructive function was enhanced. However, a neutralizing antibody to CCL5 could reverse the extra-activation of osteoclastogenesis. Accordingly, the overexpression of p-STAT3 in irradiated OCY was accompanied by CCL5. It was concluded that CCL5 is a potential key molecule and the interventions targeting CCL5 could be a potential strategy for inhibiting osteoclastogenesis and restoring bone remodeling.

Characteristics of Two mcr-1-Harboring IncHI2 Plasmids from Clinical Salmonella Isolates in Jiaxing City.

Salmonella is a primary cause of foodborne diseases, and the increasing prevalence of mcr-1-carrying plasmids, which confer colistin resistance to Salmonella, poses significant global health concerns. As the frequency of occurrence of the mcr-1 gene is increasing globally, we studied the prevalence of mcr-1 in clinical Salmonella isolates by analyzing 195 clinical strains isolated in 2020. Of the 195 Salmonella isolates, 41 isolates were resistant to colistin. We found mcr-1 in two strains (Salmonella Typhimurium ZJJX20006 and Salmonella Kentucky ZJJX20014), which we analyzed in detail via whole-genome sequencing and antibiotic susceptibility testing. Two strains displayed resistance to ampicillin, ampicillin-sulbactam, tetracycline, chloramphenicol, and cotrimoxazole, while ZJJX20006 displayed resistance to colistin and ZJJX20014 was sensitive. Genomic analysis revealed that these strains had plasmid-encoded mcr-1 in IncHI2 plasmids, which were not similar to the mcr-1-IncX4 identified in 2016. These two strains also harbored other drug resistance genes, including blaOXA-1 and blaCTX-M-14. Our findings may help clarify the molecular mechanisms of mcr-1 dissemination among Salmonella strains in Jiaxing City and offer insights into the evolution of mcr-1 in Salmonella.

Radiation Induces Bone Microenvironment Disruption by Activating the STING-TBK1 Pathway.

Background and Objectives: Damage to normal bone tissue following therapeutic irradiation (IR) represents a significant concern, as IR-induced bone microenvironment disruption can cause bone loss and create a more favorable environment for tumor metastases. The aim of the present study was to explore the cellular regulatory mechanism of IR-induced bone microenvironment disruption to effectively prevent radiotherapy-associated adverse effects in the future. Materials and Methods: In this study, a mouse model of local IR was established via local irradiation of the left hind limb of BALB/c mice with 12 Gy X-rays, and an in vitro osteocyte (OCY) model was established by exposing osteocyte-like MLO-Y4 cells to 2, 4, and 8 Gy irradiation to analyze multicellular biological injuries and cellular senescence. Small interfering RNA (siRNA) transfection at the cellular level and a selective antagonist intervention C-176 at the animal level were used to explore the potential role of the stimulator of interferon genes (STING) on IR-induced bone microenvironment disruption. Results: The results showed that 12 Gy local IR induces multicellular dysfunction, manifested as ascension of OCYs exfoliation, activation of osteoclastogenesis, degeneration of osteogenesis and fate conversion of adipogenesis, as well as cellular senescence and altered senescence-associated secretory phenotype (SASP) secretion. Furthermore, the expression of STING was significantly elevated, both in the primary OCYs harvested from locally irradiated mice and in vitro irradiated MLO-Y4 cells, accompanied by the markedly upregulated levels of phosphorylated TANK-binding kinase 1 (P-TBK1), RANKL and sclerostin (SOST). STING-siRNA transfection in vitro restored IR-induced upregulated protein expression of P-TBK1 and RANKL, as well as the mRNA expression levels of inflammatory cytokines, such as IL-1α, IL-6 and NF-κB, accompanied by the alleviation of excessive osteoclastogenesis. Finally, administration of the STING inhibitor C-176 mitigated IR-induced activation of osteoclastogenesis and restraint of osteogenesis, ameliorating the IR-induced biological damage of OCYs, consistent with the inhibition of P-TBK1, RANKL and SOST. Conclusions: The STING-P-TBK1 signaling pathway plays a crucial role in the regulation of the secretion of inflammatory cytokines and osteoclastogenesis potential in IR-induced bone microenvironment disruption. The selective STING antagonist can be used to intervene to block the STING pathway and, thereby, repair IR-induced multicellular biological damage and mitigate the imbalance between osteoclastogenesis and osteoblastgenesis.

Iodine-125 brachytherapy suppresses tumor growth and alters bone metabolism in a H1299 xenograft mouse model.

The present study aimed to investigate the efficacy of Iodine-125 (I-125) brachytherapy in a mouse model of non-small cell lung cancer, to further explore the efficacy and appropriate method of implantation of the I-125 radioactive seed. This study also aimed to determine the impact of brachytherapy on bone metabolism. A total of 18 mice were used to establish H1299 xenograft models, and were randomly assigned to three groups. These included non-radioactive seed implantation (Sham IM), fractionated I-125 seed implantation (Fractionated IM) and single I-125 seed implantation (Single IM) groups. Mice were euthanized after 28 days of implantation. H&E staining, Ki67 immunohistochemistry, CD31 morphometric analysis and TUNEL immunofluorescence assays were respectively used to determine the histopathological changes, proliferation, micro-angiogenesis and apoptosis of tumors. In addition, bone volume and microstructure were evaluated using trabecular bone area (Tb.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and cortical thickness. Bone metabolic status was analyzed using histomorphometric staining of tartrate-resistant acid phosphate (TRAP) and alkaline phosphatase (ALP) expression in the femur, and using an ELISA assay to determine the expression of C-telopeptide of type 1 collagen (CTX-1) and procollagen type 1 n-terminal propeptide (P1NP) in the serum. Moreover, reverse transcription-quantitative PCR and western blotting were carried out for the analysis of bone remodeling-related gene expression in the bone tissue. Results of the present study demonstrated that compared with the Sham IM group, both the I-125 seed implantation groups, including Fractionated IM and Single IM, demonstrated significant therapeutic effects in both tumor volume and weight. More specifically, the most significant therapeutic effects on tumor inhibition were observed in the Fractionated IM group. Results of Ki67 and CD31 immunohistochemical staining suggested a notable reduction in tumor cell proliferation and micro-angiogenesis, and results of the TUNEL assay demonstrated an increase in tumor cell apoptosis. Although the cortical bone appeared thinner and more fragile in both I-125 seed implantation groups, no notable adverse changes in the morphology of the cancellous bone were observed, and the index of Tb.Ar, Tb.Th and Tb.n was not significantly different among Sham IM and I-125 implantation groups. However, alterations in bone metabolism were characterized by a decrease in CTX-1 and P1NP expression, accompanied by an increase in TRAP activity and a decrease in ALP activity. Results of the present study also demonstrated the notable suppression of osteocalcin and runt-related transcription factor 2. I-125 seed implantation may be an effective and safe antitumor strategy. Moreover, the use of fractionated implantation patterns based on tumor shape exhibited improved therapeutic effect on tumor suppression when the total number of I-125 seeds was equivalent along with reduced complications associated with bone loss.

Preclinical mouse model of a misfolded PNLIP variant develops chronic pancreatitis.

OBJECTIVE: Increasing evidence implicates mutation-induced protein misfolding and endoplasm reticulum (ER) stress in the pathophysiology of chronic pancreatitis (CP). The paucity of animal models harbouring genetic risk variants has hampered our understanding of how misfolded proteins trigger CP. We previously showed that pancreatic triglyceride lipase (PNLIP) p.T221M, a variant associated with steatorrhoea and possibly CP in humans, misfolds and elicits ER stress in vitro suggesting proteotoxicity as a potential disease mechanism. Our objective was to create a mouse model to determine if PNLIP p.T221M causes CP and to define the mechanism. DESIGN: We created a mouse model of Pnlip p.T221M and characterised the structural and biochemical changes in the pancreas aged 1-12 months. We used multiple methods including histochemistry, immunostaining, transmission electron microscopy, biochemical assays, immunoblotting and qPCR. RESULTS: We demonstrated the hallmarks of human CP in Pnlip p.T221M homozygous mice including progressive pancreatic atrophy, acinar cell loss, fibrosis, fatty change, immune cell infiltration and reduced exocrine function. Heterozygotes also developed CP although at a slower rate. Immunoblot showed that pancreatic PNLIP T221M misfolded as insoluble aggregates. The level of aggregates in homozygotes declined with age and was much lower in heterozygotes at all ages. The Pnlip p.T221M pancreas had increased ER stress evidenced by dilated ER, increased Hspa5 (BiP) mRNA abundance and a maladaptive unfolded protein response leading to upregulation of Ddit3 (CHOP), nuclear factor-κB and cell death. CONCLUSION: Expression of PNLIP p.T221M in a preclinical mouse model results in CP caused by ER stress and proteotoxicity of misfolded mutant PNLIP.

Epidemiological investigation of a cluster of COVID-19 in badminton venues / 预防医学

Objective@#To perform an epidemiological survey of the first case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Pinghu City of Jiaxing City, Zhejiang Province on March 13, 2022, so as to provide insights into the management of coronavirus disease (COVID-19) epidemics. @*Methods@#According to the requirements of the Protocol on Prevention and Control of COVID-19 (8th Edition), epidemiological investigations were performed among 39 cases with SARS-CoV-2 infections in Pinghu City from March 13 to 20, 2022. Cases' demographics, clinical symptoms, history of immunization and exposure were collected, and close contacts were identified. Pharyngeal swabs were sampled from infected cases for detection of SARS-CoV-2 nucleic acid and whole-genome sequencing, and the source of infection and transmission route were investigated. @*Results@#The index case for this COVID-19 epidemic was an imported case from Shanghai Municipality, who infected 6 persons via aerosol transmission when playing in the badminton venue of Pinghu National Fitness Center on March 9; subsequently, one of these infected cases infected another 18 persons when playing in the badminton venue of Jiadian Village Resident's Fitness Center in Zhapu Township on March 12. Sixteen confirmed cases were reported, and all cases were mild; another 23 asymptomatic cases were diagnosed, with no death reported. This epidemic occurred from March 11 to 20, with 3 generations of spread and a median incubation period of 3 days. The SARS-CoV-2 infected cases had a median age of 33.5 (interquartile range, 12.0) years and included 36 cases with a history of COVID-19 vaccination. There were 16 cases with fever, cough, runny nose and sore throat, and 13 cases with imaging features of pneumonia. The effective reproductive number (Rt) of the COVID-19 epidemic was 7.73 at early stage, and was less than 1 since March 21. Whole-genome sequencing identified Omicron BA.2 variant among 33 cases, which had high homology with the index cases. @*Conclusion@#This epidemic was a cluster of COVID-19 caused by imported Omicron BA.2 variant infection from Shanghai Municipality, and the COVID-19 transmission was mainly caused by indoor aerosols.

Direct and Rapid Identification of Vibrio Cholerae Serogroup and Toxigenicity by a Novel Multiplex Real-Time Assay.

Molecular diagnostic assays for cholera detection have superior sensitivity to conventional assays and are now being accepted as the new standard method, especially the real-time PCR/RT-PCR. However, limited throughput capacity and long detection duration prevent them from detecting more specimens and more targets in one turnaround time simultaneously. In this study, we utilized nucleic acid extraction-free, direct RT-PCR and high-speed amplification to develop a novel multiplex assay, a quadplex direct one-tube real-time RT-PCR assay, for rapid detection of the serogroup and cholera toxin toxigenicity of Vibrio cholerae targeting the epsM, ctxA, rfb-O1, and rfb-O139 genes. Performance of the multiplex assay was evaluated by comparison with the monoplex real-time PCR assay according to the China Cholera Prevention Manual. Detection data from clinical specimens showed that the new assay had good diagnostic sensitivities for epsM (100%, n = 301), ctxA (100%, n = 125), rfb-O1 (100%, n = 85), and rfb-O139 (97.87%, n = 49). Analysis of the analytical sensitivities with serial dilutions of positive standards showed that the detection limits of the new assay for Vibrio cholerae epsM,ctxA,rfb-O1, and rfb-O139 were up to 200, 590, 115, and 1052 copies per mL lower than the monoplex real-time PCR (910, 345, and 1616 copies/mL respectively, for ctxA,rfb-O1, and rfb-O139). The results indicate that the multiplex assay is a rapid, sensitive, specific, and easy-to-use detection tool for Vibrio cholerae, especially suitable for rapid identification and screening detection of mass specimens.

Celecoxib-mediated attenuation of non-alcoholic steatohepatitis is potentially relevant to redistributing the expression of adiponectin receptors in rats.

Pharmacological inhibition of cyclooxygenase-2 (COX-2) activity ameliorated the severity of non-alcoholic steatohepatitis (NASH) rats. It is not completely understood that the role of COX-2 inhibitor celecoxib on adiponectin receptors (Adipo-R1/R2) expression in different tissues in NASH rats. Sprague-Dawley male NASH rats induced by a high-fat diet (HFD) were administrated with or without celecoxib for 8 weeks. Biochemical parameters of liver function, glucose, and lipid metabolism, and the levels of adiponectin, tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2) in the serum or liver were collected according to the standard protocols. The mRNA and protein levels of Adipo-R1, Adipo-R2, and COX-2 in the liver, muscle, and visceral fat were performed by quantitative real-time polymerase chain reaction (q-PCR) and Western blot analysis, respectively. The results showed that celecoxib ameliorated the various clinical indicators and pathological characteristics in the NASH rats, including body weight, liver function, liver index, and redox activities in serum and hepatic samples. The serum concentrations of adiponectin and TNF-α and PGE2 were negatively correlated. As expected, these ameliorative effects of celecoxib were associated with the gene and protein levels up-regulation of Adipo-R1, Adipo-R2 in the liver and visceral fat tissues, and seeming to be compensatory down-regulation expression in muscle tissues (P <0.05). Additionally, COX-2 protein expression was negatively correlated with serum adiponectin levels, protein expression of adiponectin receptors from the liver and visceral fat, conversely, positively correlated with those from the muscle. Our current study demonstrate that celecoxib might effectively alleviate NASH rats in a unique manner closely relevant to redistributing the expression of adiponectin receptors in the liver, visceral fat, and muscle. However, the precise molecular mechanism needs further study.

Low levels of cadmium exposure affect bone by inhibiting Lgr4 expression in osteoblasts and osteoclasts.

BACKGROUND: Cadmium exposure is associated with bone loss. However, the mechanisms involved have not yet been fully understood. Leucine-rich repeat containing GPCR-4 (LGR4) can bind with the receptor activator of nuclear factors κB ligand (RANKL) and inhibit osteoclast formation. In addition, Lgr4 plays an important role in maintaining osteoblast activity. In the present study the effect of cadmium exposure on bone was investigated in terms of Lgr4 expression. METHODS: Raw 264.7 cells and primary osteoblasts were exposed to cadmium (0-60 nM/L). The effects of cadmium on osteoclast formation and osteoblast activity were investigated. Osteoclast differentiation-related (Traf6, NFATc1) and osteoblast-related (RANKL; osteoprotegerin, OPG) gene and protein expression were determined. Lgr4 expression in osteoclasts and osteoblasts were also determined. A rat model was established to show the effects of cadmium (50 mg/L) on bone loss and Lgr4 expression in vivo. RESULTS: Cadmium exposure inhibited osteoblast activities and stimulated osteoclast formation. Cadmium exposure also inhibited Lgr4 expression in both osteoclasts and osteoblasts. Low dose of RANKL added to the culture medium could promote osteoclast formation in cadmium-pretreated RAW264.7 cells. Blocking Lgr4 in osteoclasts only slightly inhibited cadmium-induced osteoclast formation in cadmium-pretreated RAW264.7 cells. Cadmium significantly upregulated the AKT/ERK signaling pathway. An in vivo study showed that cadmium exposure promoted osteoclast formation and inhibited Lgr4 expression. CONCLUSIONS: Our data indicates that cadmium may induce bone loss by inhibiting Lgr4-related bone formation and promoting Lgr4-related osteoclast formation.

Development and Application of a Multiplex Fluorescent PCR for Shigella Detection and Species Identification.

This study was to develop a multiplex fluorescent PCR for Shigella detection and species identification. Five primer pairs for Shigella detection and species identification were designed by Primer Premier 5.0. The multiplex fluorescent PCR was optimized by varying single parameter while other parameters were maintained. The multiplex fluorescent PCR assay could correctly detect Shigella and identify four Shigella species with a detection limits of 10 pg genomic DNA per reaction. Testing different strains and clinical samples confirmed the sensitivity and specificity of the multiplex fluorescent PCR. The newly developed multiplex fluorescent PCR assay is simple, sensitive and specific for Shigella detection and species identification. It has a potential to be used in routine Shigella detection and species identification in clinical laboratories.

The association between hemoglobin level and osteoporosis in a Chinese population with environmental lead and cadmium exposure.

Low hemoglobin (Hb) level or anemia is associated with osteoporosis and bone fracture. Cadmium (Cd) and lead (Pb) exposure are also risk factors of osteoporosis and anemia. However, the role of anemia in Cd/Pb related bone loss remains unclear. The aim of present study was to investigate the association between Hb level and bone loss in a population with environmental lead and cadmium exposure. One hundred and ninety-four women and 108 men with different levels of Cd/Pb exposure were included in our study. The Cd/Pb exposure was determined using graphite-furnace atomic absorption spectrometry. Forearm bone mineral density (BMD) was determined by peripheral dual-energy X-ray absortiometry. Hb concentration was determined using an automatic blood cellcounter. A logistic model was established to predict the risk of osteoporosis. The BMDs of women that had the highest quartile BCd and BPb were markedly lower than that with the lowest quartile (p < 0.05). The BMD and the prevalence of osteoporosis in men with anemia were lower and higher than that with normal Hb (p < 0.05), respectively. In men, age, BPb and anemia were independent risk factors for osteoporosis. The odds ratio (OR) of men with anemia was 11.28 (95%confidence interval (CI):1.94-65.54) and 19.56 (95%CI: 2.98-128.78) compared to those with normal Hb after adjusting for potential cofounders. No such association was found in women. The area under the curve was 0.88 (95%CI: 0.82-0.96) in predicting osteoporosis using the logistic model in men. Linear discriminant analysis also showed that 90.7% of osteoporosis was correctly classified. Our data show that anemia is associated with incident of osteoporosis in men but not in women that environmentally exposed to Pb and Cd.

First Identification and Limited Dissemination of mcr-1 Colistin Resistance in Salmonella Isolates from Jiaxing.

ABSTRACT: Salmonella, a major foodborne pathogen, causes severe gastrointestinal disease in people and animals worldwide. Plasmid-borne mcr-1, which confers colistin resistance in Salmonella, has significant epidemiological interest for public health safety. Here, we report the first evidence of mcr-1-mediated colistin resistance in one multidrug-resistant strain, 16062, from 355 Salmonella isolates collected for Jiaxing foodborne pathogen monitoring in Zhejiang Province from 2015 to 2019. In addition to colistin, 16062 displayed multidrug resistance to various antimicrobials (ß-lactams, quinolone, sulfonamide, florfenicol, ampicillin, streptomycin, nalidixic acid, aminoglycoside, and trimethoprim-sulfamethoxazole). The mcr-1-carrying IncX4 plasmid (p16062-MCR) in this study shares a conserved structure with other mcr-IncX4 plasmids. We found that other antimicrobial-resistance genes (aac(6')-Ib-cr, aadA1, aadA2, aph(3')-Ia, oqxA, oqxB, sul1, and cmlA1) are located on p16062-cmlA, an atypical IncHI2 plasmid, in isolate 16062. This is the first identification of transferable colistin resistance in a foodborne Salmonella isolate collected in Jiaxing City, the 5-year monitoring of which revealed limited dissemination. By determining the genetic features of the plasmid vehicle, the characteristics of transferable mcr genes circulating in isolates from Jiaxing are now clearer.

The Association Between Cadmium Exposure and Osteoporosis: A Longitudinal Study and Predictive Model in a Chinese Female Population.

Objective: The association between cadmium exposure and osteoporosis has been rarely reported in longitudinal studies. In this study, we investigated the association between osteoporosis and cadmium exposure and developed predictive models in women in a longitudinal cohort. Materials and Methods: In total, 488 women living in southeastern China were included at baseline (1998). Cadmium in blood (BCd) and urine (UCd) and also renal dysfunction biomarkers and bone mineral density (BMD) were determined both at baseline and follow-up. A total of 307 subjects were finally included after excluding subjects that did not have exposure or effect biomarkers. Osteoporosis was defined based on T score ≤ -2.5. Multiple linear regression and multivariate logistic analysis were used to show the association between baseline data and follow-up osteoporosis. Based on the identified associated factors, nomograms were developed to graphically calculate the individual risk of osteoporosis. Results: The baseline BMD in subjects with osteoporosis was significantly lower than that in subjects without osteoporosis (0.59 vs. 0.71 g/cm2, p < 0.05). The prevalence of low bone mass at baseline was higher in subjects with osteoporosis than in those without osteoporosis (23.5 vs. 7.2%, p = 0.001). Logistic regression analysis demonstrated that age [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.16-1.27], UCd (OR = 1.03, 95% CI: 1.002-1.06) and the presence of low BMD (OR = 3.84, 95% CI: 1.49-9.89) were independent risk factors for osteoporosis. For those subjects with normal baseline BMD, age, UCd, and baseline BMD were also independent risk factors for osteoporosis. The OR value was 1.16 (95% CI: 1.10-1.22) for age, 2.27 (95% CI: 1.03-4.99) for UCd > 10 µg/g creatinine, and 0.39 (95% CI: 0.21-0.72) for BMDbaseline. We developed two nomograms to predict the risk of osteoporosis. The area under the curve was 0.88 (95% CI: 0.84-0.92) for total population and was 0.88 (95% CI: 0.84-0.92) for subjects with normal baseline BMD, respectively. Conclusion: Baseline age, UCd, and BMD were associated with follow-up osteoporosis in women. Nomograms showed good performance in predicting the risk of osteoporosis.

Long-term safety and efficacy of the Resolute stent: 5-year results from the RESOLUTE China Registry: RESOLUTE China Registry 5-year outcomes.

AIMS: Long-term clinical outcome data for second-generation drug-eluting stents (DES) are critical for the assessment of safety and efficacy. Five-year results from the RESOLUTE China Registry are presented in this report. METHODS AND RESULTS: The RESOLUTE China Registry is a prospective, multicentre, observational study for all-comers requiring coronary stent implantation. The primary endpoint was target lesion failure (TLF) at one year, and the main secondary endpoint was definite or probable stent thrombosis at one year. Additional secondary endpoints assessed up to 5 years include rates of all deaths, target vessel myocardial infarction (TVMI) and target lesion revascularisation (TLR). A total of 1,800 patients were enrolled from December 2010 to March 2012 at 30 sites in China and implanted with Resolute DES. At 5 years, TLF was 9.8%, TVMI 3.2%, TLR 4.6% and very late stent thrombosis 0.5%. Results of pre-specified subgroup analyses show 5-year TLF rates of 14.3% for diabetics and 13.4% for patients with chronic total occlusions. CONCLUSIONS: The RESOLUTE China Registry is the largest study of Asian patients treated with second-generation Resolute DES. Clinical outcomes illustrate a robust safety and efficacy profile of Resolute DES in a real-word Asian population, including favourable performance in complex patient subsets.

Analysis of Risk Factors and Establishment of a Prediction Model for Endoscopic Primary Bile Reflux: A Single-Center Retrospective Study.

Background: Endoscopic primary bile reflux is one of the main diagnostic criteria for bile reflux gastritis (BRG). Presently, the risk factors and prediction models of endoscopic primary bile reflux (EPBR) in gastropathy patients who cannot or will not undergo endoscopy due to contraindications are not clear. Thus, this study aimed to evaluate the risk factors of EPBR and to establish and verify a prediction model. Methods: A series of 844 patients (564 subjects with EPBR and 280 control subjects) were retrospectively selected for this study and divided into a training set (n = 591) and a validation set (n = 253) according to the usual ratio of 70:30% for the subsequent internal validation of the logistic regression model for EPBR. Fifteen parameters that might affect the occurrence of EPBR were collected. Subsequently, univariate and stepwise logistic regression analyses were introduced to reveal the risk factors and the multivariate prediction model. An R package was dedicated to the corresponding internal validation of the EPBR model. Results: The univariate analysis showed that gender, age, smoking, Helicobacter pylori (H. pylori) infection status, metabolic syndrome (MS), non-steroidal anti-inflammatory drugs (NSAIDs) use history, and previous medical histories of chronic liver diseases, cholelithiasis, and erosive gastritis were statistically significant between the two groups (P < 0.05). Multivariate regression described that being a male [OR (95%confidence interval (CI)) = 2.29 (1.50-3.50), P < 0.001], age≥45 years old [OR (95% CI) = 4.24 (2.59-6.96), P < 0.001], H. pylori infection status [OR (95% CI) = 2.34 (1.37-4.01), P = 0.002], MS [OR (95% CI) = 3.14 (1.77-5.54), P < 0.001], NSAIDs use history [OR (95% CI) = 1.87 (1.03-3.40), P = 0.04], cholelithiasis history [OR (95% CI) = 3.95 (2.18-7.18), P < 0.001] and erosive gastritis history [OR (95% CI) = 6.77 (3.73-12.29), P < 0.001] were the risk factors for the occurrence of EPBR. Based on the results of these risk factors, an EPBR prediction model with an adequate calibration and excellent discrimination was established [area under the curve (AUC): 0.839, 95% CI = 0.806-0.872]. Conclusions: Being a male, age ≥ 45 years old, H. pylori infection, histories of MS, NSAIDs use, cholelithiasis, and erosive gastritis appear to be the risk factors for EPBR, and our favorable prediction model might be an option for the prediction of EPBR.

Effects of I-125 seeds combined with anlotinib on tumor growth and bone metabolism in A549 tumor-bearing mice.

PURPOSE: This study aimed to investigate the therapeutic potential of tumor suppression and mechanism for different implantation modes of iodine-125 (I-125) seeds irradiation in a mice xenograft model, and its skeletal complications. MATERIALS AND METHODS: A total of 24 mice carrying A549 lung tumor-derived xenografts were randomly assigned to four groups, including non-radioactive (sham) seeds implantation, I-125 seeds fractional implantation, I-125 seeds single implantation and I-125 seeds single implantation combined with anlotinib. Ki67 immunohistochemistry, TUNEL immunofluorescence and CD31 morphometric analysis were used to determine the proliferation index, rate of apoptotic cells and microvessel density, respectively. Additionally, the side effects on the skeletal system in mice treated with I-125 seeds implantation were evaluated by histomorphometric staining with tartrate-resistant acid phosphate (TRAP) and alkaline phosphatase (ALP) expression in femur, tartrate-resistant acid phosphatase 5b (TRACP-5b) and procollagen type I N-terminal propeptide (PINP) levels in serum were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The I-125 seeds single and fractionated implantation had similar therapeutic effects and complications when the total number of I-125 seeds was the same. A single implantation of I-125 seeds with or without anlotinib could analogously inhibit the tumor growth in xenografts mice, while the single implantation combined with anlotinib had more effective in tumor inhibition. The results of Ki67, TUNEL and CD31 staining confirmed an evident reduction in tumor cell proliferation and angiogenesis, as well as an increase in apoptosis. A relatively integrated bone metabolism was indicated after I-125 seeds single implantation with or without anlotinib, and the results were similar in I-125 seeds fractional implantation, including a reduction in the number of TRAP-positive cells and an increase in ALP expression level. Additionally, the serum TRACP-5b activity was decreased and the serum PINP concentration was increased following I-125 seeds implantation. CONCLUSIONS: Single and fractionated implantation pattern of I-125 radioactive seeds had similar therapeutic efficacy against tumor growth, while brachytherapy with I-125 seeds implantation may be an effective and safe treatment strategy for its potential protection against cancer treatment-induced bone loss.