[Contamination Characteristics and Ecological Risk of Antibiotics in Contaminated Sites of Typical Pharmaceutical Factories in China].

To understand the contamination characteristics and ecological risk of antibiotics in contaminated fields of pharmaceutical plants， samples of the surface soil， soil column， wastewater treatment process water， ground water， and residue dregs were collected from two typical antibiotic pharmaceutical plants in South and North China. A total of 87 commonly used antibiotics were quantified using ultrasound extraction-solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry. The results showed that a total of 31 antibiotics of five classes were detected in all types of samples， and the maximum concentrations at each sampling point in the surface soil， soil column， residue dregs， wastewater treatment process water， and groundwater were 420 ng·g-1， 595 ng·g-1， 139 ng·g-1， 1 151 ng·L-1， and 6.65 ng·L-1， respectively. Most of the antibiotics were found in the surface soil， showing a decreasing trend with the depth of the soil column. The ecological risk assessment indicated that sulfamethazine， sulfaquinoxaline， tetracycline， chlorotetracycline， and D-sorbitol were at higher risk. Improving the efficiency of antibiotic removal from pharmaceutical wastewater and preventing production shop leaks are effective measures of controlling antibiotic contamination into and around fields in pharmaceutical plants.

Gynura divaricata (L.) DC. promotes diabetic wound healing by activating Nrf2 signaling in diabetic rats.

THE ETHNOPHARMACOLOGICAL SIGNIFICANCE: Diabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.) DC. (GD), a traditional Chinese herbal medicine with hypoglycemic effects, has been proposed as a potential therapeutic agent for diabetic wound healing. However, the underlying mechanisms of its effects remain unclear. AIM OF THE STUDY: In this study, we aimed to reveal the effect and potential mechanisms of GD on accelerating diabetic wound healing in vitro and in vivo. MATERIALS AND METHODS: The effects of GD on cell proliferation, apoptosis, reactive oxygen species (ROS) production, migration, mitochondrial membrane potential (MMP), and potential molecular mechanisms were investigated in high glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) using CCK-8, flow cytometry assay, wound healing assay, immunofluorescence, DCFH-DA staining, JC-1 staining, and Western blot. Full-thickness skin defects were created in STZ-induced diabetic rats, and wound healing rate was tracked by photographing them every day. HE staining, immunohistochemistry, and Western blot were employed to investigate the effect and molecular mechanism of GD on wound healing in diabetic rats. RESULTS: GD significantly improved HUVEC survival, decreased apoptosis, lowered ROS production, restored MMP, improved migration ability, and raised VEGF expression. The use of Nrf2-siRNA completely abrogated these effects. Topical application of GD promoted angiogenesis and granulation tissue growth, resulting in faster healing of diabetic wounds. The expression of VEGF, CD31, and VEGFR was elevated in the skin tissue of diabetic rats after GD treatment, which upregulated HO-1, NQO-1, and Bcl-2 expression while downregulating Bax expression via activation of the Nrf2 signaling pathway. CONCLUSION: The findings of this study indicate that GD has the potential to serve as a viable alternative treatment for diabetic wounds. This potential arises from its ability to mitigate the negative effects of oxidative stress on angiogenesis, which is regulated by the Nrf2 signaling pathway. The results of our study offer valuable insights into the therapeutic efficacy of GD in the treatment of diabetic wounds, emphasizing the significance of directing interventions towards the Nrf2 signaling pathway to mitigate oxidative stress and facilitate the process of angiogenesis.

Synergistic impact of co-exposures to whole blood metals on chronic kidney disease in general US adults: a cross­sectional study of the National Health and Nutrition Examination Survey 2011-2020.

The impact of exposure to metals on chronic kidney disease (CKD) has only been investigated in two-way or single metal interactions in previous studies. We investigated the associations between five single metals in blood and their mixed exposure and CKD by using the machine learning approach. Relevant data were extracted from the National Health and Nutrition Examination Survey (NHANES 2011-2020), and the level of five metals in blood detected by inductively coupled plasma mass spectrometry was considered as exposures, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se). The correlations between individual metal and metal mixtures and CKD were then evaluated by survey-multivariable logistic regression (SMLR), generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Altogether, our study included 12,412 participants representing 572.6 million non-institutionalized US adults. Several single metals with the high quartile of exposure showed a positive association with the CKD ratio including Cd [(AOR = 1.873, 95% CI: 1.537, 2.284), Q4], Pb [(AOR = 1.559, 95% CI: 1.295, 1.880), Q4], and total Hg [(AOR = 1.169, 95% CI: 1.018, 1.343), Q2], while Mn [(AOR = 0.796, 95% CI: 0.684, 0.927), Q2] and Se [(AOR = 0.805, 95% CI: 0.664, 0.976), Q4] were negatively associated with the CKD ratio. In light of the positive fit of the WQS regression model, a significantly positive correlation was found between mixed metals and CKD (AOR = 1.373, 95% CI: 1.224, 1.539) after full covariate adjustment, and a similar finding was also detected in the BKMR model. Our study revealed that each single metal including Cd, Pb, and total Hg might have a positive association with CKD while this association was negative for both Mn and Se. The five metals might have a positive joint effect on CKD.

Joint effect of whole blood metals exposure with dyslipidemia in representative US adults in NHANES 2011-2020.

With little knowledge on the joint effects of metal exposure on dyslipidemia, we aimed to investigate the relationship between exposure to metal and dyslipidemia among US adults based on the National Health and Nutrition Examination Survey (NHANES). Based on the five NHANES waves (2011-2020), we selected five metals in blood as exposure, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se), which were detected by inductively coupled plasma mass spectrometry. Survey-multivariable logistic regression, generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR) were performed to determine whether dyslipidemia was associated with single metals or mixed metals. Our study included 12,526 participants aged from 20 to 80, representing 577.1 million non-institutionalized US adults. We found a positive association between several metals including Pb [adjusted odds ratio (AOR) = 1.332, 95%CI: 1.165, 1.522], total Hg (AOR = 1.264, 95%CI: 1.120, 1.427), Mn (AOR = 1.181, 95%CI: 1.046, 1.334), and Se (AOR = 1.771, 95%CI: 1.576, 1.992) and dyslipidemia. According to the WQS approach, metal mixtures were positively associated with dyslipidemia (AOR: 1.310, 95%CI: 1.216, 1.411) after a full-model adjustment. As is shown in the BKMR model, mixed metals tended to be positively associated with dyslipidemia ratios in a significant manner. Females, non-Hispanic White populations, people aged over 60, and those who did a little physical activity had a greater risk for dyslipidemia. Our findings suggest metals including Cd, Pb, Hg, Mn, and Se and their combinations may adversely affect dyslipidemia among US adults. Due to the cross-sectional nature of the study, it is possible that reverse causation may exist.

Sanguisorba officinalis L. promotes diabetic wound healing in rats through inflammation response mediated by macrophage.

Sanguisorba officinalis L., a traditional Chinese medicine, is frequently used to treat burns and scalds. But even so, it is unknown whether S. officinalis L. can accelerate diabetic wounds (DW) healing. Here, to bridge the gap, we employed in vivo and in vitro evaluations to assess the positive effect of S. officinalis L. ethanol extract (ESO) on DW. Results demonstrated that ESO dramatically improved the DW healing rate. With ESO treatment, the inappropriately elevated levels of IL6, IL1ß and TNFα in DW were reduced, while the expression of IL10 was increased, indicating that the abnormal inflammation in DW was also under control. Moreover, the abnormally elevated expression of CD86 was significantly inhibited and the expression of CD206 was significantly up-regulated following treatment with ESO. The global level of NF-κB protein was not affected by ESO treatment, but it suppressed the expression of phosphorylated NF-κB and prevented its nuclear entry. In addition, in RAW264.7 cells activated with lipopolysaccharide (LPS), the expression of NLRP3, Caspase1 and IL1ß were significantly diminished following ESO treatment. In conclusion, ESO was proved to be a promising treatment for DW healing due to its potential to accelerate the healing process by suppressing the inflammatory response. This was achieved by increasing the ratio of M2 to M1 polarization through blocking the NF-κB/NLRP3 signaling pathway.

Association of ambient PM1 exposure with maternal blood pressure and hypertensive disorders of pregnancy in China.

Evidence concerning PM1 exposure, maternal blood pressure (BP), and hypertensive disorders of pregnancy (HDP) is sparse. We evaluated the associations using 105,063 participants from a nationwide cohort. PM1 concentrations were evaluated using generalized additive model. BP was measured according to the American Heart Association recommendations. Generalized linear mixed models were used to assess the PM1-BP/HDP associations. Each 10 µg/m3 higher first-trimester PM1 was significantly associated with 1.696 mmHg and 1.056 mmHg higher first-trimester SBP and DBP, and with 11.4% higher odds for HDP, respectively. The above associations were stronger among older participants (> 35 years) or those educated longer than 17 years or those with higher household annual income (> 400,000 CNY). To conclude, first-trimester PM1 were positively associated with BP/HDP, which may be modified by maternal age, education level, and household annual income. Further research is warranted to provide more information for both health management of HDP and environmental policies enactment.

Analysis of the Efficacy of Multidrug Combination Chemotherapy Regimens for Osteosarcoma and the Management of Chemotherapeutic Reactions.

Purpose: To analyse the efficacy of high-dose methotrexate + adriamycin + cisplatin (HD-MTX + ADR + PDD, MAP) regimens applied to osteosarcoma and the pretreatment and resolution of chemotherapeutic reactions. Methods: The clinical data of 21 patients with osteosarcoma in our hospital from January 2015 to January 2018 were retrospectively analysed. All patients were treated with the MAP protocol, 21 days for 1 cycle, and treated with artificial joint replacement or amputation after 3∼4 cycles of treatment. The tumour tissue necrosis rate, limb preservation success rate after treatment, and chemotherapy response during chemotherapy were counted and analysed for all patients. A local recurrence rate, a distant metastasis rate, and an overall survival rate were recorded during the 3-year follow-up period. Results: After treatment, the percentage of tumour tissue necrosis ≥90% was 85.71% (18/21) and the percentage of successful limb preservation was 57.14% (12/21) in 21 patients with osteosarcoma. During chemotherapy, all 21 patients with osteosarcoma experienced various degrees of chemotherapy reactions, mainly bone marrow suppression of 100% (21/21), gastrointestinal reactions of 100% (21/21), liver function impairment of 66.67% (14/21), and cardiotoxicity of 52.38% (11/21), all of which improved and completed treatment after treatment. During the 3-year follow-up period, the 21 patients with osteosarcoma had a local recurrence rate of 9.52% (2/21), a distant metastasis rate of 28.57% (6/21), and an overall survival rate of 80.95% (17/21). Conclusion: With stringent protection and relief measures, patients with osteosarcoma treated with the MAP regimen have promising near-term outcomes, with high survival rates over 3 years and tolerable chemotherapy responses. The clinical trial is registered under L2015093.