Visualization of nasal powder distribution using biomimetic human nasal cavity model

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Possible mechanisms of toxic effects of per-and polyfluoroalkyl substances exposure on thyroid / 环境与职业医学

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants (POPs). They are widely used in food packaging, tableware coating, stain resistant furniture, and other industrial production. Humans are exposed to PFASs on a daily basis through drinking water and intaking food, use of consumer products containing PFASs, and occupational exposure during the production of PFASs or related products. A growing body of toxicological studies has shown that PFASs exposure disrupts the thyroid hormone (TH) system and causes hypothyroidism, which is further supported by population epidemiological studies. PFASs can damage thyroid follicular cells and sodium/iodine transporters to impair iodine uptake by thyroid cells. They interfere with the synthesis of thyroglobulin, reduce the activity of thyroid peroxidase, and affect the synthesis and secretion of TH. They interfere with TH transportation and biological effects via TH competitive binding thyroid transporter or thyroid hormone receptor. They suppress TH signaling pathway and deiodinase activity, interfere negative feedback mechanism, and accelerate TH metabolism and excretion. The processes of TH synthesis, transport, degradation, and biological effects may all be affected by PFASs exposure. This paper described possible toxic mechanisms of PFASs on the thyroid from four aspects: TH biosynthesis, transport, action on target cells, and metabolic excretion stage, and summarized the thyroid toxicity associated with PFASs exposure.

3D reconstruction assisted preoperative optimal design of anterolateral abdomen cross-region free perforator flap for repair of soft tissue defects in limbs / 中华显微外科杂志

Objective:To investigate the clinical effect of a 3D reconstruction assisted preoperative optimal design of anterolateral abdomen cross-region free perforator flaps for repair of soft tissue defects of limbs.Methods:Twenty patients who were treated for soft tissue defects of hand, forearm, foot and ankle in the Department of Hand Surgery, the Sixth Hospital of Ningbo from October 2017 to January 2020 were included in this study. Among the patients,17 had soft tissue defects in hand and forearm and 3 with composite tissue defects including ankle and soft tissue defect of foot. The sizes of soft tissue defects in limbs ranged from 6 cm × 8 cm - 36 cm × 18 cm. Twenty free cross-area perforator flaps were optimal designed with CTA and 3D assisted reconstruction before surgery. Following combinations of flaps were designed: (1) Free perforator flap with inferior abdominal artery and superior abdominal artery; (2) Free perforator flap with superficial iliac circumflex artery and deep iliac circumflex artery; (3) Free perforator flap with superficial iliac circumflex artery and inferior abdominal wall perforator artery; (4) Free perforator flap with perforators of superficial iliac circumflex artery plus superficial abdominal artery; (5) Free perforator flap with perforating artery of lower abdominal wall and superficial artery of abdominal wall. The overall nutritional area of a combined flap were 272.3 cm 2± 12.5 cm 2, 107.4 cm 2± 9.3 cm 2, 193.6 cm 2± 24.2 cm 2, 155.2 cm 2± 20.1 cm 2 and 203.7 cm 2± 16.3 cm 2, respectively. All the donor sites were sutured directly in one stage. The appearance, texture, blood supply, colour, joint movement of affected limbs, recovery and function of donor sites were observed through postoperative follow-up visits at the outpatient clinic. Results:Among the 20 anterolateral transventral perforator flaps, 18 flaps survived successfully; One had partial necrosis after surgery, and healed after dressing change. Subcutaneous haematoma occurred in 1 flap, and survived after drainage. In this study, there was no postoperative infection of flap. A total of 19 flaps healed in one stage, except 1 that had a delayed healing and the flap wound was closed after dressing change for 1 week. According to Disability of Arm, Shouder and Hand (DASH) questionnaire evaluation, which is widely used in the world to evaluate the therapeutic effect after limb injury, combined with the 6-12 months of follow-up, the functional recovery of 17 patients with upper limbs iniury was 7 in excellent, 9 in good and 1 in poor. The overall excellent and good rate achieved 94.1%. All the 3 patients with foot injury recovered well, and the walking and jumping were not significantly affected. The results were all excellent according to the Maryland Foot Function Scoring. Sensation of flaps was evaluated according to the British Sensory Function Evaluation, it showed: 3 in S 2, 15 in S 3 and 2 in S 3+. All 20 flaps had good blood supply, in soft texture, good colour, feeling, thickness and movement. The donor sites all healed well. Conclusion:Combined with an optimal preoperative design, the perforator flap of anterior lateral wall cross-region can obtain a satisfactory clinical efficacy in repair of large area soft tissue defects. It is a feasible treatment method.

A cross-sectional study of iodine nutrition status in pregnant women in Zhejiang Province in 2021 / 中华地方病学杂志

Objective:To evaluate the current situation of prevention and control of iodine deficiency disorders (IDD), and to describe the iodine nutrition level of pregnant women in key population in Zhejiang Province.Methods:In 2021, a cross-sectional survey on iodine nutrition status of the population was conducted in all 90 counties (cities, districts) in Zhejiang Province. Each county (city, district) was divided into five districts: east, west, south, north, and central. One township (street) was selected from each district, and 20 pregnant women were selected from each township (street) to collect edible salt samples and one random urine sample for salt and urinary iodine testing. The above indicators were stratified and analyzed according to urban, rural, coastal, inland, early pregnancy, mid pregnancy, and late pregnancy.Results:A total of 9 679 pregnant women's salt samples were tested, with a salt iodine content of (20.2 ± 9.2) mg/kg, an iodized salt coverage rate of 84.2% (8 153/9 679), and a qualified iodized salt consumption rate of 80.4% (7 785/9 679). Among them, the qualified iodized salt consumption rate of pregnant women in coastal areas was 69.4% (3 175/4 575), significantly lower than that in inland areas [90.3% (4 610/5 104)]; and the proportion of non iodized salt consumption in coastal areas [25.8% (1 181/4 575)] was significantly higher than inland areas [6.8% (345/5 104)]. A total of 9 679 pregnant women's urine samples were tested, with a median urinary iodine of 133.0 μg/L ( < 150 μg/L). In urban areas, the median urinary iodine (129.8 μg/L) was lower than that in rural areas (135.0 μg/L). Likewise, the median urinary iodine was 126.0 μg/L, lower than inland areas (140.3 μg/L). And as pregnancy progressed, the iodine nutrition level of pregnant women gradually decreased (the median urinary iodine: 137.0 μg/L in early pregnancy, 134.1 μg/L in mid pregnancy, and 129.4 μg/L in late pregnancy).Conclusion:In 2021, pregnant women in Zhejiang Province are in a state of iodine deficiency, and there is a greater risk in urban areas compared to rural areas and coastal areas compared to inland areas.

Research on advances of the evaluation indexes for individual iodine nutrition / 中华地方病学杂志

At present, Chinese residents have three iodine nutritional states: iodine deficiency, iodine appropriate and iodine excess. Appropriate iodine nutrition is crucial to the growth, development, and metabolic regulation of the body. Accurate assessment of individual iodine nutrition level is helpful to accurately understand the iodine status of the body and prevent iodine deficiency or excess. Previous indexes for assessing iodine nutrition include urinary iodine, thyroid stimulating hormone, goiter rate and so on, but these indexes have different degrees of shortcomings in individual iodine nutrition evaluation. This paper reviews the commonly used individual iodine nutrition evaluation indexes, and discusses the possibility of combined application of multiple indexes.

Prognosis Analysis of Early-stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiotherapy / 中国肺癌杂志

BACKGROUND@#With the aging of the population and the increased importance of lung cancer screening, the number of early-stage lung cancer patients has been on the rise in recent years, which can be classified into operable early-stage lung cancer and inoperable early-stage lung cancer. The most common pathological type is non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is the optimal treatment for inoperable early-stage NSCLC. The aim of this study was to investigate the prognosis of early-stage NSCLC patients treated with SBRT and its influencing factors in order to reduce the side effects of radiotherapy and improve the survival and quality of life.@*METHODS@#Clinical data and follow-up outcomes of early-stage NSCLC patients treated with SBRT in our hospital from August 2010 to August 2020 were collected. Kaplan-Meier method was used to assess the prognosis, and the Cox proportional risk model was used for multivariate prognostic analysis.@*RESULTS@#A total of 165 patients were included with a median follow-up time of 43.2 (range: 4.8-132.1) mon. The local control (LC) rates at 1-yr, 2-yr and 5-yr were 98.1%, 94.8% and 86.5% respectively. Karnofsky performance status (KPS) score greater than 80 was an independent prognostic factor for LC (P=0.02). The overall survival (OS) rates at 1-yr, 2-yr and 5-yr were 97.6%, 93.0% and 68.9% respectively. A biological equivalent dose when α/β=10 (BED10) greater than 132 Gy was an independent prognostic factor for OS (P=0.04). Progression-free survival (PFS) rates at 1-yr, 2-yr and 5-yr were 93.3%, 79.5% and 55.3% respectively. The distance metastasis free survival (DMFS) rates at 1-yr, 2-yr and 5-yr were 94.5%, 83.2% and 58.4% respectively. BED10 greater than 150 Gy was an independent prognostic factor for DMFS (P=0.02). The regional control (RC) rates at 1-yr, 2-yr and 5-yr were 98.8%, 95.4% and 87.9% respectively.@*CONCLUSIONS@#SBRT is effective in treating early-stage NSCLC. KPS greater than 80 is an independent prognostic factor for LC; BED10 greater than 132 Gy is an independent prognostic factor for OS; BED10 greater than 150 Gy is an independent prognostic factor for DMFS.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Effects of intravenous treprostinil in high-risk patients after total cavo-pulmonary connection / 中国胸心血管外科临床杂志

@#Objective     To explore the effects of intravenous treprostinil in different doses on the hemodynamics and postoperative outcomes after high-risk total cavo-pulmonary connection (TCPC). Methods    From 2018 to 2021, among 189 patients who underwent TCPC in the Department of Pediatric Cardiac Surgery of Fuwai Hospital, 26 high-risk patients who received the intravenous treprostinil therapy were retrospectively analyzed. There were 12 males and 14 females, with an age of 4 (3, 6) years and a weight of 17.6±6.2 kg. The patients were divided into two groups: a high-dose group [15 patients, maintaining dose>10 ng/(kg·min)] and a low-dose group [11 patients, maintaining dose≤ 10 ng/(kg·min)]. The hemodynamics before treprostinil using and during the first 24 hours after reaching the maintaining dose of treprostinil, and postoperative outcomes of the two groups were investigated. Results    The incidence of heterotaxia was higher in the high-dose group (66.7% vs. 18.2%, P=0.021). During the observation period, the mean pulmonary artery pressure decreased from 11.9±3.6 mm Hg to 11.0±3.3 mm Hg in the low-dose group (P=0.013), and from 12.9±4.7 mm Hg to 10.2±3.4 mm Hg in the high-dose group (P=0.001). The decreasing effect in the high-dose group was better than that in the low-dose group (P=0.010). There was no statistical difference in the postoperative outcomes between the two groups (P>0.05). In terms of side effects, patients needed temporarily increased dosage of vasoactive drugs to maintain stable blood pressure during 6-12 h after treprostinil therapy in the high-dose group. Conclusion    In patients after high-risk TCPC, intravenous high-dose treprostinil has a better therapeutic effect on reducing pulmonary artery pressure. However, it should be noted that increased dosage of vasoactive agents may be required to maintain blood pressure stability in patients with high-dose treprostinil.

CRYAB reduces cigarette smoke-induced inflammation, apoptosis, and oxidative stress by retarding PI3K/Akt and NF-kB signaling pathways in human bronchial epithelial cells

Background: Chronic obstructive pulmonary disease (COPD) is a familiar airway disease characterized by chronic immune response in the lungs. More and more evidences have assured that cigarette smoking is the primary reason for the progression of COPD, but its related regulatory mechanism requires further clarification. The α-B-crystallin (CRYAB) has been identified to exhibit vital functions in different diseases, and is down-regulated in the alveoli of mice mediated by cigarette smoke extract (CSE).Methods: The messenger RNA expression of CRYAB was assessed by reverse transcription--quantitative polymerase chain reaction. The proteins’ expressions were tested using Western blot method. The cytotoxicity was measured by lactate dehydrogenase assay. The levels of malondialdehyde, superoxide dismutase, catalase, myeloperoxidase, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were assessed through enzyme-linked-immunosorbent serologic assay (ELISA).Results: In this study, it was discovered that the expression of CRYAB was markedly decreased with the increased time of cigarette smoking. Moreover, CRYAB overexpression increased cell viability and decreased cell apoptosis induced by cigarette smoke. In addition, the strengthened oxidative stress and inflammation mediated by CSE treatment was relieved after overexpression of CRYAB. Eventually, results OF Western blot method confirmed that CRYAB retarded the activation of phosphatidylinositol 3-kinase–Ak strain transforming (PI3K–Akt) and nuclear factor kappa B (NF-κB) signaling pathways.Conclusion: Our results manifested that CRYAB reduced cigarette smoke-induced inflammation, apoptosis, and oxidative stress in normal and diseased bronchial epithelial (NHBE) and human bronchial epithelial (BEAS-2B) cells by suppressing PI3K/Akt and NF-κB signaling pathways, which highlighted the functioning of CRYAB in preventing or treating COPD (AU)

Impact of Vaccination, Prior Infection, and Therapy on Delta and Omicron Variants

We studied 249,070 patients who were tested for SARS-CoV-2 in the Cleveland Clinic Health System between October 1, 2021 and January 31, 2022. We found that vaccination, especially with recent boosting, was more effective than prior infection and monoclonal antibody therapy against both the delta and omicron variants. Vaccination and prior infection were much less effective against infection with the omicron variant than with the delta variant, but the opposite was true of death after infection. Boosting greatly increased the effectiveness of the two mRNA vaccines against both infection and death, although its effects waned markedly after 6 months. In addition, monoclonal antibody therapy was notably less effective at preventing death from the omicron variant than from the delta variant. Finally, the relatively low mortality of the omicron variant was due to both the reduced lethality of this variant and the increased population immunity acquired from booster vaccination and previous infection.

Comparison of random forests and SARIMA in Predicting Brucellosis Incidence / 公共卫生与预防医学

Objective To compare the effects of random forest and SARIMA (Seasonal Autoregressive Integrated Moving Average) on predicting incidence rate of brucellosis. Methods Using Brucellosis cases reported in the China Disease Prevention and Control Information System from 2005 to 2017, two models, random forest and SARIMA, were established for training and forecasting, and the forecasting results of the two models were compared. Results The R2 (R Squared) and RMSE (Root Mean Squared Error) of SARIMA model and random forest model are 0.904, 0.034351, 0.927 and 0.03345 respectively. Conclusion Both models have high prediction accuracy and can predict the incidence of brucellosis. Random forest prediction is a little bit better than SARIMA model and has more practical value.

Evaluation of soil environmental quality of cultivated land in the Donghe River Basin of Chenzhou City, Hunan Province by three methods / 环境与职业医学

Background Heavy metal pollution in cultivated land will affect crop yield and quality, as well as groundwater quality, ecological security, and human health. Objective To analyze the pollution status of heavy metal elements such as chromium (Cr), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), and lead (Pb) in cultivated soils of the Donghe River Basin in Chenzhou City, and to evaluate the environmental quality of local cultivated soil. Methods A total of 16 samples of cultivated soil from the Donghe River Basin in Chenzhou City were collected, and the contents of Cr, Cu, Zn, As, Cd, and Pb in the samples were determined by inductively coupled plasma mass spectrometry. The Nemerow comprehensive pollution index method (the evaluation indicators included both Nemerow comprehensive pollution index and single pollution index), the geological accumulation index method, and the potential ecological risk index method were used to evaluate the soil environmental quality. Results The average levels of Cr, Cu, Zn, As, Cd, and Pb in the soil samples in the study area were 58.25, 49.50, 273.88, 137.76, 2.92, and 672.29 mg·kg−1, respectively. The average values of Cu, Zn, As, Cd, and Pb were all exceeded the background values of soil elements in Hunan Province. The single pollution indices of As, Cd, Pb, and Zn in soil were 4.40, 9.74, 5.85, and 1.15 respectively. The contamination of As and Pb reached 93.75% and 81.25% respectively. The geological accumulation indices of soil As, Cd, Pb, and Zn were 2.11, 3.71, 2.97, and 0.58, respectively, which showed heavy Cd pollution, moderate As and Pb pollution, and slight Zn pollution. The potential ecological hazard indices of soil Cr, Cu, Zn, As, Pb, and Cd were 1.63, 9.07, 2.90, 87.75, 113.18, and 695.76. 81.Twenty five percent of Cd samples showed heavy pollution and above, and 62.50% of Pb samples had moderate pollution and above. The Nemerow comprehensive pollution index was 7.72, which belonged to heavy pollution; and the comprehensive potential ecological risk index was 910.29, which belonged to high ecological risk. Conclusion There are certain differences in the results of different evaluation methods. The cultivated soils of the Donghe River Basin in Chenzhou City, is seriously polluted by heavy metals, and Cd, As, and Pb are the main polluting elements.

Epidemiological and clinical features of 62 patients with visceral leishmaniasis / 中华传染病杂志

Objective:To analyze the epidemiological and clinical features of patients with visceral leishmaniasis (VL), and to improve the understanding of the disease and standardize the diagnosis and treatment.Methods:The clinical data and diagnosis and treatment process of 62 patients with VL admitted to The First Hospital of Lanzhou University from January 2010 to December 2020 were retrospectively analyzed. The clinical symptoms and laboratory data, including aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and procalcitonin (PCT) were compared between children and adults. Chi-square test was used for statistical analysis.Results:Of the 62 patients, 31(50.0%) patients were males, 38(61.3%) patients were children and 24(38.7%) were adults. There were 32 cases (51.6%) living in Longnan City, and 11 cases (17.7%) living in Gannan Tibetan Autonomous Prefecture. Forty-seven cases (75.8%) had a delay over 30 days from onset to diagnosis. All patients had fever and chills, 34 cases (54.8%) had fatigue and poor appetite, 30(48.4%) had cough and expectoration, 10 cases (16.1%) had headache and dizziness, 45 cases (72.6%) had splenomegaly, 40 cases (64.5%) had anemia, and 29 cases (46.8%) had hepatomegaly. There were 32 cases (51.6%) accompanied with respiratory infection, 11 cases (17.7%) accompanied with hemophagocytic lymphohistiocytosis and 10 cases (16.1%) accompanied with abnormal liver function. Of the 60 patients who received treatment, 14 were recurrent cases who had received at least one course of pentavalent antimony monotherapy before admission. Forty-six patients received standard antimony monotherapy, 14 patients received standard antimony combined with amphotericin B therapy. Thirteen patients discontinued amphotericin B due to impaired renal function, and 50 patients were followed up for half a year without recurrence. The proportions of splenomegaly and hepatomegaly in children were 86.8%(33/38) and 65.8%(25/38), respectively, and the corresponding numbers in adults were 50.0%(12/24) and 16.7%(4/24), respectively. The differences were statistically significant ( χ2=10.03 and 14.26, respectively, both P<0.050). Thirty-three cases (86.8%) in children and 14 cases (58.3%) in adults had a delay over 30 days from onset to diagnosis. The difference was statistically significant ( χ2=6.52, P=0.011). The proportions of patients who had elevated AST, LDH and PCT were 76.3%(29/38), 94.3%(33/35) and 73.9%(17/23) in children, respectively, while 45.8%(11/24), 71.4%(15/21) and 5/17 in adults, respectively, and the differences were all statistically significant ( χ2=5.97, 3.89 and 7.82, respectively, all P<0.050). Conclusions:Patients with VL are tend to have complications and be severe. Early diagnosis and standardized treatment are important measures to improve the prognosis. Patients who have failed antimony treatment can be treated with amphotericin B or combination therapy, but kidney injury and other adverse reactions should be closely monitored.

Research progress on immune checkpoint inhibitors combined with stereotactic ablative body radiotherapy for advanced non-small cell lung cancer / 中华放射肿瘤学杂志

The effect of radiotherapy on anti-tumor immunity is bidirectional, immunotherapy, especially the combination of immune checkpoint inhibitors (ICIs) and radiotherapy, can produce synergistic effects on anti-tumor immunity. Compared with conventional radiotherapy, stereotactic ablative body radiotherapy (SABR) can achieve high-precision and high-dose irradiation on target lesions, and has stronger anti-tumor immune activation effect. At the same time, due to the steep dose gradient, SABR can better protect the surrounding normal tissues, which is an effective means for the rapid control of local lesions in advanced non-small cell lung cancer (NSCLC). ICIs are an important component of standard treatment for advanced NSCLC. There is growing evidence that SABR in combination with ICIs can benefit patients with advanced NSCLC. This article reviews the biological basis and clinical research progress on the combination of these two therapies, aiming to provide reference for the domestic counterparts to better use this new treatment model.

Analysis of causes and countermeasures against marine organisms blocking event at cold source intake of coastal nuclear power plant / 中华放射医学与防护杂志

The cold source system of a nuclear power plant, as important part of a nuclear power project, is of great significance to guarantee the safe operation of a nuclear power plant. In recent years, there have been some cases of marine organism blockage at cold source intake at coastal nuclear power plants in China, which has adversely affected the safety and economy of nuclear power plants. According to the research result of cold source safety in coastal nuclear power plants in China and in compliance with the requirements of nuclear safety regulatory control and the engineering practice experience, the causes of, and countermeasures against, marine organism blockage at cold source intake are analyzed to further improve the safety and economy of nuclear power plants.

Exposure to and health effects of bisphenols: a review / 预防医学

Abstract@#Bisphenols (BPs), which are mainly used in the production of polycarbonates and epoxy resins, are common endocrine disruptors (EDCs) in natural environments. Human mainly exposes to BPs via ingestion and skin. Previous studies have deteted BPs in human urine, serum, and milk samples, and children and pregnant women have a high level of exposure to to BPs. Based on international and national publications pertaining to BPs since 2009, this review describes the exposure to BPs in human urine, serum, and milk and summarizes neuroendocrine dysfunctions, oxidative stress injury and epigenetics changes caused by BPs, so as to provide insights into reducing the exposure to and health risk of BPs.

Iodine nutrition and goiter prevalence among children at ages of 8 to 10 years in Zhejiang Province / 预防医学

Objective@#To investigate the status of iodine nutrition and prevalence of goiter among children at ages of 8 to 10 years in Zhejiang Province in 2021, so as to provide insights into the management of iodine deficiency in children.@*Methods @#A total of 90 counties (districts) were sampled as field survey sites from 11 cities of Zhejiang Province using a multi-stage stratified random sampling method in 2021, and non-residential children at ages of 8 to 10 years in these sites were sampled as study subjects. Subjects' household edible salt samples and random urine samples were collected. The iodine content in salt and urinary iodine level were determined using the direct titration method and arsenic-cerium catalytic spectrophotometry for evaluation of iodine nutrition among children. In addition, the lateral lobe of the thyroid gland was measured using ultrasound, and the prevalence of goiter was estimated. @*Results@#A total of 19 363 children were recruited, including 9 710 male children and 9 653 female children, with a male to female ratio of 1.01︰1, and there were 10 704 urban children (55.28%) and 8 659 rural children (44.72%), 9 149 children living in coastal areas (47.25%) and 10 214 children in inland regions (52.75%). The mean iodine content was (19.79±9.25) mg/kg in salt, and the coverage of qualified iodized salt (15 252) was 78.77%. The coverage of qualified iodized salt was significantly lower in urban children than in rural children (76.70% vs. 81.21%; χ2=68.301, P<0.001), and was lower in children living in coastal regions than in inland regions (68.05% vs. 88.27%; χ2=1 270.769, P<0.001). The median urinary iodine concentration was 195.1 μg/L, and the household iodine content in salt correlated positively with urinary iodine concentration in children (rs=0.383, P<0.001). There were 2 885 children with iodine deficiency (14.90%), 7 137 children with adequate iodine (36.86%), 5 414 children with excessive iodine intake (27.96%), and 3 927 children with iodine overdose (20.28%), and the distribution of iodine nutrition in children varied significantly in regions (χ2=283.277, P<0.001) and gender (χ2=126.349, P<0.001). The prevalence of goiter was 2.45% among 7 195 children receiving ultrasound examinations, and a higher prevalence rate of goiter was detected in urban children than in rural children (2.76% vs. 2.00%; χ2=3.962, P=0.047). @*Conclusions @#The overall urinary iodine nutrition was adequate among children at ages of 8 to 10 years in Zhejiang Province in 2021, and the prevalence of goiter in children fell within the threshold defined in the criteria of elimination of iodine deficiency. However, the supervision of the iodized salt quality remains to be improved and iodine deficiency control remains to be reinforced.

Research progress on ecotoxicological effects of antidepressants / 预防医学

Abstract：@#With the increasing rise in antidepressant consumption, more and more antidepressants and their metabolic products enter into water and soil environments. This will cause toxicity to animals living in these environments, and antidepressants may be transferred to humans via food chain, leading to human health risks. Based on national and international publications pertaining to environmental pollution and toxic effects of antidepressants during the period between 2005 and 2021, this review summarizes the biological accumulation, acute toxicity, reproductive and developmental toxicity, metabolic effects and biological behavior changes of antidepressants, so as to provide insights into the elucidation of the impact of antidepressants on human health risks.

A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation

SummaryWhile SARS-CoV-2 likely has animal origins1, the viral genetic changes necessary to adapt this animal-derived ancestral virus to humans are largely unknown, mostly due to low levels of sequence polymorphism and the notorious difficulties in experimental manipulations of coronavirus genomes. We scanned more than 182,000 SARS-CoV-2 genomes for selective sweep signatures and found that a distinct footprint of positive selection is located around a non-synonymous change (A1114G; T372A) within the Receptor-Binding Domain of the Spike protein, which likely played a critical role in overcoming species barriers and accomplishing interspecies transmission from animals to humans. Structural analysis indicated that the substitution of threonine with an alanine in SARS-CoV-2 concomitantly removes a predicted glycosylation site at N370, resulting in more favorable binding predictions to human ACE2, the cellular receptor. Using a novel bacteria-free cloning system for manipulating RNA virus genomes, we experimentally validated that this SARS-CoV-2-unique substitution significantly increases replication in human cells relative to its putative ancestral variant. Notably, this mutations impact on virus replication in human cells was much greater than that of the Spike D614G mutant, which has been widely reported to have been selected for during human-to-human transmission2,3.

Cell-free DNA barcode-enabled single-molecule test for non-invasive prenatal diagnosis of phenylketonuria: an analysis of four cases / 中华围产医学杂志

Objective:To analyze the applicability and feasibility of a cell-free DNA barcode-enabled single-molecule test (cfBEST) in non-invasive prenatal diagnosis of phenylketonuria.Methods:This study recruited four pregnant women who were prenatally diagnosed as heterozygous carriers of hot spot mutations in the PAH gene from pedigrees with phenylketonuria at the First Affiliated Hospital of Zhengzhou University from July to September 2019. The frequency of mutations in maternal plasma cell-free DNA and the fetuses' genotypes were analyzed by cfBEST. Nested polymerase chain reaction primers were designed to amplify the mutation sites in each pedigree. The results of cfBEST were compared with those of invasive prenatal diagnosis. Descriptive analysis was used for data analysis. Results:In pedigree 1, the frequency of c.603T>G and c.842+2T>A mutations in maternal plasma cell-free DNA were 48.40% (291/601) and 9.70% (61/628), which was detected by cfBEST. The fetus was diagnosed with phenylketonuria with two heterozygous mutations. In pedigree 2, the frequency of c.1238G>C and c.842+2T>A mutations in maternal plasma cell-free DNA was 43.70% (786/1 798) and 0% (0/1 550), respectively. Both mutations were wild-type, and the fetus was neither phenylketonuria nor a carrier. In pedigree 3, the frequency of c.1045T>G and c.728G>A mutations in maternal plasma cell-free DNA was 44.00% (930/2 112) and 0% (0/705), respectively, suggesting that both mutations in the fetus were wild-type, and the fetus was neither phenylketonuria nor a carrier. In pedigree 4, the frequency of c.755G>A and c.728G>A mutations were 45.40% (743/1 637) and 4.50% (28/849), respectively, which indicated that the former was wild-type, and the latter was heterozygous; namely the fetus was a carrier of phenylketonuria. The results of cfBEST were consistent with those of invasive prenatal diagnosis. Three pedigrees (Pedigree 2, 3 and 4) continued the pregnancy to full-term, and the phenylalanine levels in the neonates were all below 120 μmol/L. No abnormalities were reported in those three infants during follow-ups at one, three, and six months after birth.Conclusions:The cfBEST could be used for non-invasive prenatal diagnosis of phenylketonuria caused by PAH gene mutation, but further studies with a larger sample size are needed.