A Prediction Model for the Efficacy of Transvaginal Repair in Patients With Cesarean Scar Defect: An Evidence-Based Proposal for Patient Selection.

STUDY OBJECTIVE: To establish a prediction model to help doctors determine which patients with cesarean scar defect are more suitable for transvaginal repair. DESIGN: Retrospective analysis. SETTING: Xinhua Hospital and Shanghai First Maternity & Infant Hospital between June 2014 and May 2021. PATIENTS: 1015 women who underwent transvaginal repair of cesarean scar defect (CSD). INTERVENTIONS: All enrolled patients underwent CSD repair performed by the same gynecologist and his team. And followed up a clinic visit at 6 months to record their menstruation and measure multiple parameters of the CSD by Magnetic Resonance Imaging. MAIN OUTCOMES AND MEASURES: CSD patients are categorized as optimal healing group when the menstruation duration is no more than 7 days, meanwhile the thickness of residual myometrium is no less than 5.39 mm after vaginal repair. The final nomogram is constructed to predict surgical outcomes based on preoperative variables. RESULTS: The key factors that determine optimal healing are the timing of cesarean section (elective or emergency), menstrual cycle, CSD length, width, depth, and the thickness of the lower uterine segment. With the prediction model, scores are given to each parameter according to the statistics. Total scores range from 0 to 25 points, with a cutoff point of 16.5. When a score is greater than 16.5, the transvaginal repair can achieve optimal healing. Uterine position (anteflexion or retroflexion) and preoperative thickness of residual myometrium are the key factors affecting postoperative thickness of residual myometrium. The width of the CSD and the thickness of the lower uterine segment are the key factors affecting abnormal uterine bleeding symptoms (p < 0.01). CONCLUSIONS: For the first time, we established a prediction model system that may predict the repair effect of CSD and can potentially be useful in future clinical trials to determine which patients are more suitable for surgery or other treatment options.

Outcomes of vaginal repair and vaginal repair combined with GnRHa administration in the treatment of cesarean section scar defects: A randomized clinical trial.

STUDY OBJECTIVE: To prospectively investigate whether the application of vaginal repair (VR) of cesarean section scar defect (CSD) combined with a gonadotropin-releasing hormone agonist (GnRHa) achieve better clinical outcomes than VR alone. DESIGN: A randomized clinical trial. SETTING: University hospital. PATIENTS: A total of 124 women with CSD were undergoing expectant management from December 2016 to September 2021. 61 were randomised to VR+ GnRHa and 63 to VR alone. INTERVENTION: Vaginal repair combined with GnRHa and vaginal repair alone. MEASURES AND MAIN RESULTS: The primary outcome was the duration of menstruation and thickness of the remaining muscular layer (TRM) at 6 months after surgery. Secondary outcomes included the length, width and depth of the CSD; operation time; estimated blood loss; hospitalization time; and operative complications. Women were treated with either VR (n = 63) or VR + GnRHa (n = 61). Menstruation and TRM in patients pre. vs. post comparisons either with VR or VR + GnRHa are significant improved (P < .05). Significant differences in menstruation duration and TRM occurred in patients treated with VR + GnRHa compared with those treated with VR (P < .05). Moreover, the rate of CSD after surgery in the VR group was significantly higher than that in the VR + GnRHa group (P = .033), and CSD patients in the VR + GnRHa group achieved better therapeutic effects than those in the VR group (P = .017). Patients who received VR + GnRHa had a shorter menstruation duration and a greater increment of TRM postoperatively than did patients treated with VR alone (P = .021; P = .002, respectively). CONCLUSION: VR + GnRHa therapy has a greater potential to improve scar healing and reduce the number of menstruation days than VR alone for symptomatic women with CSD. PRéCIS: Vaginal Repair Combined with GnRHa Creates Better Therapeutic Effects of CSD. TRIAL REGISTRATION: Date of registration: October 13, 2016, Date of initial participant enrollment: December 20, 2016, Clinical trial identification number: NCT02932761, URL of the registration site: ClinicalTrials.gov, Figshare DOI: 10.6084/m9.figshare.24117114 LINK TO THE CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02932761.

Effects of food-borne cholesterol supplementation on lead-induced neurodevelopmental impairments of rats based on BDNF signaling pathway and cholesterol metabolism.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-ß levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

Decreased estimated glomerular filtration rate predicts long-term recurrence after catheter ablation of atrial fibrillation in mild to moderate renal insufficiency.

BACKGROUND: Catheter ablation is an established therapy for atrial fibrillation (AF), but recurrence after ablation remains a great challenge. Additionally, little is known about the effect of renal function on the efficiency of AF ablation. This study aimed to evaluate the predictors of the prognosis of catheter ablation for AF, especially the effect of renal function. METHODS: A total of 306 drug-refractory symptomatic patients with AF who underwent first-time catheter ablation were enrolled in the present study. Individuals underwent circumferential pulmonary vein isolation for paroxysmal AF and stepwise ablation for persistent AF. RESULTS: The follow-up time was 27.2 ± 19.5 months, 202 patients (66.01%) were free of atrial tachyarrhythmia (non-recurrence group), and the other 104 patients experienced recurrence (recurrence group). The recurrence group had a larger left atrial diameter (LAD) and left atrial volume (LAV), a higher LAV index (LAVI) (both, p < 0.01), and a lower estimated glomerular filtration rate (eGFR) (53.5 ± 14.4 vs. 65.5 ± 13.3 ml/min/1.732, p < 0.001) and creatinine clearance rate (CCr) (85.2 ± 26.1 vs. 101.5 ± 29.4 ml/min, p < 0.05). Multivariate logistic regression indicated both eGFR (p = 0.002) and LAVI (p < 0.001) as independent associated factors for long-term recurrence after single catheter ablation; multivariate Cox proportional hazard regression with backward feature selection identified both eGFR (HR: 0.93, 95% CI: 0.91-0.95, p < 0.001) and LAVI (HR: 1.32, 95% CI: 1.25-1.40, p < 0.001) as independent prognostic factors for recurrence when adjusting other clinical variables. CONCLUSIONS: Decreased eGFR and elevated LAVI may facilitate the long-term recurrence of atrial tachyarrhythmia after catheter ablation for AF.

Prognostic value of lymphovascular invasion in stage II colorectal cancer patients with an inadequate examination of lymph nodes.

BACKGROUND: Lymphovascular invasion (LVI) is defined as the presence of cancer cells in lymphatics or blood vessels. This study aimed to evaluate the prognostic value of LVI in stage II colorectal cancer (CRC) patients with inadequate examination of lymph nodes (ELNs) and further combined LVI with the TNM staging system to determine the predictive efficacy for CRC prognosis. Adjuvant chemotherapy (ACT) was then evaluated for stage II CRC patients with LVI positivity (LVI+). METHODS: In order to avoid the effects of different ACT regimens, among 409 stage II patients, we chose 121 patients who received FOLFOX regimen and the 144 patients who did not receive ACT as the object of study. LVI was examined by hematoxylin-eosin (HE) staining. Kaplan-Meier analysis followed by a log-rank test was used to analyze survival rates. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Harrell's concordance index (C-index) was used to evaluate the accuracy of different systems in predicting prognosis. RESULTS: The LVI+ status was significantly associated with pT stage, degree of differentiation, tumor stage, serum CEA and CA19-9 levels, perineural invasion (PNI), tumor budding (TB), and KRAS status. The 5-year overall survival (OS) rate of stage II patients with < 12 ELNs and LVI+ was less than stage IIIA. Multivariate analyses showed that LVI, pT-stage, serum CEA and CA19-9 levels, PNI, TB, and KRAS status were significant prognostic factors for stage II patients with < 12 ELNs. The 8th TNM staging system combined with LVI showed a higher C-index than the 8th TNM staging system alone (C-index, 0.895 vs. 0.833). Among patients with LVI+, the ACT group had a significantly higher 5-year OS and 5-year disease-free survival (DFS) than the surgery alone (SA) group (5-year OS, 66.7% vs. 40.9%, P = 0.004; 5-year DFS, 64.1% vs. 36.3%, P = 0.002). CONCLUSIONS: LVI is an independent prognostic risk factor for stage II CRC patients. Combining LVI with the 8th TNM staging system improved the predictive accuracy for CRC prognosis. ACT in stage II CRC patients with LVI+ is beneficial for survival.

Clinical value of detecting IQGAP3, B7-H4 and cyclooxygenase-2 in the diagnosis and prognostic evaluation of colorectal cancer.

BACKGROUND: The IQ-motif-containing GTPase-activating protein (IQGAP) family comprises three members, IQGAP1, IQGAP2 and IQGAP3. IQGAP3 is the latest addition to the family. This study mainly investigated the novel marker IQGAP3 at serum and tumor tissue levels compared with the markers B7-H4 and cyclooxygenase-2 (COX-2) in patients with colorectal cancer (CRC) and in healthy individuals, aiming to evaluate the diagnostic and prognostic value of IQGAP3 for CRC. MATERIALS AND METHODS: Serum samples were collected prior to any therapy in 118 CRC patients and as part of a routine examination in 85 healthy individuals. Serum IQGAP3, B7-H4 and COX-2 levels were measured using commercially available ELISA kits. Immunohistochemistry was performed to detect the IQGAP3, B7-H4 and COX-2 in tumor tissues and normal para-carcinoma tissues. The receiver operating characteristics (ROC) curve and the area under the curve (AUC) were used to evaluate and compare the diagnostic value of different serum tumor markers. Univariate and multivariate analyses were performed to identify the prognostic risk factors for CRC. RESULTS: IQGAP3, B7-H4 and COX-2 showed low or high expression in tumor tissues while no expression in normal para-carcinoma tissues. Serum levels of IQGAP3 in CRC group were significantly higher than those in healthy control group (P < 0.001). The IQGAP3 AUC was 0.799, while the B7-H4 AUC was 0.795 and the COX-2 AUC was 0.796. IQGAP3 seemed to be superior to B7-H4 and COX-2 in detecting CRC, with the highest sensitivity among the three markers. Multivariate analysis showed that T stage, N stage, differentiation degree, TNM stage and both serum and tissue IQGAP3, B7-H4 and COX-2 levels were significant prognostic factors for CRC. CONCLUSIONS: IQGAP3 has a better diagnostic efficacy than B7-H4 and COX-2 in detecting CRC and it has value in predicting the prognosis of patients with CRC.

The trend of lead poisoning rate in Chinese population aged 0-18 years old: a meta-analysis.

BACKGROUND: Childhood lead poisoning is a public health problem gained widely attention for the health damage caused by lead exposure. Pediatrics defines lead poisoning as BLL of or higher than 10 µg/dL, which leads to harmful effects in nervous system, hematological system and urinary system. This study investigates the percentage of 0-18 year old Chinese population with blood lead level (BLL) ≥10 µg/dL during 1990-2012 by searching epidemiologic studies from electronic database focused on BLL in mainland China. METHODS: Epidemiologic studies about BLL in China mainland between January 1990 and October 2012 were searched from electronic databases including CNKI, CBM disc, Wanfang Data, Pubmed and Medline. Data extraction, data analysis and risk of bias assessments were performed. RESULTS: Fifty-five articles were included in analysis containing 200,002 subjects, covering 19 provinces, autonomous regions and municipalities. The corrected pooled rate by trim and fill method under random effect model was 9 % (95 CI: 6 %, 12 %). The corrected pooled lead poisoning rate by trim and fill method was 28.1 % (95 % CI: 21.6 %, 34.6 %) from data published during 1990-2000, much higher than the rate during 2001-2005 (10.5 %, 95 % CI: 6.4 %, 14.5 %) and the rate during 2006-2012 (5.3 %, 95 % CI: 3.7 %, 7 %). The corrected pooled lead poisoning percentage in eastern zone (4.3 %, 95 % CI: 2 %, 6.6 %) was slightly lower than that in western zone (5.8 %, 95 % CI: 3.2 %, 8.5 %) and much lower than in central zone (8.5 %, 95 % CI: 4.9 %, 12.1 %). The corrected pooled rate of population living around mining area (70 %, 95 % CI: 62.7 %, 77.3 %) was much higher than that of population in urban area (9.6 %, 95 % CI: 7.1 %, 12.1 %), suburban area (23.6 %, 95 % CI: 17 %, 30.3 %), rural area (23.8 %, 95 % CI: 6.7 %, 40.9 %) and industrial area (57.5 %, 95 % CI: 28 %, 86.9 %). In male population, the corrected pooled rate (10 %, 95 % CI: 7 %, 13 %) was slightly higher than that in female population (7.7 %, 95 % CI: 5 %, 10.4 %). Considering different age groups, the lead poisoning prevalence gradually rose with the increase of age and reached peak level at preschool age, then declined slightly with age. CONCLUSION: This meta-analysis revealed lead exposure situation of Chinese population in recent decades which provide robust evidence for policy making.

Review of the epidemiology, pathogenesis and prevention of atrial fibrillation after pacemaker implantation.

Cardiac pacemaker implantation is an important treatment for symptomatic bradycardia. However, epidemiological data show that the incidence of atrial fibrillation (AF) is significantly higher in patients with implanted pacemakers than in the general population, which may be related to the preoperative presence of multiple risk factors for AF, improvement of diagnostic sensitivity and the pacemaker itself. The pathogenesis of AF after the implantation of pacemaker is related to cardiac electrical remodeling, structural remodeling, inflammation, and autonomic nervous disorder, which are induced by the pacemaker. Moreover, different pacing modes and pacing sites have various effects on the pathogenesis of postoperative AF. Recent studies have reported that reducing the proportion of ventricular pacing, improving the pacing site and setting up special pacing procedures might be highly useful in prevention of AF after pacemaker implantation. This article reviews the epidemiology, pathogenesis, influencing factors, and preventive measures regarding AF after pacemaker surgery.

Determinants affecting the blood mercury levels of preschool children in Shanghai, China: A cross-sectional study.

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.

Successful transcatheter arterial embolization treatment for chest wall haematoma following permanent pacemaker implantation: A case report.

BACKGROUND: Haematoma is one of the main complications associated with pacemaker implantation. Pseudoaneurysm is a rare condition that is not easy to identify and is often overlooked. CASE SUMMARY: A female patient diagnosed with high-grade atrioventricular block underwent permanent pacemaker implantation. During the operation, puncturing a small branch of the right subclavian artery developed into a pseudoaneurysm and resulted in further haematoma formation. Conventional treatment of compression haemostasis and haemostatic drugs was not effective. A series of timely transcatheter arterial embolizations avoided serious complications. CONCLUSION: More possible conditions should be taken into consideration as haematoma is discovered, and timely treatment might prevent severe adverse events.

Effects of prenatal exposure to arsenic on neonatal birth size in Wujiang, China.

To investigate prenatal exposure to arsenic and its effect on birth size, we conducted a cross-sectional study in Wujiang City, Jiangsu, China, from June 2009 to June 2010. A total of 1722 mother-infant pairs were included in the study. A questionnaire was administered to the pregnant women and umbilical cord blood(UCB) samples were collected. Arsenic concentration in UCB was detected by inductively coupled plasma emission mass spectroscopy (ICP-MS). The birth size included birth weight, birth body length and head circumference of the newborns. The effects of arsenic exposure on birth size were assessed by multiple linear regression analysis. Arsenic concentrations in UCB ranged from 0.11 to 30.36 µg/L, the median was 1.71 µg/L. In this range of exposure, arsenic concentration was significantly negatively associated with birth weight, especially among male infants. Our results showed that prenatal exposure to arsenic level was low in Wujiang City, China. However, low prenatal arsenic exposure could have negative effects on birth weight. Our research provided evidence for the adverse effects of prenatal low-level arsenic exposure on the intrauterine growth of the fetus.

Relationship between thyroid hormone parameters and exposure to a mixture of organochlorine pesticides, mercury and nutrients in the cord blood of newborns.

The fetus is prenatally exposed to a mixture of organochlorine pesticides (OCPs), mercury (Hg), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and selenium (Se) through maternal seafood consumption in real-life scenario. Prenatal exposure to these contaminants and nutrients has been suggested to affect thyroid hormone (TH) status in newborns, but the potential relationships between them are unclear and the joint effects of the mixture are seldom analyzed. The aim of the study is to investigate the associations of prenatal exposure to a mixture of OCPs, Hg, DHA, EPA and Se with TH parameters in newborns. 228 mother-infant pairs in Shanghai, China were included. We measured 20 OCPs, total Hg, DHA, EPA and Se in cord blood samples as exposure variables. The total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels and the FT3/FT4 ratio in cord serum were determined as outcomes. Using linear regression models, generalized additive models and Bayesian kernel machine regression, we found dose-response relationships of the mixture component with outcomes: among the contaminants, p,p'-DDE was the most important positive predictor of TT3, while HCB was predominantly positively associated with FT3 and the FT3/FT4 ratio, indicating different mechanisms underlying these relationships; among the nutrients, EPA was first found to be positively related to the FT3/FT4 ratio. Additionally, we found suggestive evidence of interactions between p,p'-DDE and HCB on both TT3 and FT3, and EPA by HCB interactions for TT3, FT3 and FT3/FT4 ratio. However, the overall effects of the mixture on thyroid hormone parameters were not significant. Our result suggests that prenatal exposure to p,p'-DDE, HCB and EPA as part of a mixture might affect thyroid function of newborns in independent and interactive ways. The potential biological mechanisms merit further investigation.

The Role of Short-Chain Fatty Acids of Gut Microbiota Origin in Hypertension.

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases, and its development involves multiple mechanisms. Gut microbiota has been reported to be closely linked to hypertension. Short-chain fatty acids (SCFAs)-the metabolites of gut microbiota-participate in hypertension development through various pathways, including specific receptors, immune system, autonomic nervous system, metabolic regulation and gene transcription. This article reviews the possible mechanisms of SCFAs in regulating blood pressure and the prospects of SCFAs as a target to prevent and treat hypertension.

Spontaneous hemopneumothorax after laparoscopy: a case report and literature review.

BACKGROUND: Spontaneous hemopneumothorax (SHP) is defined as the accumulation of >400 mL of blood in the pleural cavity in association with spontaneous pneumothorax. This rare clinical disorder may be life-threatening. CASE PRESENTATION: A 71-year-old woman presented with a 1-month history of recurrent bloody stool, and electronic colonoscopy suggested a rectal mass. Laparoscopic radical resection of rectal cancer was performed. Two days later, she developed chest tightness, shortness of breath, and slight pain in the left chest. Emergency chest radiography revealed mild left pneumothorax and pleural effusion. SHP was suspected and a thoracic drain was inserted. However, the patient developed hemorrhagic shock 3 hours after drainage. She underwent emergency video-assisted thoracic surgery (VATS), which revealed left lung tip rupture with bleeding and adhesive band fracture at the top of the left thoracic cavity. The ruptured lung tissue was removed and electrocoagulation at the adhesion band was performed for hemostasis. The patient was discharged on postoperative day 11. At the time of this writing, she had developed no SHP recurrence or any other complications. CONCLUSIONS: This case shows that conservative treatment may have serious consequences in patients with SHP. Thus, chest X-ray examination and VATS should be performed in patients with SHP.

[Efficiency of diode laser-assisted methods in direct pulp capping of carious teeth].

PURPOSE: To explore the efficiency of diode laser-assisted methods in direct pulp capping of carious teeth. METHODS: A total of 100 carious teeth were randomly divided into experimental group and control group, 50 in each group. Patients in the control group were treated with conventional treatment, while in the experimental group, 808 nm, 1.5 W laser with fiber diameter of 320 µm was used on the exposure site to control hemorrhage, and 1W laser was used to decontaminate the cavity. SPSS 19.0 software package was used for data analysis. RESULTS: Of 50 patients in the experimental group, three teeth were lost to follow-up, the total effective rate was 89.4%. Of 50 patients in the control group, five teeth were lost to follow-up, the total effective rate was 73.3%. The difference between the two groups was statistically significant (P<0.05). CONCLUSIONS: Laser-assisted procedure in carious exposures is more effective than conventional treatment in pulp-capping therapy, which is worthy of wide application.

Sex differences in the effects of lead exposure on growth and development in young children.

The adverse effects of lead exposure on children's health have been widely investigated. Physical growth is a central indicator of health in early childhood. However, studies on the associations between lead exposure and the physical growth of young children are still equivocal. This study aimed to investigate the effects of lead exposure on young children's growth. A cross-sectional survey was conducted, and a total of 1678 young children were recruited. Blood lead levels were determined by graphite furnace atomic absorption spectrophotometry and anthropometric measurements were obtained by nurses. The weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ) and BMI for-age Z-score (BMIZ) of the children were calculated according to World Health Organization standards. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between lead exposure and childhood anthropometric characteristics. Meanwhile, the sex differences in these associations were also examined. The median blood lead levels in total subjects, in boys and in girls were 46.44, 49.00 and 43.27 µg/L, respectively. After adjusting for confounders, a significantly negative association of blood lead levels with WAZ and HAZ was observed. After stratification by sex, the blood lead levels in children were negatively associated with WAZ and HAZ in boys but not in girls. Meanwhile, we further provide evidence that blood lead levels below 50 µg/L may also have adverse effects on young children's HAZ. Our findings suggest that lead exposure may have sex-specific effects on physical growth in young children and that blood lead level in a low levels may also have adverse effects on children's physical growth and development.

Contemporary blood lead levels of children aged 0-84 months in China: A national cross-sectional study.

Despite the global abundance of studies on children's lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children's Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0-84 months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1 µg/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7 µg/L, with 8.6% of BLLs exceeding 50 µg/L. Boys had higher BLLs (GM 27.2 µg/L) compared to girls (GM: 25.9 µg/L) (p < 0.001). Children at the age of 0-36 months had a lower PbB (GM 25.7 µg/L) level compared with those aged 36-84 months (GM 27.9 µg/L) (p < 0.001). When taking into account sociodemographic factors, a multivariate logistic regression analysis shows that the odds ratios (OR) of having a BLL of 27 µg/dL (i.e., median BLL of this study) or higher were 1.88 (95% CI: 1.76, 2.02) and 1.35 (95% CI: 1.22, 1.49) for homes using coal and biomass fuels, respectively, compared to those using gas or electricity. Meanwhile, children in homes close to roads were more likely to have BLLs exceeding 27 µg/dL (OR: 1.11, 95% CI: 1.03, 1.20). In China, rural children had higher BLLs compared to urban children. As a result of pediatric exposure to Pb, there were approximately 144 million and 36 million IQ points lost for rural children and urban children, respectively, revealing a disparity of Pb exposure between rural and urban areas in China. Cleaner domestic fuels and improved cooking/heating equipment will reduce contemporary Pb exposure in rural areas. In addition, the association between contemporary BLLs and distance away from roads further suggests that resuspension of legacy soil/dust Pb should not be neglected in future remediation programs and household interventions. As a large scale survey, this study provides evidence for revising the reference value of BLL, improving the guideline for clinical and public health management, and implementing interventions to prevent adverse health outcomes associated with low-level Pb exposure in children.

Programmed death-ligand 1 and survival in colorectal cancers: A meta-analysis.

BACKGROUND: Programmed death-ligand 1 (PD-L1) is a programmed death 1 (PD-1) ligand that plays a pivotal role in the inhibition of the T-cell-mediated immune response. The expression of PD-L1 is associated with the prognosis and clinical outcomes of multiple tumors. However, the prognostic value of PD-L1 overexpression in colorectal cancer is still controversial. In this study, we sought to clarify this by presenting a meta-analysis of relevant studies. METHODS: Databases including PubMed, Web of Science, and EMBASE were systematically searched for studies concerning the expression of PD-L1 and survival in colorectal cancer. The reported hazard ratios (HR) with 95% confidence intervals (CI) of overall survival, disease-free survival, and recurrence-free survival in the included studies were analyzed by fixed effects/random effects models. RESULTS: Fifteen studies involving 3078 patients with colorectal cancer were included in our meta-analysis. Overexpression of PD-L1 was found to be associated with poor overall survival (HR 1.83; 95% CI 1.21, 2.79; P = 0.005) and poor recurrence-free survival (HR 2.78; 95% CI 1.43, 5.42; P = 0.003). However, no correlation was found between PD-L1 overexpression and poor disease-free survival (HR 1.23; 95% CI 0.83, 1.82; P = 0.305). Overexpression of PD-L1 indicating poor survival held true across different geographical areas, sample sizes, analysis types, sources of HRs, and cell types. CONCLUSION: Overexpression of PD-L1 is associated with worse prognosis in patients with colorectal cancer and can guide physicians in the application of PD-1/PD-L1 immune checkpoint-targeted therapy.

Relation of prenatal low-level mercury exposure with early child neurobehavioral development and exploration of the effects of sex and DHA on it.

BACKGROUND: The extent to which low-level, in utero mercury exposure affects child neurobehavioral development during early childhood has been inconclusive. In addition, the effects of sex and docosahexaenoic acid (DHA) on these relationships remain unclear and controversial. OBJECTIVES: This study aimed to explore the associations between prenatal low-level mercury exposure and child neurobehavioral development during the neonatal and toddler periods and to examine the potential confounding or interactive effects of sex and DHA status on these relationships. METHODS: This longitudinal study included 286 mother-child pairs in Shanghai, China, whose cord blood samples were analyzed for total mercury, DHA, other nutrients and coexposure contaminants possibly due to maternal consumption of seafood. Children's neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment (NBNA) three days after birth and the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months of age. RESULTS: Cord blood mercury concentration, with geometric mean of 2.00 µg/l, was related to poorer NBNA performance but unrelated to BSID-III scores with adjustment for DHA and other covariates. Cord serum DHA was positively associated with motor development assessed by the BSID-III. The interaction was found between mercury and DHA on the NBNA score, and the inverse relation of cord blood mercury with NBNA was significant only among the children with lower DHA levels (<45.54 µg/ml). Additional adjustment for DHA didn't change the associations between cord blood mercury and neurodevelopmental outcomes substantially. The mercury by sex interaction for language of BSID-III was borderline significant. CONCLUSIONS: Our research provides initial evidence for the negative effects of prenatal low-level mercury exposure on neonates' neurobehavioral development. Prenatal DHA status may modify the relationship between cord blood mercury level and neonatal neurobehavioral development, but the confounding effects of DHA were not observed. Further studies are warranted before the causality of the observed associations can be determined.

Effects of lead, mercury, aluminium and manganese co-exposure on the serum BDNF concentration of pre-school children in Taizhou, China.

Previous studies have shown that toxic metal exposure can have adverse effects on the nervous system of children, but the toxicology of metal co-exposure on neurodevelopment remains to be clarified. Brain derived neurotrophic factor (BDNF) plays an important role in nervous system development, but the possible effects of metal co-exposure on the serum BDNF concentrations of children remain unknown. A total of 561 children living in Taizhou City, China were recruited to participate in our cross-sectional multicenter survey. We measured their blood Pb, Hg, Al and Mn levels and serum BDNF concentrations as well as determined their associations in the total and within sex subgroups. The geometric means of the blood Pb, Hg, Al and Mn levels in all the participants were 67.18 µg/L, 1.01 µg/L, 52.03 µg/L and 18.26 µg/L, respectively. The serum BDNF concentration in children was 19.45 ng/mL. After adjusting for confounders, the blood Pb levels were significantly negatively associated with the serum BDNF concentrations in all the subjects and boys but not in girls. In addition, a significantly negative interaction between blood Pb and blood Hg and a positive interaction between blood Pb and blood Al on serum BDNF concentrations were also observed in boys but not in girls. Our findings highlight the toxic effects of metal co-exposure on serum BDNF levels in pre-school children and indicate that these effects might differ by gender, which suggest that special attention should be paid to the sex-specific effects of metal exposure.