A body map of somatic mutagenesis in morphologically normal human tissues.

Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual.

Effect of fine particulate matter exposure on gestational diabetes mellitus risk: a retrospective cohort study.

BACKGROUND: The literature on the association between fine particulate matter (PM2.5) exposure and gestational diabetes mellitus (GDM) risk has focused mainly on exposure during the first and second trimesters, and the research results are inconsistent. Therefore, this study aimed to investigate the associations between PM2.5 exposure during preconception, the first trimester and second trimester and GDM risk in pregnant women in Guangzhou. METHODS: A retrospective cohort study of 26 354 pregnant women was conducted, estimating PM2.5, particulate matter with a diameter >10 µm (PM10), sulphur dioxide (SO2), carbon monoxide (CO) and ozone (O3) exposure during preconception and the first and second trimesters. Analyses were performed using Cox proportional hazards models and nonlinear distributed lag models. RESULTS: The study found that exposure to PM2.5 or a combination of two pollutants (PM2.5+PM10, PM2.5+SO2, PM2.5+CO and PM2.5+O3) was found to be significantly associated with GDM risk (P < 0.05). In the second trimester, with significant interactions found for occupation and anaemia between PM2.5 and GDM. When the PM2.5 concentrations were ≥19.56, ≥25.69 and ≥23.87 µg/m3 during preconception and the first and second trimesters, respectively, the hazard ratio for GDM started to increase. The critical window for PM2.5 exposure was identified to be from 9 to 11 weeks before conception. CONCLUSIONS: Our study results suggest that PM2.5 exposure during preconception and the first and second trimesters increases the risk of GDM, with the preconception period appearing to be the critical window for PM2.5 exposure.

Inhibition of TMEM16A improves cisplatin-induced acute kidney injury via preventing DRP1-mediated mitochondrial fission.

Acute kidney injury (AKI) is associated with high morbidity and mortality. Our previous study has demonstrated that TMEM16A, a Ca2+-activated chloride channel, contributes to renal fibrosis progression in chronic kidney disease. However, whether TMEM16A is involved in AKI is still unknown. In this study, we established cisplatin AKI mice model and found that TMEM16A expression was upregulated in the injured kidney. In vivo knockdown of TMEM16A effectively prevented cisplatin-induced tubular cell apoptosis, inflammation and kidney function loss. Western blot and transmission electron microscopy (TEM) revealed that TMEM16A knockdown inhibited Drp1 translocation from the cytoplasm to mitochondria and prevented mitochondrial fission in tubular cells. Consistently, in cultured HK2 cells, knockdown or inhibition of TMEM16A by shRNA or its specific inhibitor suppressed cisplatin-induced mitochondrial fission and its associated energy dysfunction, ROS accumulation, and cell apoptosis via inhibiting Drp1 activation. Further investigation showed that genetic knockdown or pharmacological inhibition of TMEM16A inhibited cisplatin-induced Drp1 Ser-616 site phosphorylation through ERK1/2 signaling pathway, whereas overexpression of TMEM16A promoted this effect. Treatment with Drp1 or ERK1/2 inhibitor could efficiently prevent cisplatin-induced mitochondrial fission. Collectively, our data suggest that TMEM16A inhibition alleviated cisplatin-induced AKI by preventing tubular cell mitochondrial fission through the ERK1/2 / Drp1 pathway. Inhibition of TMEM16A may be a novel therapeutic strategy for AKI.

Role of body mass index in pregnancy outcomes after emergency cerclage for cervical insufficiency in singleton pregnant patients.

BACKGROUND: The study aims were to analyze pregnancy outcomes after the use of emergency cerclage in patients with different BMIs. METHODS: A total of 76 singleton pregnant patients who underwent emergency cerclage at a tertiary comprehensive hospital in China between Jan 2017 and Dec 2021 were retrospectively divided into an obesity group of 37 patients with BMIs ≥ 28 kg/m2 and a non-obesity group of 39 patients with BMIs < 28 kg/m2. The medical records of patients were reviewed and all relevant clinical data were further collected into an itemized data spreadsheet for various analyses. RESULTS: Emergent cerclage, along with amnioreduction if needed, could be safely performed on both obese and non-obese pregnant women with a dilated external cervix (> 1 cm), which effectively prolonged the gestational week up to ≥ 25 weeks. Obese gravidae had shorter suture-to-delivery intervals and mean pregnancy lengths but more spontaneous preterm births before 37 weeks, and a lower live birth rate (P < 0.05). Logistic regression analysis revealed that BMI, how many times cerclages have been performed during pregnancy (frequency of cerclage) and bacterial vaginosis, aerobic vaginitis and vulvovaginal candidiasis (vaginal microecology) were significantly correlated with fetal loss (P < 0.05), while rank correlation analysis established a negative correlation between BMI values and the suture-to-delivery interval (P = 0.031). CONCLUSIONS: Pregnant cervical insufficiency patients with BMIs > 28 kg/m2 may ill-serve the gestational outcomes and suture-to-delivery interval after their emergent cerclage. Additionally, BMI, frequency of cerclage and vaginal microecology accounted for higher fetal loss in patients who underwent emergency cerclage.

Mixed-Valence CuI /CuIII Metal-Organic Frameworks with Non-innocent Ligand for Multielectron Transfer.

We report two novel three-dimensional copper-benzoquinoid metal-organic frameworks (MOFs), [Cu4 L3 ]n and [Cu4 L3 ⋅ Cu(iq)3 ]n (LH4 =1,4-dicyano-2,3,5,6-tetrahydroxybenzene, iq=isoquinoline). Spectroscopic techniques and computational studies reveal the unprecedented mixed valency in MOFs, formal Cu(I)/Cu(III). This is the first time that formally Cu(III) species are witnessed in metal-organic extended solids. The coordination between the mixed-valence metal and redox-non-innocent ligand L, which promotes through-bond charge transfer between Cu metal sites, allows better metal-ligand orbital overlap of the d-π conjugation, leading to strong long-range delocalization and semiconducting behavior. Our findings highlight the significance of the unique mixed valency between formal Cu(I) and highly-covalent Cu(III), non-innocent ligand, and pore environments of these bench stable Cu(III)-containing frameworks on multielectron transfer and electrochemical properties.

New-Onset Atrial Fibrillation After Cardiac Surgery is a Significant Risk Factor for Long-Term Stroke: An Eight-Year Prospective Cohort Study.

OBJECTIVES: This study sought to determine the incidence and significance of new-onset atrial fibrillation as a risk factor for long-term stroke and mortality after cardiac surgery. DESIGN: A prospective cohort study. SETTING: Two large tertiary public hospitals. PARTICIPANTS: The study comprised 3008 patients who underwent coronary artery bypass grafting and/or valve surgery from 2008 to 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: New-onset atrial fibrillation was analyzed as a risk factor for postoperative stroke using a multivariate logistic regression model after adjustment for potential confounders. A Cox regression model with time-dependent variables was used to analyze relationships between new-onset atrial fibrillation and postoperative survival. New-onset atrial fibrillation was detected in 573 (19.0%) patients. Stroke occurred in 234 (7.8%) patients during the mean postoperative follow-up period of six ± two years. The incidence of postoperative stroke in patients with new-onset atrial fibrillation (9.9%) and patients with both preoperative and postoperative atrial fibrillation (13.8%) was higher than in patients with no atrial fibrillation (6.8%) (p = 0.002). New-onset atrial fibrillation (odds ratio, 1.53; 95% confidence interval [CI], 1.08-2.18; p = 0.017) was identified as an independent risk factor for postoperative stroke. A total of 518 (17.2%) mortalities occurred within the mean postoperative follow-up period of eight ± two years. New-onset atrial fibrillation was associated with shorter survival (hazard ratio, 1.49; 95% CI, 1.22-1.81; p < 0.001) compared with patients with no atrial fibrillation. CONCLUSIONS: New-onset atrial fibrillation is a significant risk factor for long-term stroke and mortality after cardiac surgery. Close monitoring and treatment of this condition may be necessary to reduce the risk of postoperative stroke and mortality.

Maternal risk factors and pregnancy complications associated with low birth weight neonates in preterm birth.

AIM: To explore the association between common pregnancy complications and low birth weight (LBW) neonates in preterm birth. METHODS: The study included 1764 pregnant women who experienced a single birth prematurely at a city hospital in Guangzhou, China between January 1, 2017 and December 31, 2019. A total of 874 normal birth weight neonates and 890 LBW neonates were included. Multivariate logistic regression analysis was conducted to identify and measure risk factors; two-tailed test was applied, with a p ≤ 0.05 considered statistically significant. RESULTS: Hypertension was the primary risk factor of LBW in preterm neonates, odds ratio (OR) = 2.912 (p < 0.001; 95% confidence interval [CI], 2.044-4.149), followed by hypothyroidism, OR = 1.807 (p = 0.046; 95% CI, 1.012-3.226), placental abruption, OR = 1.759 (p = 0.049; 95% CI, 1.002-3.087), reproductive tract infection, OR = 1.746 (p < 0.001; 95% CI, 1.325-2.301), abnormal amniotic fluid volume, OR = 1.737 (p = 0.003; 95% CI, 1.202-2.501), and fetal distress OR = 1.690 (p = 0.012; 95% CI, 1.120-2.551). CONCLUSION: Preventing risk factors, such as hypertension, hypothyroidism, and reproductive tract infections, during pregnancy may reduce the incidence of LBW neonates.

Cerebrospinal fluid of chronic osteoarthritic patients induced interleukin-6 release in human glial cell-line T98G.

BACKGROUND: Chronic osteoarthritic pain is not well understood in terms of its pathophysiological mechanism. Activated glial cells are thought to play a role in the maintenance of chronic pain. T98G glioblastoma cell line was previously observed to release higher amounts of interleukin-6 (IL-6) when treated with cerebrospinal fluid (CSF) from patients with another chronic pain condition, post-herpetic neuralgia. In this study, we investigated the ability of CSF from patients diagnosed with knee osteoarthritis suffering from chronic pain, to trigger the release of pro-inflammatory cytokines, IL-6, IL-1beta and tumour necrosis factor alpha (TNF-α) from T98G. Characterization of upstream signalling was also explored. METHODS: Fifteen osteoarthritis patients undergoing total knee replacement due to chronic knee pain and 15 patients without pain undergoing other surgeries with spinal anaesthesia were prospectively recruited. CSF was collected during anaesthesia. CSF were added to cultured T98G cells in the presence of lipopolysaccharide. IL-6, IL-1ß and TNF-α release from T98G cells were measured using enzyme immunoassay. Antibody array and western blotting were performed using CSF-triggered T98G cell lysates to identify possible signalling targets. Age, gender and pain scores were recorded. Mann-Whitney U test was used to compare IL-6 release and protein expression between groups. Association between IL-6 and pain score was analysed using linear regression. RESULTS: Significant higher levels of IL-6 were released by T98G cells when induced by osteoarthritis patients' CSF in the presence of LPS. The IL-6 levels showed positive association with pain score (adjusted B estimate = 10.1 (95% Confidence Interval 4.3-15.9); p = 0.001). Antibody array conducted with 6 pooled T98G cell lysate induced with osteoarthritis pain patient CSF identified greater than 2-fold proteins including STE20-related kinase adaptor protein and spleen tyrosine kinase. Further validation done using western blotting of individual CSF-triggered T98G cell lysate showed non-significant increase. CONCLUSION: Higher IL-6 release from T98G when triggered by OA-CSF, in the presence of LPS, suggest the presence of "unknown molecule" in CSF that may be crucial in the maintenance phase of chronic pain in our osteoarthritis population. Further studies on the signalling pathways involved in pain and relevance of IL-6 release from T98G cells in other pain models are needed.

The neglected perioperative population of undiagnosed diabetics - a retrospective cohort study.

BACKGROUND: Diabetes is known to increase morbidity and 30-day mortality in adults undergoing non-cardiac surgery, but longer term outcomes are less studied. This study was done to explore how undiagnosed and known diabetes affect 30-day and one-year morbidity and mortality outcomes. The secondary aim was to study the prevalence of undiagnosed diabetics in our perioperative Asian surgical population. METHODS: A retrospective cohort study of 2106 patients aged > 45 years undergoing non-cardiac surgery in a single tertiary hospital was performed. Undiagnosed diabetics were identified (HbA1c ≥6.5% or fasting blood glucose ≥126 mg/dL) and relevant demographic, clinical and surgical data were analyzed to elicit the relationship to adverse outcomes. Univariate analysis was first performed to identify significant variables with p-values ≤0.1, which were then analyzed using multiple logistic regression to calculate the adjusted odds ratio. RESULTS: The prevalence of undiagnosed diabetes was 7.4%. The mean and median HbA1c of known diabetics were 7.9 and 7.5%, while the mean and median HbA1c for undiagnosed diabetics were 7.2 and 6.8% respectively. 36.4% of known diabetics and 20.5% of undiagnosed diabetics respectively had a random blood glucose > 200 mg/dL. Undiagnosed diabetics had a three-fold increase in 1-year mortality compared to non-diabetics (adjusted OR 3.46(1.80-6.49) p < 0.001) but this relationship was not significant between known and non-diabetics. Compared to non-diabetics, known diabetics were at increased risks of new-onset atrial fibrillation (aOR 2.48(1.01-6.25) p = 0.047), infection (aOR 1.49(1.07-2.07) p = 0.017), 30-day readmission (aOR 1.62(1.17-2.25) p = 0.004) and 30-day mortality (aOR 3.11(1.16-8.56) p = 0.025). CONCLUSIONS: Although undiagnosed diabetics have biochemically less severe disease compared to known diabetics at the point of testing, they are at a one-year mortality disadvantage which is not seen among known diabetics. This worrying trend highlights the importance of identifying and treating diabetes. Congruent to previous studies, known diabetics have higher morbidity and 30-day mortality compared to non-diabetics.

Prediction of failed facemask ventilation: new scoring system for difficult airway.

BACKGROUND: We previously have shown that there was a strong correlation between failed facemask ventilation, failed ventilation through a supraglottic airway, and difficult tracheal intubation. The primary aim of this study was to evaluate whether or not an established method to predict difficult ventilation through a supraglottic airway was also useful for predicting failed facemask ventilation. METHODS: This was a single-center, retrospective observational study. We studied 28,081 anesthetized patients in whom ventilation through a facemask, and supraglottic airway was attempted as the initial technique during induction of anesthesia, between May 2011 and March 2016. For each patient, the score which had been validated to be useful for predicting difficult ventilation through a supraglottic airway was calculated. The score ranged between 0 and 7 points, and we defined a low risk when the score was 0-3, and a high risk when the score was 4-7. To measure and compare the predictive accuracy of the score, we generated a receiver operating characteristic curve and compared the area under the curve (AUC). RESULTS: The incidence of failed facemask ventilation was significantly higher in patients with high-risk predictive score than in patients with low-risk predictive score [0.38% vs 0.056%, odds ratio 6.8 (95% CI 2.6-18.1, p value = 0.002)], and the sensitivity of the score was 25%, while the specificity was 95%, with a negative predictive value of 99%. The AUC of the score was 0.71 (95% CI 0.58-0.83). CONCLUSIONS: The predictive score for difficult ventilation through a supraglottic airway is also useful to predict failed facemask ventilation.

Association Between Ethnicity and Postoperative Hyperglycemia in a Southeast Asian Population Undergoing Cardiac Surgery.

OBJECTIVE: Postoperative hyperglycemia is a known risk factor for adverse outcomes following cardiac surgery. Therefore, the authors investigated the association between ethnicity and postoperative hyperglycemia in a Southeast Asian multiethnic population undergoing cardiac surgery. DESIGN: Perioperative data were analyzed prospectively. SETTING: Perioperative data were obtained from 2008 to 2010 at the 2 main heart centers in Singapore. PARTICIPANTS: Data from 911 adult patients were collected. INTERVENTIONS: All patients underwent elective cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Perioperative variables, genetic associations, and outcomes of hyperglycemic versus normoglycemic patients were compared. Of the 911 patients analyzed, 47.7% (n = 435) were diabetic and 77.7% (n = 708) had postoperative hyperglycemia. Patients with postoperative hyperglycemia after cardiac surgery were more likely to have diabetes; be female, older, and more obese; and have hypertension and renal impairment. Patients of Indian ethnicity had a significantly higher incidence of postoperative hyperglycemia (86.7%, p = 0.043), as compared to Malays (79.1%) and Chinese (75.9%). Ethnicity was identified as an independent risk factor for postoperative hyperglycemia, with Indians having a significantly higher risk than Chinese (OR 2.115, p = 0.015). Although Indian ethnicity was associated with the presence of angiotensin-converting enzyme D allele (65.7%, p = 0.044), no genetic associations with postoperative hyperglycemia were identified. Postoperative hyperglycemia also was associated significantly with poorer outcomes of longer high-dependency unit stay and new-onset cardiac arrhythmias. CONCLUSION: The authors' findings demonstrated Indian ethnicity as an independent risk factor of postoperative hyperglycemia, likely due to insulin resistance and exaggerated hyperglycemic stress response, emphasizing the need for ethnic-based data unique to each population group.

Acute kidney injury increases the risk of end-stage renal disease after cardiac surgery in an Asian population: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality. The long-term association between AKI and end-stage renal disease (ESRD) in an Asian population is unknown. Given the high prevalence of diabetes and a younger age of presentation for cardiac surgery, it is important to track this progression of kidney disease. Therefore, we studied the long-term risk of ESRD and mortality in our Asian patients who developed AKI after cardiac surgery. METHODS: With ethics approval, we prospectively recruited 3008 patients who underwent cardiac surgery in Singapore between 2008 and 2012, and followed them up till 2014. ESRD and mortality information were obtained from the Singapore Renal Registry and Singapore Registry of Births and Deaths respectively. AKI was defined using the Acute Kidney Injury Network (AKIN) criteria, and ESRD was defined as stage 5 chronic kidney disease requiring renal replacement therapy. The Cox proportional hazards regression model was used to analyze associations between AKI and the primary outcome of ESRD and the secondary outcome of death. RESULTS: The AKI incidence was 29.1%. During a mean follow-up of 4.4 ± 2.8 years, 0.9% developed ESRD. The hazard ratio (HR) for developing ESRD was 4.7 (95% C.I. = 1.736-12.603, p = 0.002) for AKIN stage 1 patients, and 5.8 (95% C.I. = 1.769-18.732, p = 0.004) for AKIN stage 2 and 3 patients; while the HR for mortality was 1.7 (95% C.I. = 1.165-2.571, p = 0.007) for AKIN stage 1 patients, and 2.5 (95% C.I. = 1.438-4.229, p < 0.001) for AKIN stage 2 and 3 patients. CONCLUSIONS: AKI is associated with ESRD and mortality after cardiac surgery in our Asian population. The trajectory from AKI to ESRD is rapid within 5 years of cardiac surgery. A concerted periodic follow-up assessment is advocated for AKI patients post-cardiac surgery.

A Clinical Prediction Model for Postcardiac Surgery Atrial Fibrillation in an Asian Population.

BACKGROUND: Postoperative atrial fibrillation (AF) is associated with increased morbidity, mortality, and resource utilization. Current prediction models for postoperative AF are based primarily on Western populations. In this study, we sought to develop a clinical prediction rule for postcardiac surgery AF for a multiethnic Asian population. METHODS: Two thousand one hundred sixty-eight patients undergoing coronary artery bypass graft or valve surgery with cardiopulmonary bypass were prospectively enrolled in this observational study between August 2008 and July 2012 at Singapore's 2 national heart centers. Postoperative AF was defined as an irregularly irregular electrocardiogram rhythm without identifiable P wave after surgery and before hospital discharge that lasted more than an hour, or affected hemodynamics (ie, systolic blood pressure <90 mm Hg or mean arterial blood pressure <60 mm Hg), or required medical treatment. Patients had continuous telemetry monitoring for at least 72 hours while in the intensive care or high-dependency units postoperatively. Subsequently, patients had a 12-lead electrocardiogram daily and when symptomatic. Multivariable logistic regression was used to determine significant predictors of postcardiac surgery AF, and a scoring system was developed. The model was internally validated in an additional 500 patients. RESULTS: Postoperative AF occurred in 17.3% of patients, with a peak occurrence in the first 72 hours after surgery. Multivariate logistic regression analysis identified age ≥65 years (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.11-1.85, P = 0.005), history of AF (OR, 3.65; 95% CI, 2.52-5.30, P < 0.001), inotrope use (OR, 1.74; 95% CI, 1.31-2.32, P < 0.001), cardiopulmonary bypass duration >120 minutes (OR, 1.92; 95% CI, 1.47-2.52, P < 0.001), and Chinese ethnicity (Chinese versus Indian OR, 2.09; 95% CI, 1.28-3.41, P = 0.003) or Malay (Malay versus Indian OR, 2.43; 95% CI, 1.36-4.05, P = 0.002) to be independently associated with postoperative AF. The area under the receiver-operator characteristic curve of the model was 0.704 (95% CI, 0.674-0.734). Internal validation produced an area under the receiver-operator characteristic curve of 0.756 (95% CI, 0.690-0.821). CONCLUSIONS: Clinical risk factors for AF after cardiac surgery in an Asian population are similar to that reported from primarily Western populations, but specific ethnicity influences susceptibility.

Persistent kidney injury at hospital discharge after cardiac surgery with cardiopulmonary bypass in patients with normal preoperative serum creatinine and normal estimated glomerular filtration rate.

OBJECTIVE: Acute kidney injury is a serious complication after cardiac surgery. Although it resolves in most cases, a significant portion of patients persistently have raised creatinine values at hospital discharge. These patients are at greater risk for developing chronic kidney disease and mortality. Therefore, the present study aimed to ascertain risk factors of persistent acute kidney injury after cardiac surgery in patients with normal preoperative renal function. DESIGN: Prospective cohort study. SETTING: Tertiary heart centers. PARTICIPANTS: 2,181 adult cardiac surgical patients, predominantly Asian. INTERVENTIONS: Cardiac surgery between August 2008 and July 2012. MEASUREMENTS AND MAIN RESULTS: The incidence of acute kidney injury, as defined by the Acute Kidney Injury Network stage 1 criteria, was 21.7%. At discharge, 10.5% of these patients had persistent kidney injury, which was defined as a ≥ 26.4 µmol/L (≥ 0.3 mg/dL) difference between preoperative and discharge creatinine levels and/or a 50% rise in serum creatinine. These patients were more likely to be aged ≥ 70 years (relative risk = 2.232, 95% confidence interval = 1.326-3.757, p = 0.003), have a higher peak postoperative creatinine value within 48 hours (relative risk = 1.007, 95% confidence interval = 1.004-1.010, p<0.001), and have lower hemoglobin on intensive care unit arrival (relative risk = 0.759, 95% confidence interval = 0.577-0.998, p = 0.048). CONCLUSIONS: Age ≥ 70 years, higher peak postoperative creatinine within 48 hours, and lower hemoglobin on intensive care unit arrival are associated with persistent acute kidney injury. Strategies to improve hemoglobin on intensive care unit arrival potentially can reduce persistent acute kidney injury. The authors recommend that patients aged ≥ 70 years undergo further renal evaluation for better risk stratification.

Association between air pollution exposure and gestational diabetes mellitus in pregnant women: a retrospective cohort study.

The global prevalence of gestational diabetes mellitus (GDM) is increasing annually, and previous research reports on the relationship between exposure to air pollutants and GDM are not completely consistent. We investigated the association between air pollutant exposure and GDM in pregnant women in a retrospective cohort study in Guangzhou. We found that in the first trimester, exposure to PM2.5 and CO showed a significant association with GDM. In the second trimester, exposure to PM10 was significantly associated with GDM. In the third trimester, exposure to PM2.5, PM10, NO2, SO2, and CO at IQR4 (odds ratio [OR] = 1.271, 95% confidence interval [CI]: 1.179-1.370; OR = 1.283, 95% CI: 1.191-1.383; OR = 1.230, 95% CI: 1.145-1.322; OR = 1.408, 95% CI: 1.303-1.522; OR = 1.150, 95% CI: 1.067-1.240, respectively) compared with IQR1 was positively associated with GDM. However, exposure to NO2 was negatively associated with GDM in the first and second trimesters, and O3 was negatively associated with GDM in the second and third trimesters. We found that the correlation between air pollutants and GDM in different trimesters of pregnancy was not completely consistent in this retrospective cohort study. During pregnancy, there may be an interaction between air pollutant exposure and other factors, such as pregnant women's age, occupation, anemia status, pregnancy-induced hypertension status, and pregnancy season.

Real-world effectiveness of regorafenib in the treatment of patients with metastatic colorectal cancer: A retrospective, observational study.

AIM: To evaluate the real-world usage pattern and factors associated with the effectiveness of regorafenib in patients with metastatic colorectal cancer (mCRC). METHODS: This retrospective study analyzed data for 209 patients with mCRC treated with regorafenib as third or later line of therapy. TheKaplan-Meier method was used to draw the survival curves. Cox proportional hazard regression models were used to analyze the prognostic value for overall survival (OS). RESULTS: Of 209 patients, 156 (75%) were treated with regorafenib, and 53 (25%) were given regorafenib combined with programmed cell death-1 (PD-1) inhibitors. About 182 (87%) patients had a dose record of regorafenib. The initial daily doses of regorafenib were 160, 120, 80, and 40 mg, accounting for 29%, 17%, 48%, and 6% of patients, respectively. The median follow-up time was 11.3 months, and the median OS was 12.0 months (95% CI: 9.7-14.3). Patients treated with PD-1 inhibitors plus regorafenib had a longer OS than the non-PD-1 group (13.5 vs. 10.1 months, hazard ratio [HR] = .534, 95% CI: .325-.879; p = .014). A total of 49 patients with microsatellite stable or mismatch repair-proficient genotype treated with PD-1 inhibitors plus regorafenib had a longer OS than the non-PD-1 group (13.5 vs. 9.7 months; HR = .563, p = .027). The median OS of patients continuing treatment with regorafenib after progression (n = 19, with five patients receiving additional immunotherapy) was marginally longer than patients discontinuing regorafenib after progression (12.7 vs. 11.9 months, p = .425) observed in a smaller cohort. CONCLUSION: In real-world practice, patients with mCRC in whom standard regimens had failed have a good survival benefit with regorafenib. Combination with PD-1 inhibitor may further prolong survival of the patients.

The change in the relationship between temperature and respiratory diseases among children in Guangzhou, China.

Temperature is closely associated with respiratory disease (RD) in children, but few studies have examined whether the relationship between ambient temperature and RD in children changed after the COVID-19 epidemic. The aim of this study was to assess the relationship between temperature and RD in children after the COVID-19 epidemic in Guangzhou, China. We used a distributed lag nonlinear model to compare the relationship between temperature and RD among children in Guangzhou from 2018 to 2022. The results showed an S-shaped relationship between temperature and RD in the post-COVID-19 period with a reference minimum risk at a temperature of 21 °C and an increasing relative risk (RR) at extremely low temperature (ELT) and extremely high temperature (EHT). The highest RR associated with EHT was 1.935 (95% confidence interval [CI]: 1.314-2.850) at a lag of 0-14 days. The on-the-day lag effects were found to be strongest at the lag 0 day of EHT with a RR of 1.167 (95% CI: 1.021-1.334). Furthermore, each 1 °C increase in post-COVID-19 temperature increased the risk of RD by 8.2% (95% CI: 1.044-1.121). Our study provides evidence that the relationship between temperature and RD in children in Guangzhou changed after the COVID-19 epidemic, and high temperature is more likely to cause RD in children. Relevant government departments and parents should understand the relationship between temperature and RD in children and develop new preventive measures.

Colonisation of Group B Streptococcus and its effects on pregnancy outcomes in pregnant women in Guangzhou, China: a retrospective study.

OBJECTIVES: This study was to investigate the colonisation rate of Group B Streptococcus (GBS) during pregnancy, and to evaluate the influence of GBS colonisation on pregnancy outcomes. DESIGN: A retrospective cohort study. SETTING: Data of 47 380 pregnant women from 2016 to 2022 were collected from the Maternal and Child Health Hospital of Huadu District, Guangzhou City, China. PARTICIPANTS: A total of 15 040 pregnant women were eligible for this study, of which 32 340 were excluded due to non-native pregnant women, in vitro fertilization infants, malformed fetuses, habitual abortion, abortions due to poor reproductive or obstetrical history, artificial insemination, umbilical cord torsion, and other diseases during pregnancy. PRIMARY OUTCOME MEASURES: The incidence rates of GBS colonisation and premature delivery, fetal distress, premature rupture of membranes (PROM), low birth weight (LBW), abortion and stillbirth. RESULTS: Of the 15 040 pregnant women included in this study, 1445 developed GBS colonisation, with a prevalence of 9.61% (95% CI, 9.15 to 10.09). Advanced maternal age (≥35 years) predisposed women to GBS colonisation, and the occurrence of GBS colonisation varied among different ethnic groups. Our data revealed that fetal distress, PROM and LBW were more common in pregnant women colonised with GBS than in pregnant women not colonised with GBS. The incidence for premature delivery, fetal distress, PROM and LBW in infants of pregnant women colonised with GBS was 41.0% (OR=1.410, 95% CI, 1.134 to 1.753), 282.5% (OR=3.825, 95% CI, 3.185 to 4.593), 14.9% (OR=1.149, 95% CI, 1.005 to 1.313), and 29.7% (OR=1.297, 95% CI, 1.010 to 1.664), respectively. CONCLUSIONS: GBS colonisation was relatively low in pregnant women in Guangzhou. Women of advanced maternal age were more prone to GBS colonisation, and pregnant women colonised with GBS were more predisposed to fetal distress, PROM and LBW.

Glycated Casein by TGase-Type Exerts Protection Potential against DSS-Induced Colitis via Inhibiting TLR4/NF-κB Signaling Pathways in C57BL/6J Mice.

Glycation by transglutaminase (TGase)-type could effectively improve the structure and functional properties of proteins. However, the influence on intestinal inflammation or the underlying mechanisms has not been investigated. The goal of this research was to compare the bioactivities between glycated casein generated from the TGase-catalyzed reaction and oligochitosan as well as casein using a mouse model of dextran sulfate sodium (DSS)-induced intestinal inflammation to examine the protective effects and the underlying mechanism of glycated casein on intestinal inflammation. Eight groups of C57BL/6 mice were randomly assigned in this study: Control group: standard diet for 35 days; Model group: standard diet for 28 days and then colitis induction; Pretreated groups: different levels (200, 400, 800 mg/kg BW) of casein or glycated casein for 28 days before colitis induction. The mice were drinking water containing a 3% DSS solution for seven days of mice to cause colitis. The results indicated that glycated casein and casein at 200-800 mg/kg BW all relieved DSS-induced weight loss, reduced disease activity index (DAI) score, alleviated colon length shortening, weakened the destruction of colonic mucosal structure, decreased serum LPS, and MPO, IL-1ß, IL-6 and TNF-α levels in serum and colon, as well as regulated the expression of proteins involved in the TLR4/NF-κB signaling pathway in a concentration-dependent manner. Glycated caseinate showed a better protective effect against DSS-induced colitis than casein, highlighting that the TGase-type glycation of proteins as a potential functional food ingredient might be a helpful method for gut health.

Efficacy and safety of regorafenib as second-line treatment for patients with hepatocellular carcinoma and macrovascular invasion and(or) extrahepatic metastasis.

Background: Macrovascular invasion and(or) extrahepatic metastasis are the main clinical characteristics of Chinese patients with hepatocellular carcinoma (HCC) after entering the second-line treatment. The aim of this study was to explore the efficacy and safety of regorafenib as a second-line treatment for these patients with HCC. Methods: We selected 253 patients with primary liver cancer who were treated in Henan Cancer Hospital from June 2017 to September 2020. According to the inclusion and exclusion criteria, 63 patients with HCC with macrovascular invasion and/or extrahepatic metastasis were finally included. The clinical data of patients were obtained by consulting the electronic medical record system and through telephone follow-up. The median overall survival (mOS), duration of drug use, and disease control rate (DCR) of patients were evaluated, and the Cox regression model was used to analyze the risk factors of prognosis. Results: The mOS of 63 patients with HCC administered regorafenib as second-line treatment was 9.6 months, the duration of drug use was 3.8 months, and the DCR was 59% (37/63). Cox multivariate analysis showed that overall survival (OS) was closely related to the level of alpha-fetoprotein (AFP) and treatment method but not to the type of first-line drug. The mOS of patients with AFP ≥400 ng/mL was 7.4 months, which was significantly lower than that of those with AFP <400 ng/mL (12.5 months) (P=0.0052). The mOS of patients treated with regorafenib alone was 6.8 months, which was significantly lower than that of those treated with regorafenib combined with immunotherapy (24.3 months) and intervention therapy (17.5 months) (P<0.0001). The mOS of patients using regorafenib as second-line treatment in the first-line sorafenib group and first-line nonsorafenib group were 9.5 and 9.6 months, respectively (P=0.9766). The grade ≥3 adverse events (AEs) with an incidence of more than 10% included hand-foot syndrome, increased bilirubin, decreased albumin, and elevated transaminase, with incidences of 22%, 14%, 11%, and 10%, respectively. Conclusions: As second-line treatment for patients with HCC with macrovascular invasion and(or) extrahepatic metastasis, regorafenib has definite efficacy and tolerable adverse reactions. It is the preferred drug for the second-line treatment of patients with advanced HCC.