Associations between serum uric acid and breast cancer incidence: A systematic review and meta-analysis.

BACKGROUND: Serum uric acid (SUA) may be involved in the development of cancer by inhibiting oxidative stress, but its relationship with breast cancer remains unclear. METHODS: The PubMed, Embase, and Web of Science databases were searched systematically for studies on SUA levels in women with breast cancer and the effect of SUA levels on the risk of breast cancer. The Newcastle‒Ottawa Quality Assessment Scale (NOS) was used to assess the quality of all relevant studies included. RESULTS: A total of 19 studies were included, including 75,827 women with breast cancer and 508,528 healthy controls. A meta-analysis found that SUA levels were negatively correlated with breast cancer risk in women (HR = 0.94, 95% CI: 0.89 - 0.99, p = 0.003). SUA levels in female breast cancer patients were not significantly different from those in healthy controls (SMD = 0.49, 95% CI = -0.09 - 1.08, p = 0.10), while SUA levels were increased in female breast cancer patients in articles published after 2010, SUA concentration detected by spectrophotometry, and non-Asian populations, regardless of menopausal state and treatment state. CONCLUSION: High levels of SUA may reduce the risk of breast cancer in women, suggesting that SUA was a protective factor in women.

Potential correlations between asymmetric disruption of functional connectivity and metabolism in major depressive disorder.

OBJECTIVE: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. METHOD: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. RESULTS: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.

Machine learning-based diagnostic model for preoperative differentiation between xanthogranulomatous cholecystitis and gallbladder carcinoma: a multicenter retrospective cohort study.

Background: Xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma (GBC) share similar imaging and serological profiles, posing significant challenges in accurate preoperative diagnosis. This study aimed to identify reliable indicators and develop a predictive model to differentiate between XGC and GBC. Methods: This retrospective study involved 436 patients from Zhejiang Provincial People's Hospital and The Affiliated Lihuili Hospital of Ningbo University. Comprehensive preoperative imaging, including ultrasound, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and blood tests, were analyzed. Machine learning (Random Forest method) was employed for variable selection, and a multivariate logistic regression analysis was used to construct a nomogram for predicting GBC. Statistical analyses were performed using SPSS and RStudio software. Results: The study identified gender, Murphy's sign, absolute neutrophil count, glutamyl transpeptidase level, carcinoembryonic antigen level, and comprehensive imaging diagnosis as potential risk factors for GBC. A nomogram incorporating these factors demonstrated high predictive accuracy for GBC, outperforming individual or combined traditional diagnostic methods. External validation of the nomogram showed consistent results. Conclusion: The study successfully developed a predictive nomogram for distinguishing GBC from XGC with high accuracy. This model, integrating multiple clinical and imaging indicators, offers a valuable tool for clinicians in making informed diagnostic decisions. The findings advocate for the use of comprehensive preoperative evaluations combined with advanced analytical tools to improve diagnostic accuracy in complex medical conditions.

Role of NF-κB Signaling Pathway in "Reflux Esophagitis-esophageal Cancer" and Traditional Chinese Medicine Intervention：A Review / 中国实验方剂学杂志

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise， and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa， causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue， which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B （NF-κB） signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation， autophagy， apoptosis， and inflammatory response of esophageal epithelial cells and tumor cells， accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently， there is no specific treatment for reflux esophagitis and esophageal cancer， and large side effects often appear. Therefore， finding a promising and safe drug remains a top priority. In recent years， traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway， and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， but there is a lack of comprehensive and systematic elaboration. Therefore， this paper summarized the relevant studies in recent years， analyzed the relationship among NF-κB signaling pathway， reflux esophagitis， esophageal cancer， and transformation from inflammation to cancer， and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

Research progress on the mechanism of traditional Chinese medicine intervening in esophageal cancer by microRNA regulation / 中国药房

Esophageal cancer （EC） is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA （miRNA） is an important regulator in tumor occurrence and development， and can participate in malignant biological behaviors such as tumor cell proliferation， invasion， metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects， wide range of effects， and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine （including curcumin， Tussilago farfara polysaccharides， Atractylodes macrocephala polysaccharides and ophiopogonin B） and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p （miR-532-3p）， miR-551b-3p， miR-99a， miR-34a， miR-199a-3p and miR-377； and the active ingredients/parts of traditional Chinese medicine （including chrysin and Actinidia arguta extract）， and Chinese herbal formulas （including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction） could down-regulate the expressions of miRNAs such as miR-199a-3p， miR-451 and miR-21， which could regulate the expressions of signaling pathways （phosphoinositide 3-kinase/protein kinase B， etc.） or their downstream protein（zinc-finger and homeobox protein 1， etc.） or enzymes（thymidine kinase-1， etc.）， inhibit the proliferation， invasion and metastasis of EC cells and induce apoptosis， thereby ultimately achieving the purpose of preventing the disease from aggravating.

Progress and prospect of inhaled biological agents in asthma / 中国临床药理学与治疗学

More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis.

OBJECTIVE: To investigate the effect of the TLR4/MyD88/NF-κB (Toll-like receptor 4/myeloid differentiation factor/nuclear factor kappa B) signalling pathway on the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis. METHODS: A mouse model of sepsis was established by classical caecal ligation and perforation. Forty-four SPF C57BL/6 mice were randomly divided into the following four groups with 11 mice in each group: the control group (Con group), ulinastatin group (Uti group), Uti + LPS (lipopolysaccharide, LPS) group (Uti + LPS group) and LPS group. Mice in the Con group and Uti group received saline or ulinastatin injected 2 h after modelling; Mice in the Uti + LPS group received LPS injected 0 h after modelling, other procedures were the same as in the Uti group; Mice in the LPS group received LPS only. At 48 h after surgery, the levels of TNF-α (tumour necrosis factor-α, TNF-α), IL-6 (interleukin-6, IL-6) and IL-1ß (interleukin-1ß, IL-1ß) in vein, and the expression of TLR4, MyD88 and NF-κB mRNA in small intestinal mucosa tissues using ELISA and RT‒PCR. RESULTS: The pathological specimens showed increased inflammatory injury in the Con and LPS groups, while these injuries and changes improved in the Uti group. The scores of intestinal mucosal injury at 48 h of Uti injection were significantly lower than those of the Con group (P < 0.001), while the scores of intestinal mucosal injury of Uti + LPS were significantly higher than those of the Uti group (P = 0.044). The expression of TNF-α, IL-6 and IL-1ß in the Uti decreased significantly at 48 h after surgery than that in the Con group (P = 0.001, P = 0.014, P = 0.004), while the expression of TNF-α, IL-6 and IL-1ß in the Uti + LPS group increased significantly after surgery than that in the Uti group (P = 0.026, P = 0.040, P = 0.039). The expression of TLR4, MyD88 and NF-κB mRNA in the Uti group decreased significantly compared with that in the Con group (P = 0.001, P = 0.021, P = 0.007), while the expression of TLR4, MyD88 and NF-κB mRNA in the Uti + LPS group was higher than that in the Uti group (P = 0.023, P = 0.040, P = 0.045). CONCLUSION: These findings indicate that the protective effect of ulinastatin on the intestinal mucosal barrier against sepsis may be mediated through the TLR4/MyD88/NF-κB pathway.

Unipolar and bipolar electrograms to predict successful ablation site of premature ventricular contractions originating from the free wall of the tricuspid annulus.

INTRODUCTION: This study aimed to identify the characteristics of unipolar and bipolar electrogram (UniEGM and BiEGM) in guiding successful ablation of premature ventricular contractions (PVCs) originating from the free wall of the ventricular aspect of the tricuspid annulus (TA). We hypothesized that the negative concordance pattern (NCP) on the onset of UniEGM and BiEGM, together with the least value of the difference between the earliest BiEGM and UniEGM dV/dTmax, might improve the accuracy of conventional mapping. METHODS AND RESULTS: Thirty consecutive patients who underwent successful catheter ablation from February 2018 to July 2021 were retrospectively analyzed. The BiEGM and UniEGM for successful ablation sites were compared with those for non-successful ablation sites. Among the 30 patients, 30 successful and 26 nonsuccessful ablation sites were compared. The earliest activation time of the BiEGM (BiEGMoneset-QRS) was 25 ± 6 ms for the successful ablation sites and 21 ± 6 ms for the nonsuccessful ablation sites (p = .47). The value of the difference in the earliest BiEGM and UniEGM dV/dTmax differed between successful and nonsuccessful ablation sites (6.4 ± 3.6 ms vs. 10.4 ± 6.8 ms). NCP was observed at 90.0% and 42.3% of the successful and nonsuccessful ablation sites, respectively. Alignment of NCP and BiEGMonset-UniEGM ≤6 ms was applied as the mapping criterion for successful PVC suppression (73.1% sensitivity and 87.7% specificity). The area under the receiver-operating characteristic curve for this cutoff was 0.85. CONCLUSION: Mapping based on an NCP at the onset of the BiEGM and UniEGM and the least difference value of the earliest BiEGM and UniEGM dV/dTmax had an excellent predictive value for successful ablation. These strategies may reduce the number of radiofrequency catheter ablation (RFCA) applications for free-wall tricuspid annular PVCs.

Utility of Ultrasonography for Diagnosing and Differentiating Periapical Granuloma from Radicular Cyst.

RATIONALE AND OBJECTIVES: This study aimed to investigate the reliability and accuracy of high-resolution ultrasonography (US) for diagnosing periapical lesions and differentiating radicular cysts from granulomas. MATERIALS AND METHODS: This study included 109 teeth with periapical lesions of endodontic origin from 109 patients scheduled for apical microsurgery. Ultrasonic outcomes were analyzed and categorized after thorough clinical and radiographic examinations using US. B-mode US images reflected the echotexture, echogenicity, and lesion margin, while color Doppler US assessed the presence and features of blood flow of interested areas. Pathological tissue samples were obtained during apical microsurgery and subjected to histopathological examination. Fleiss' κ was used to measure interobserver reliability. Statistical analyses were performed to assess the diagnostic validity and the overall agreement between US and histological findings. The reliability of US compared to histopathological examinations was assessed based on Cohen's κ. RESULTS: The percent accuracy of US for diagnosing cysts, granulomas, and cysts with infection based on histopathological findings was 89.9%, 89.0%, and 97.2%, respectively. The sensitivity of US diagnoses was 95.1% for cysts, 84.1% for granulomas, and 80.0% for cysts with infection. The specificity of US diagnoses was 86.8% for cysts, 95.7% for granulomas, and 98.1% for cysts with infection. The reliability for US compared to histopathological examinations was good (κ = 0.779). CONCLUSION: The echotexture characteristics of lesions in US images correlated with their histopathological features. US can provide accurate information on the nature of periapical lesions based on the echotexture of their contents and the presence of vascularity. It can help improve clinical diagnosis and avoid overtreatment of patients with apical periodontitis.

Impact of long-term fertilization on phosphorus fractions and manganese oxide with their interactions in paddy soil aggregates.

One under-studied microelement, manganese (Mn), due to its potential to considerably interact, and limit labile, and moderately-labile soil phosphorus (P) pools, was studied in Nanchang (NC), and Qiyang (QY) under paddy conditions. The Hedley's P sequential fractionation procedure was utilized to extract, and quantify various P fractions at both surface (0-20 cm) and subsurface (20-40 cm) layers. Unfertilized control (CK), nitrogen, phosphorus, and potassium (NPK), and NPK amended with animal manure (NPKM) were used as treatments. From both sites, the manure amended fertilizer (NPKM) compared to chemical NPK formed higher proportions of macro-aggregates (>2 and 2-0.25 mm) in both layers. Total P (TP) values of 842.1 (>2 mm), and 744.4 mg kg-1 (2-0.25 mm) from NC, and QY, respectively were accumulated by NPKM compared to NPK, and CK. Total P values of 806.4, and 350.4 mg kg-1 in the >2 mm aggregate size, respectively for NC, and QY were observed in the subsurface layer. Inorganic moderately labile P (NaOH-Pi) was the dominant fraction under all fertilizer treatments. Concentrations of 232.3 (<0.053 mm), and 202.1 mg kg-1 (0.25-0.053 mm) of NaOH-Pi were accumulated by NPKM, respectively for NC, and QY in the surface layer. In the subsurface layer, concentrations of NaOH-Pi (217.5 mg kg-1; <0.053 mm) from NC, and residual-P (57.3 mg kg-1; >2 mm) from QY were accumulated by NPKM. Similarly, NPKM in contrast to NPK contributed higher Mehlich-3 manganese (M3-Mn) oxide in all aggregate sizes from both sites. Generally, macro-aggregates contributed higher TP, fractions of P, and M3-Mn oxide than micro-aggregates. There was a positive relationship between P pools and M3-Mn oxide at both sites. Additions of animal manure were associated with increased P fractions, and Mn oxides in the paddy soil aggregates, which raises environmental concern.

Research progress on cardiovascular effects of traffic-related air pollution and noise: Evidence from population-based and mechanism studies / 环境与职业医学

Traffic-related air pollution and noise are becoming increasingly prominent issues in the context of urbanization, both of which are modifiable environmental risk factors for cardiovascular diseases. Those two kinds of traffic-related pollution may have combined effects on the cardiovascular system of human beings, but the biological mechanisms by which they may interact have not been elucidated yet. Thus, we reviewed the research progress based on published population-based and mechanism studies from five aspects, including oxidative stress, inflammatory response, nervous system activation and stress hormones, coagulation dysfunction, and endothelial dysfunction, providing indications for possible common biological pathways. Future studies can construct co-exposure scenarios for traffic-related air pollution and noise to explore their common biological mechanisms in the cardiovascular system by examining the reviewed pathways to provide a scientific basis for the protection of susceptible populations. In addition, the effect modification by individual characteristics and underlying diseases may merit further exploration.

Relationship between reduction of urban PM2.5 and mental health of middle-aged and elderly people after China's Air Pollution Prevention and Control Action Plan / 环境与职业医学

Background Epidemiological evidence indicates an association of particulate matter with depression and cognitive performance. From 2013 to 2017, China implemented the Air Pollution Prevention and Control Action Plan to reduce particulate matter concentration. There are few studies on the relationship between the decrease of particulate matter concentration and the improvement of mental health in middle-aged and elderly people. Objective To analyze the relationship between the decrease of city-level particulate matter concentration and the improvement of depression and cognitive function in the middle-aged and elderly population after the implementation of the Air Pollution Prevention and Control Action Plan. Methods Using the China Health and Retirement Longitudinal Study (CHARLS) data in 2011 and 2018, this study applied longitudinal data clustering technology to group cities based on the actual response of each city to the policy (the dynamic change trajectory of PM2.5 in each city during the study period); the higher the degree of response, the greater the reduction of PM2.5 concentration in the city. We assigned participants to three groups with different degrees of response to the policy, including low-response group A as the control group, medium-response intervention group B, and high-response intervention group C. A difference-in-differences (DID) model was used to estimate the influence of PM2.5 decline on the depression and cognitive function among middle-aged and elderly people in China by considering potential individual and city-level time-varying confounders. Depression was measured using the 10-item Center for the Epidemiological Studies of Depression Scale (CES-D10) (10 questions, total score range 0-30) with higher score representing higher severity of depression. Cognitive function was evaluated with reference to the international cognitive function test questionnaire for the middle-aged and the elderly which was further categorized into two dimensions of memory and cognitive status and included 31 questions with a score range of 0-31; the higher the score, the better the cognitive function. Samples with relatively complete outcomes were selected for analysis, including 10729 people in depression analysis and 4510 people in cognitive analysis. Results The longitudinal clustering results indicated that the urban groups with the highest decline of PM2.5 concentrations (high-response group C) had the highest baseline PM2.5 concentrations, mainly in Beijing-Tianjin-Hebei region, Chengdu-Chongqing metropolitan area, and Wuhan metropolitan area. In 2011, no significant differences were observed in depression and cognitive function among the three groups of middle-aged and elderly populations (Kruskal Wallis test: Pdepression=0.864, Pcognition=0.239). Significant differences were found in depression and cognitive function in both low-response group A and medium-response group B in 2018 compared to 2011 (paired Wilcox test, all P<0.001). However, in the high-response group C, there was no significant difference in depression in 2018 compared to 2011 (P=0.195), while a significant difference was detected in cognitive function (P=0.006). As PM2.5 concentrations decreased, the DID model showed that the depression of the middle-aged and elderly people in the high-response group C decreased by 7.55% (95%CI: 2.83%-12.03%), and the cognitive function improved by 2.70% (95%CI: 0.25%-5.22%) compared with the low-response group A. However, no intervention effect was observed in group B with moderate response level compared with group A with low response level. Conclusion After the implementation of the Air Pollution Prevention and Control Action Plan policy, the decrease of PM2.5 concentration has an ameliorative effect on the depression and cognitive function of middle-aged and elderly people in China. Given the aging population and the increasing burden of mental-related diseases in China, the promotion of environmental air pollution control has important public health implications.

A consensus on the management of allergy in kindergartens and primary schools / 中国学校卫生

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Diagnosis of a case with Hermansky-Pudlak syndrome type 5 through high-throughput sequencing and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with Hermansky-Pudlak syndrome type 5 (HPS-5).@*METHODS@#A child with HPS-5 who had attended the Children's Hospital Affiliated to Shandong University on October 3, 2019 was selected as the study subject. Clinical data of the child were collected. Genetic variant was analyzed through high-throughput sequencing. A literature review was also carried out.@*RESULTS@#The child, a 1-year-and-5-month-old girl, had nystagmus since childhood, lost of retinal pigmentation by fundus examination and easy bruising. High-throughput sequencing revealed that she has harbored compound heterozygous variants of the HPS5 gene, namely c.1562_1563delAA (p.F521Sfs*27) and c.1404C>A (p.C468X), which were inherited from his father and mother, respectively. Based on the guidelines from the American College for Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS+PM2_Supporting+PM3+PP4). Among 18 previously reported HPS-5 patients, all had had eye problems, and most of them had tendency for bleeding. Eight cases had carried compound heterozygous variants of the HPS5 gene, 8 carried homozygous variants, 2 carried double homozygous variants, and most of them were null mutations.@*CONCLUSION@#The c.1562_1563delAA(p.F521Sfs*27) and c.1404C>A (p.C468X) compound heterozygous variants of the HPS5 gene probably underlay the HPS-5 in this child. High-throughput sequencing has provided an important tool for the diagnosis. HSP-5 patients usually have typical ocular albinism and/or oculocutaneous albinism and tendency of bleeding, which are commonly caused by compound heterozygous and homozygous variants of the HPS5 gene, though serious complications have been rare.

Associations between glycated hemoglobin and glucose indicators in adults in areas at different altitude in China / 中华流行病学杂志

Objective: To explore the associations of glycated hemoglobin (HbA1c) with FPG and oral glucose tolerance test 2-hour (OGTT-2 h) in areas at different altitude in China. Methods: Subjects who participated in 2018-2019 China Chronic Disease and Risk Factor Surveillance and had no prior type 2 diabetes diagnosis were included. Subsequently, they were categorized into three groups based on altitude of living area (<2 000, 2 000- and ≥3 000 m). With adjustment for intracluster correlation, multivariable linear regression analysis was performed to evaluate the associations of HbA1c with FPG and OGTT-2 h in the context of HbA1c was normal (<5.7%) or abnormal (≥5.7%). Furthermore, the shape of relationships between HbA1c and glucose indicators was examined using restricted cubic spline. Finally, receiver operating characteristic curve was used to evaluate the diagnostic performance of HbA1c for diabetes. Results: A total of 157 277 subjects were included in the analysis. While FPG and OGTT-2 h levels gradually decreased with increase of altitude, HbA1c level was similar among the three groups. When HbA1c was <5.7%, its association with FPG and OGTT-2 h was weak and no obvious difference was observed among the three groups. When HbA1c was ≥5.7%, the FPG and OGTT-2 h increased by 15.45% (95%CI:14.71%- 16.18%) and 24.54% (95%CI:23.18%-25.91%) respectively per one standard deviation increase in HbA1c in group in area at altitude <2 000 m. However, the FPG and OGTT-2 h increased by 13.08% (95%CI:10.46%-15.76%) and 21.72% (95%CI:16.39%-27.31%), respectively, in group in area at altitude 2 000- m, and increased by 11.41% (95%CI:9.32%-13.53%) and 20.03% (95%CI:15.38%- 24.86%), respectively, in group of altitude ≥3 000 m. The restricted cubic spline indicated that the curve showing the association of HbA1c with FPG and OGTT-2 h was flat when HbA1c was <5.7%, but showed a positive linear relationship when HbA1c was ≥5.7%. The area under curve for detecting diabetes was 0.808 (95%CI:0.803-0.812) in group of altitude <2 000 m and 0.728 (95%CI:0.660-0.796, P=0.022) in group of altitude ≥3 000 m. The relevant optimal cutoff value of HbA1c was 5.7%, with a sensitivity of 65.4% and a specificity of 83.0%, and 6.0%, with a sensitivity of 48.3% and a specificity of 93.7%, respectively. Conclusions: When HbA1c was ≥5.7%, the association between HbA1c and glucose indicators became weaker as the increase of altitude. In the area at altitude ≥3 000 m, it may not be appropriate to use HbA1c in the diagnosis of diabetes.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Content determination of seven active components of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats by UPLC-MS/MS / 中国中药杂志

In the present study, the contents of seven active components [genipinic acid(GA), protocatechuic acid(PCA), neochlorogenic acid(NCA), chlorogenic acid(CA), cryptochlorogenic acid(CCA),(+)-pinoresinol di-O-β-D-glucopyranosid(PDG), and(+)-pinoresinol 4'-O-β-D-glucopyranoside(PG)] of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats(SHR) were simultaneously determined by ultra-high liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The qualified SHR models were selected. The primary aortic endothelial cells(VECs) of rats were separated and cultured by ligation and adherence, followed by subculture. After successful identification, an UPLC-MS/MS method for simultaneously determining the contents of GA, PCA, NCA, CA, CCA, PDG, PG in seven components of Eucommiae Cortex in VECs was established, including specificity, linearity, matrix effect, recovery, accuracy, precision and stability. The established method had the lo-west limit of quantification of 0.97-4.95 μg·L~(-1), accuracy of 87.26%-109.6%, extraction recovery of 89.23%-105.3%, matrix effect of 85.86%-106.2%, and stability of 86.00%-112.5%. Therefore, the established accurate UPLC-MS/MS method could rapidly and simultaneously determine the contents of the seven active components of Eucommiae Cortex in VECs of SHRs, which provided a refe-rence for the study of cellular pharmacokinetics of active components of Eucommiae Cortex extract.

Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor / 中国医学科学院学报

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 μmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.

Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China.@*METHODS@#A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses.@*RESULTS@#The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001).@*CONCLUSION@#Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.

A cohort study of vincristine-induced peripheral neuropathy in children / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.