[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

[Genetic and clinical characteristics of single and compound types of patients with long QT syndrome type 3].

Objective: To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3). Methods: This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands. Results: A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion: Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.

[Association of triglyceride glucose index and risk of incident hypertension: a prospective cohort study].

Objective: To explore the relationship between the triglyceride glucose (TyG) index and the risk of developing hypertension among rural Chinese adults. Methods: A prospective cohort study was conducted from 2007 to 2008, involving 20 194 adults selected through random cluster sampling from a rural community in Luoyang City, Henan Province. Follow-ups were carried out in 2013-2014 and 2018-2020. After excluding participants with hypertension at baseline, those with missing TyG index data, individuals who passed away during follow-up, and those with incomplete hypertension status at the second visit, 9 802 participants were included in the analysis. Baseline and follow-up assessments included questionnaire interviews, physical measurements (including blood pressure), and blood sample collection for fasting lipid and glucose levels. Participants were divided into four groups according to TyG index quartiles, and a modified Poisson regression model was utilized to assess the association between TyG index quartiles and hypertension risk. Results: The study cohort comprised 9 802 participants with a median age of 48 (39, 57) years, including 3 803 males (38.80%). Participants were distributed across TyG index quartiles as follows: TyG<8.2 group (2 224 individuals), TyG 8.2-8.5 group (2 653 individuals), TyG 8.6-8.9 (2 441 individuals), and TyG≥9.0 (2 484 individuals). Over a follow-up period of (11.1±1.3) years, 3 378 subjects developed hypertension, resulting in a cumulative incidence of 34.46% (3 378/9 802). The risk of hypertension increased with higher TyG index quartiles (Ptrend<0.05). Compared to the TyG<8.2, the TyG 8.2-8.5 (RR=1.11, 95%CI 1.01-1.22, P=0.023), TyG 8.6-8.9 (RR=1.16, 95%CI 1.06-1.27, P=0.023), and TyG≥9.0 (RR=1.20, 95%CI 1.10-1.31, P=0.023) exhibited increased hypertension risk after adjusting for age, gender, educational level, and other potential confounders. Subgroup analyses based on gender and age at baseline yielded results consistent with the main analysis. Conclusions: The TyG index is positively correlated with the risk of developing hypertension in the rural adult population.

Fusarium diversity associated with diseased cereals in China, with an updated phylogenomic assessment of the genus.

Fusarium species are important cereal pathogens that cause severe production losses to major cereal crops such as maize, rice, and wheat. However, the causal agents of Fusarium diseases on cereals have not been well documented because of the difficulty in species identification and the debates surrounding generic and species concepts. In this study, we used a citizen science initiative to investigate diseased cereal crops (maize, rice, wheat) from 250 locations, covering the major cereal-growing regions in China. A total of 2 020 Fusarium strains were isolated from 315 diseased samples. Employing multi-locus phylogeny and morphological features, the above strains were identified to 43 species, including eight novel species that are described in this paper. A world checklist of cereal-associated Fusarium species is provided, with 39 and 52 new records updated for the world and China, respectively. Notably, 56 % of samples collected in this study were observed to have co-infections of more than one Fusarium species, and the detailed associations are discussed. Following Koch's postulates, 18 species were first confirmed as pathogens of maize stalk rot in this study. Furthermore, a high-confidence species tree was constructed in this study based on 1 001 homologous loci of 228 assembled genomes (40 genomes were sequenced and provided in this study), which supported the "narrow" generic concept of Fusarium (= Gibberella). This study represents one of the most comprehensive surveys of cereal Fusarium diseases to date. It significantly improves our understanding of the global diversity and distribution of cereal-associated Fusarium species, as well as largely clarifies the phylogenetic relationships within the genus. Taxonomic novelties: New species: Fusarium erosum S.L. Han, M.M. Wang & L. Cai, Fusarium fecundum S.L. Han, M.M. Wang & L. Cai, Fusarium jinanense S.L. Han, M.M. Wang & L. Cai, Fusarium mianyangense S.L. Han, M.M. Wang & L. Cai, Fusarium nothincarnatum S.L. Han, M.M. Wang & L. Cai, Fusarium planum S.L. Han, M.M. Wang & L. Cai, Fusarium sanyaense S.L. Han, M.M. Wang & L. Cai, Fusarium weifangense S.L. Han, M.M. Wang & L. Cai. Citation: Han SL, Wang MM, Ma ZY, Raza M, Zhao P, Liang JM, Gao M, Li YJ, Wang JW, Hu DM, Cai L (2023). Fusarium diversity associated with diseased cereals in China, with an updated phylogenomic assessment of the genus. Studies in Mycology 104: 87-148. doi: 10.3114/sim.2022.104.02.

Impact of shift work on dementia: a systematic review and dose-response meta-analysis.

OBJECTIVES: Although shift work has been reported as having a link to dementia, evidence remains inconsistent, and a comprehensive dose-response meta-analysis of the association is still lacking. We therefore conducted this meta-analysis to explore the association between shift work and the risk of dementia. STUDY DESIGN: Systematic review and dose-response meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were systematically searched. Fixed or random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (95% CIs). Generalized least squares regression was used to estimate dose-response associations, and restricted cubic splines were used to examine possible linear or non-linear associations. RESULTS: Five articles (10 studies) with 72,999 participants and 23,067 cases were eventually included in the meta-analysis. The summary RRs and 95% CIs of dementia risk with shift work and night shift work versus daytime work were 1.13 (95% CI: 1.05-1.21, I2 = 46.70%) and 1.13 (95% CI: 1.03-1.24, I2 = 9.20%), respectively. The risk of dementia increased by 1% (RR = 1.01, 95% CI: 1.01-1.02, I2 = 41.3%) with each 1-year increase in the duration of shift work. We found a non-linear dose-response association between the duration of shift work and the risk of dementia (Pnon-linearity = 0.006). Though the shape of the curve was steeper with the duration of shift work <7 years, the increase was more gradual after 7 years. CONCLUSION: Our findings suggest that shift work may be a risk factor for future dementia and that controlling the length of shift work is a feasible measure that may contribute to prevent dementia.

[Self-reported quality of life in patients with coronary heart disease and analysis of the associated factors].

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.

[Analysis on the efficacy of dual vein induction therapy of Ustekinumab in complex perianal fistulizing Crohn's disease].

Objectives: To analyze the efficacy of dual vein induction therapy of Ustekinumab (UST) in complex perianal fistulizing Crohn's disease (PFCD). Methods: Clinical data of patients diagnosed with complex PFCD in the Second Affiliated Hospital of Wenzhou Medical University from January 2022 to March 2023 were retrospectively analyzed. After sufficient single intravenous infusion of UST (6 mg/kg) at week 0 and 8, every patient received single subcutaneous injection of UST 90 mg every 8 weeks for maintenance treatment. At week 8, 16, and 22-26, clinical outcomes of anal fistula were evaluated using perianal disease activity index (PDAI), and overall activity of the patients was evaluated using Harvey Bradshaw index (HBI). At week 22-26, Van Assche Index (VAI) was used to evaluate imaging outcome of anal fistula, and simplified endoscopic score of Crohn's disease (SES-CD) was employed to assess intestinal outcome events. The above indexes were compared in the patients before and after UST treatment. PFCD patients were divided into first-line UST treatment group and non first-line UST treatment group according to whether first-line UST treatment was used, the differences in anal fistula response rate and remission rate, intestinal response rate and remission rate as well as overall activity response rate and remission rate were compared between the two groups. Results: A total of 60 PFCD patients were included, including 46 males and 14 females, aged [M (Q1, Q3)] 25.0 (20.8, 30.0) years old. The clinical response rates of anal fistula [41.7% (25/60), 55.0% (33/60) and 63.3% (38/60), respectively, P=0.056] and the clinical remission rates of anal fistula [21.7% (13/60), 31.7% (19/60) and 43.3% (26/60), respectively, P=0.002] gradually increased at week 8, 16, 22-26. The overall activity response rates [53.3% (32/60), 70.0% (42/60), 83.3% (50/60), respectively, P=0.040] and the overall activity response rates [41.7% (25/60), 61.7% (37/60), 75.0% (45/60), respectively, P=0.001] also gradually increased at week 8, 16, 22-26. At week 22-26, the partial response rate and fistula healing rate of anal fistula imaging were 45.0% (27/60) and 38.3% (23/60), respectively. The endoscopic response rate and endoscopic response rate were 73.7% (44/60) and 45.0% (27/60), respectively. The endoscopic response rate of patients receiving first-line UST treatment [23 males and 8 females, aged 22.0 (21.0, 39.0) years] was higher than that of patients receiving non first-line UST treatment[23 males and 6 females, aged 26.5 (20.0, 30.0) years,87.1% vs 58.6%, P=0.013]. Conclusion: The dual vein induction therapy of UST could effectively improve the clinical efficacy in patients with complex PFCD.

[Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database].

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

Association between insulin-like growth factor-1 and cardiovascular events: a systematic review and dose-response meta-analysis of cohort studies.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) has increasingly been reported as linked to cardiovascular (CV) events; however, reported results have been inconsistent, and no meta-analysis has been undertaken to quantitatively assess this association. METHODS: We searched PubMed, Embase, and Web of Science databases for cohort articles published up to December 1, 2020. Fixed or random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs) of CV events in relation to IGF-1. Restricted cubic splines were used to model the dose-response association. RESULTS: We identified 11 articles (thirteen cohort studies) covering a total of 22,995 participants and 3040 CV events in this meta-analysis. The risk of overall CV events reduced by 16% from the highest to the lowest IGF-1 levels (RR 0.83, 95% CI 0.72-0.95), while the occurrence of CV events reduced by 28% (RR 0.72, 95% CI 0.56-0.92), but not for CV deaths, however (RR 1.00, 95% CI 0.65-1.55). We also found linear associations between IGF-1 levels and CV events. With each per 45 µg/mL IGF-1 increase, the pooled RRs were 0.91 (95% CI 0.86-0.96), 0.91 (95% CI 0.85-0.97) and 0.91 (95% CI 0.84-0.98) for overall CV events, for the occurrence of CV events, and for CV deaths, respectively. CONCLUSIONS: Our findings based on cohort studies support the contention that any increase in IGF-1 is helpful in reducing the overall risk of CV events. As an important biomarker for assessing the likelihood of CV events, IGF-1 appears to offer a promising prognostic approach for aiding prevention.

Development and validation of an individualized nomogram for predicting the high-volume (> 5) central lymph node metastasis in papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. METHODS: We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. RESULTS: The male gender (OR = 2.02, 95% CI 1.46-2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13-2.38), multifocality (OR = 1.87, 95% CI 1.40-2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64-5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40-0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42-0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. CONCLUSION: A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

Global burden of gastric cancer in adolescents and young adults: estimates from GLOBOCAN 2020.

OBJECTIVES: Gastric cancer in adolescents and young adults (GCAYA) has been ignored by both patients and physicians. We examined the disease burden of GCAYA and its secular trends in incidence and mortality. STUDY DESIGN: A comprehensive analysis of the global burden of GCAYA based on data provided by GLOBOCAN 2020. METHODS: Global, regional, sex, and country-specific data of the incidence and mortality of GCAYA were extracted from the GLOBOCAN, the Cancer in Five Continents Plus, and the World Health Organization mortality database, respectively. The associations between the Human Development Index (HDI) and GCAYA burden were also evaluated by Pearson correlation analysis. RESULTS: The global incidence of GCAYA was 0.79 per 100,000, and the corresponding mortality was 0.45 per 100,000 in 2020. The mortality-to-incidence ratio (MIR) was lower in AYA (0.61) than in patients aged 40-64 years (0.65) and patients aged 65 years and older (0.75). The age-standardized incidence rates (ASIR) and age-standardized mortality rates (ASMR) were 0.84 and 0.53 per 100,000, respectively, in women, compared with 0.74 and 0.45 per 100,000, respectively, in men. The majority of new cases (17,934) and deaths (10,360) were estimated to occur in Asia. There has a significant negative correlation between the MIR of GCAYA and HDI level (R2 = 0.2707, P < 0.0001). There was a decreasing trend of incidence and mortality in most countries. CONCLUSIONS: The MIR of GCAYA is lower than that among older patients and exhibit a positive association with socio-economic status. The incidence and mortality of GCAYA show a decreasing trend in most countries.

Cohort study evaluation of New Chinese Diabetes Risk Score: a new non-invasive indicator for predicting type 2 diabetes mellitus.

OBJECTIVES: We aimed to evaluate the predictive power of new Chinese Diabetes Risk Score (NCDRS) for type 2 diabetes mellitus (T2DM) based on a large prospective cohort study. STUDY DESIGN: Large prospective cohort study. METHODS: The baseline examination of the Rural Chinese Cohort Study was initiated in 2007-2008 and followed up in 2013-2014 in Luoyang city, Henan Province of China. The NCDRS included age, sex, body mass index, waist circumference, systolic blood pressure, and family history of diabetes. Cox's proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The predictive capability of NCDRS was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 9,860 participants were included in the present analysis, and during a median follow-up of 6.01 years, 653 of them developed T2DM. In the multivariate models, the risk of T2DM showed a significant increasing trend (Ptrend <0.001): with NCDRS of 18-23, 24-29, and >29 versus <18, the HR was 1.85 (95% CI 1.30-2.64), 2.99 (2.14-4.18), and 3.97 (2.84-5.54), respectively. The predictive value was higher for NCDRS than for the previous Chinese diabetes risk score: AUC 0.675 (95% CI 0.666-0.684) and optimal cut-off of 24 (P < 0.001). Similar results were observed by sex. Especially, the predictive value of NCDRS was high among young people (aged 20-39 years): AUC 0.751 (0.732-0.769). CONCLUSIONS: Our study, based on a large prospective cohort, suggests that NCDRS is a reliable indicator for the identification of T2DM in rural China, especially in younger populations.

[Advance the construction of "health promotion, prevention, diagnosis, control, treatment, rehabilitation" six-in-one working system of chronic obstructive pulmonary disease in China].

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease that seriously threatens people's health. It significantly affects the quality of life of patients and presents an overwhelming economic burden on the governmental perspectives, which makes COPD a major public health issue in China. In this paper, we propose some methods that can help to accelerate the implementation of the Healthy China Strategy and promote the change of people's attitudes towards COPD from disease-centered to health-centered. Those methods are composed of many important aspects including the concepts of"population medicine", the improvement of the national health policy for COPD, the consolidation of the original troika strategy of respiratory disciplines and the high-quality implementation of the three major national projects, aiming to inspire people to participate in the six-in-one work system of dealing with COPD encompassing the health promotion, the prevention, the diagnosis, the control, the treatment, and the rehabilitation.

[The associations of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene polymorphisms with the risk of Crohn's disease in Chinese patients].

Objectives: The present study aimed to investigate the associations of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms with the risk of Crohn's disease (CD) in Chinese patients. Methods: From January 2012 to January 2021, a total of 207 CD patients and 545 age-and gender-matched healthy controls were collected from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. The genotypes of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression analysis was used to analyze the differences of CDKN2B-AS1 polymorphisms between CD patients and healthy controls, as well as their influences on the clinicopathologic characteristics of CD patients. The analyses for linkage disequilibrium and haplotype were further performed by Haploview 4.2 software. Results: The variant genotype (AG+GG) and variant allele (G) of rs1063192 were more prevalent in CD patients than in healthy controls (32.4% vs 24.8%, P=0.036; 18.8% vs 13.6%, P=0.011). The same conclusions were also drawn for homozygous variant genotype (GG) and variant allele (G) of rs10757274 when CD patients were compared with healthy controls (19.8% vs 12.8%, P=0.017; 45.2% vs 38.1%, P=0.012). According to the Montreal Classification Standards, CD patients were stratified into different subgroups. The homozygous variant genotype (GG) and variant allele (G) of rs10757278 were less frequent in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (13.7% vs 29.9%, P=0.015; 37.7% vs 50.4%, P=0.022). However, all the correlations above were no longer significant after Bonferroni's correction (all P>0.05). The polymorphic loci of rs10757274, rs2383207, rs10757278, and rs1333048 were in close linkage disequilibrium with each other in CDKN2B-AS1 gene. Compared with healthy controls, the frequency of haplotype AGAC was decreased in CD patients (1.5% vs 4.5%, χ2=7.61, P=0.006), whereas the frequency of haplotype GGAC was obviously increased in CD patients (3.0% vs 0.6%, χ2=14.25, P<0.001). The stratified analysis further showed that the frequency of haplotype AGAC was higher in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (3.1% vs 0.4%, χ2=5.31, P=0.021). Conclusions: The variations of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) may not independently affect the risk of CD. Among the haplotypes constructed by rs10757274, rs2383207, rs10757278, and rs1333048, the haplotype AGAC may reduce the risk of CD, whereas it may increase the risk of stricturing or penetrating in CD patients. In addition, the haplotype GGAC may increase the risk of CD.

[Multicenter retrospective study of 38 cases with fumarate hydratase deficiency uterine leiomyoma].

Objective: To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma. Methods: The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results: (1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions: FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.

[Association between metabolically healthy obesity and incident risk of stroke in adult aged over 40 from rural Henan province].

Objective: To investigate the association between metabolically healthy obesity and the incident risk of stroke in people aged ≥40 years from rural areas of Henan Province. Methods: During 2007 to 2008, 20 194 residents aged ≥18 years were selected for baseline examination by random cluster sampling and 17 265 participants were followed up during 2013 to 2014. According to the aim of current study, a total of 11 864 eligible subjects were included in this post-hoc analysis. Depending on body mass index and metabolic status, subjects were divided into four groups: metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity. Multivariate logistic regression model was used to analyze the relationship between metabolically healthy obesity and the risk of stroke. Results: The median (Q1, Q3) age of study participants was 54(46, 61) years, and 4 526 participants were men. During the mean follow-up of 6 years, the cumulative incidence of stroke was 7.16%. The incidence of stroke in metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight, and metabolically abnormal obesity were 3.73%, 4.61%, 8.99% and 9.38%, respectively (χ²=117.458, P<0.001). After adjusting possible confounding factors, compared with metabolically healthy normal weight, the risk of stroke was significantly increased in the metabolically healthy obesity group, metabolically abnormal normal weight group and metabolically abnormal obesity group with the odds ratio (OR) and 95% confidence interval (CI) of 1.52(1.10-2.12), 2.11(1.61-2.77) and 2.78(2.18-3.55), respectively. Stratified analysis showed that the risk of stroke was significantly higher in metabolically healthy obesity people aged 40-59 years compared with metabolically healthy normal weight group (OR=2.12, 95%CI: 1.36-3.30). Conclusion: Metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity are positively associated with the risk of stroke.

[Neurofibromatosis type 1 initially presented with glaucoma in the Department of Ophthalmology: a case report].

An eleven-year-old boy visited the Department of Ophthalmology due to visual acuity loss accompanied by high intraocular tension in the left eye for one year. Besides glaucoma, the typical ocular manifestations of neurofibromatosis type 1 such as bilateral Lisch nodules of the iris, multiple patchy choroidal nodules and retinal microvascular abnormalities were identified, and Cafe-au-lait macules appeared on the body skin. Based on the medical history, clinical presentation and auxiliary examination results, the diagnosis of neurofibromatosis type 1 with secondary glaucoma in the left eye was confirmed.

Tibiofemoral articular cartilage composition differs based on serum biochemical profiles following anterior cruciate ligament reconstruction.

OBJECTIVE: Biochemical joint changes contribute to posttraumatic osteoarthritis (PTOA) development following anterior cruciate ligament reconstruction (ACLR). The purpose of this longitudinal cohort study was to compare tibiofemoral cartilage composition between ACLR patients with different serum biochemical profiles. We hypothesized that profiles of increased inflammation (monocyte chemoattractant protein-1 [MCP-1]), type-II collagen turnover (type-II collagen breakdown [C2C]:synthesis [CPII]), matrix degradation (matrix metalloproteinase-3 [MMP-3] and cartilage oligomeric matrix protein [COMP]) preoperatively to 6-months post-ACLR would be associated with greater tibiofemoral cartilage T1ρ relaxation times 12-months post-ACLR. DESIGN: Serum was collected from 24 patients (46% female, 22.1 ± 4.2 years old, 24.0 ± 2.6 kg/m2 body mass index [BMI]) preoperatively (6.4 ± 3.6 days post injury) and 6-months post-ACLR. T1ρ Magnetic Resonance Imaging (MRI) was collected for medial and lateral tibiofemoral articular cartilage at 12-months post-ACLR. A k-means cluster analysis was used to identify profiles based on biomarker changes over time and T1ρ relaxation times were compared between cluster groups controlling for sex, age, BMI, concomitant injury (either meniscal or chondral pathology), and Marx Score. RESULTS: One cluster exhibited increases in MCP-1 and COMP while the other demonstrated decreases in MCP-1 and COMP preoperatively to 6-months post-ACLR. The cluster group with increases in MCP-1 and COMP demonstrated greater lateral tibial (adjusted mean difference = 3.88, 95% confidence intervals [1.97-5.78]) and femoral (adjusted mean difference = 12.71, 95% confidence intervals [0.41-23.81]) T1ρ relaxation times. CONCLUSION: Profiles of increased serum levels of inflammation and matrix degradation markers preoperatively to 6-months post-ACLR are associated with MRI changes consistent with lesser lateral tibiofemoral cartilage proteoglycan density 12-months post-ACLR.

Inter-relationship of risk factors and pathways associated with chronic kidney disease in patients with type 2 diabetes mellitus: a structural equation modelling analysis.

OBJECTIVES: Diabetes mellitus is the most common cause of chronic kidney disease (CKD); however, the inter-relationships and pathogenetic mechanisms among risk factors are still largely unknown. Structural equation modelling (SEM) was applied to test a hypothesis of causal pathways related to CKD in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: This is a prospective observational study. METHODS: A total of 3395 patients with T2DM were enrolled in this study. A hypothesised SEM was applied to assess associations among demographic data, diabetic self-management behaviours, diabetes control, lifestyle, psycho-social, chronic inflammation factors, anthropometric and metabolic variables simultaneously and the risk of CKD. RESULTS: Demographic data (including education, marital status and mini-mental state examination score) (-0.075), white blood cell count (0.084), high blood pressure (0.144), World Health Organisation (WHO) 5 well-being index (-0.082), diabetes control (0.099), triglyceride (0.091) and uric acid (0.282) levels had direct effects on the risk of CKD. The final model could explain 26% of the variability in baseline CKD status. In addition, the same direct and specific indirect factors at baseline CKD status analysis contributed to the risk of CKD at the 12-month follow-up. The final model could explain 31% of the variability in the risk of CKD at the 12-month follow-up. CONCLUSIONS: This study investigates associations between factors obtained from real-world daily practice and CKD status simultaneously and delineates the potential pathways and inter-relationships of the risk factors that contribute to the development of CKD in patients with T2DM.

Adherence to antihypertensive medications for secondary prevention of cardiovascular disease events: a dose-response meta-analysis.

OBJECTIVES: The aim of the study was to explore the association between adherence to antihypertensive medications (AHMs) and the risk of recurrence of cardiovascular disease (CVD) events in patients with a history of CVD events from cohort studies. STUDY DESIGN: This is a dose-response meta-analysis. METHODS: PubMed and Embase databases were searched up to March 4, 2021, to identify English-language reports of cohort studies that assessed the association of AHM adherence with risk of recurrence of CVD events. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by using a fixed- or random-effects model. Restricted cubic splines were used to evaluate the possible linear or non-linear association. RESULTS: We included nine cohort studies (54,349 patients) in the present meta-analysis. The pooled RR of CVD events was 0.66 (95% CI, 0.54-0.78) for the highest versus lowest AHM adherence category. We did not find any evidence of non-linearity association between AHM adherence and risk of CVD events (Pnon-linearity = 0.534); for patients with a history of CVD events, the risk of CVD events was reduced by 9% for each 20% increase in AHM adherence (RR, 0.91; 95% CI, 0.85-0.97). The results of sensitivity analysis and subgroup analysis were virtually unchanged. CONCLUSIONS: The high level of adherence to AHM is an effective strategy for preventing recurrence of CVD events. Patients with a history of CVD events should adhere to AHM.