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Rui Bai,1,2 Yuhang Sui,1,2 Tianqi Lu,1,2 Hua Chen,1,2 Gang Wang,1,2 Rui Kong,1,2 Hongtao Tan,1,2 Yongwei Wang,1,2 Guanqun Li,1,2 Bei Sun1,2 1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Guanqun Li; Bei Sun, Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, People’s Republic of China, Email liguanqun@hrbmu.edu.cn; sunbei70@hrbmu.edu.cnPurpose: The effects of the step-jump approach on the survival and prognosis of infected pancreatic necrosis (IPN) patients have not yet been determined.Patients and Methods: Between November 2018 and June 2023, 188 patients were included in this study. There were 144 patients in the step-up group (the SU group) and 44 in the step-jump group (the SJ group). In the SU group, patients successfully treated with percutaneous catheter drainage (PCD) alone were classified into the SU-1 group (n=101), while those requiring additional surgery after PCD were categorized into the SU-2 group (n=43). In the SJ group, patients who underwent minimally invasive necrosectomy (MIN) without PCD were assigned to the SJ-1 group (n=34), whereas those who initially underwent PCD followed by immediate open surgery were placed in the SJ-2 group (n=10). Propensity score matching (PSM) was used to mitigate bias.Results: After PSM, a total of 34 pairs were successfully matched. A comparison of the SU group with the SJ-1 group (upfront MIN without PCD) revealed similar mortality rates (P=0.239); however, the incidences of multiple drug-resistant organisms (MDROs) (P=0.029) and surgical complications (P< 0.001) were significantly lower in the SJ-1 group. After comparing the SU-2 and SJ-2 groups (patients who underwent direct open necrosectomy without MIN after PCD failure), the incidences of surgical complications and MDRO in the SJ-2 group were significantly lower (P< 0.05).Conclusion: Compared with the step-up approach, the step-jump approach is safer and more effective and can significantly reduce the incidence of MDRO and surgical complications.Keywords: infected pancreatic necrosis, step-up approach, step-jump approach, propensity score match

Ruojing Bai, Jun Guo Department of Geriatric Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Jun Guo, Department of Geriatric Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China, Email junguo_med@tsinghua.edu.cnAbstract: Klebsiella pneumoniae (K. pneumoniae), a significant contributor to the global challenge of antibiotic resistance, is not only a ubiquitous component of the human microbiome but also a potent pathogen capable of causing a spectrum of diseases. This review provides a thorough analysis of the intricate interactions between K. pneumoniae and the human immune system, elucidating its substantial impact on metabolic processes. We explore the mechanisms employed by K. pneumoniae to evade and manipulate immune responses, including molecular mimicry, immune modulation, and biofilm formation. The review further investigates the bacterium’s influence on metabolic pathways, particularly glycolysis, highlighting how these interactions exacerbate disease severity. The emergence of multidrug-resistant and extremely drug-resistant strains within the Enterobacteriaceae family has heightened the public health crisis, underscoring the urgency for comprehensive research. We investigate the roles of the host’s complement system, autophagy, cell death mechanisms, and various cytokines in combating K. pneumoniae infections, shedding light on areas that warrant further academic investigation. Additionally, the review discusses the challenges posed by K1- and K2-capsule polysaccharides in vaccine development due to their complex molecular structures and adhesive properties. Acknowledging the limited availability of effective antimicrobials, this review advocates for exploring alternative approaches such as immunotherapeutics, vaccinations, and phage therapy. We consolidate current knowledge on K. pneumoniae, covering classical and non-classical subtypes, antimicrobial resistance-mediated genes, virulence factors, and epidemiological trends in isolation and antibiotic resistance rates. This comprehensive review not only advances our understanding of K. pneumoniae but also underscores the imperative for ongoing research and collaborative efforts to develop new prevention and treatment strategies against this formidable pathogen.Keywords: Klebsiella pneumoniae, complement system, pathogenic mechanism, drug-resistant, treatment strategy

Ruifeng Bai,1 Jianqiu Pei,1 Shengqiang Pei,1 Xiangfeng Cong,1 Jerold Chun,2 Fang Wang,1,3,4 Xi Chen1,3 1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Neuroscience Drug Discovery, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; 3Diagnostic Laboratory Service, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Fuwai Yunnan Cardiovascular Hospital, Kunming, People’s Republic of ChinaCorrespondence: Xi Chen; Fang Wang, Email chenxifw@pumc.edu.cn; fray.163@163.comBackground: Increased endothelial permeability of pulmonary vessels is a primary pathological characteristic of septic acute lung injury (ALI). Previously, elevated lysophosphatidic acid (LPA) levels and LPA2 (an LPA receptor) expression have been found in the peripheral blood and lungs of septic mice, respectively. However, the specific role of LPA2 in septic ALI remains unclear.Methods: A lipopolysaccharide (LPS)-induced model of sepsis was established in wild-type (WT) and global LPA2 knockout (Lpar2−/−) mice. We examined mortality, lung injury, assessed endothelial permeability through Evans blue dye (EBD) assay in vivo, and transendothelial electrical resistance (TEER) of mouse lung microvascular endothelial cells (MLMECs) in vitro. Enzyme-linked immunosorbent assay (ELISA), histopathological, immunofluorescence, immunohistochemistry, and Western blot were employed to investigate the role of LPA2 in septic ALI.Results: Lpar2 deficiency increased vascular endothelial permeability, impaired lung injury, and increased mortality. Histological examination revealed aggravated inflammation, edema, hemorrhage and alveolar septal thickening in the lungs of septic Lpar2−/− mice. In vitro, loss of Lpar2 resulted in increased permeability of MLMECs. Pharmacological activation of LPA2 by the agonist DBIBB led to significantly reduced inflammation, edema and hemorrhage, as well as increased expression of the vascular endothelial tight junction (TJ) protein zonula occludens-1 (ZO-1) and claudin-5, as well as the adheren junction (AJ) protein VE-cadherin. Moreover, DBIBB treatment was found to alleviate mortality by protecting against vascular endothelial permeability. Mechanistically, we demonstrated that vascular endothelial permeability was alleviated through LPA-LPA2 signaling via the PLC-PKC-FAK pathway.Conclusion: These data provide a novel mechanism of endothelial barrier protection via PLC-PKC-FAK pathway and suggest that LPA2 may contribute to the therapeutic effects of septic ALI.Keywords: septic ALI, LPA, vascular endothelial permeability, LPA2, lung microvascular endothelial cells

Shiyun Lv,1,&ast; Lijun Sun,1,&ast; Tongzeng Li,1,&ast; Ruojing Bai,1 Man Dai,2,3 Ran Wang,1 Yuanyi Zhai,1 Wei Hua,1 Aixin Li,1 Ruolei Xin,2 Lili Dai1 1Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Institute for STD/AIDS Prevention and Treatment, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 3School of Public Health, Chinese Medical University, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Dai, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China, Tel +86 10 83911069, Email lilydaier@ccmu.edu.cn Ruolei Xin, Institute for STD/AIDS Prevention and Treatment, Beijing Center for Disease Prevention and Control, Beijing, 100013, People’s Republic of China, Tel +86 10 64407364, Email xinruolei@sina.comObjective: To analyze the antiretroviral resistance in people living with HIV (PLWH) who developed low-level viremia (LLV) during antiretroviral therapy (ART) via sequencing of their HIV-1 proviral DNA and RNA and comparisons of their proviral DNA genotyping data with their past and synchronous RNA genotyping data.Patients and Methods: PLWH with LLV while receiving ART for 6 months or longer from January 2020 to September 2021 were included. HIV-1 proviral DNA and RNA were extracted from white-blood cells and concentrated plasma by ultracentrifugation, respectively, and HIV-1 pol gene fragments were amplified and sequenced. The concordance in the detection of resistance-associated mutations (RAMs) were examined between proviral DNA vs past RNA genotyping and proviral DNA vs synchronous RNA genotyping.Results: Of the 150 PLWH with LLV, 117 proviral DNA pol sequences detected in 105 PLWH were successfully amplified and RAMs were present in 27.6% and the rate of RAMs conferring low-level or greater resistance to antiretrovirals examined was 17.1%. Fifty-six and 57 PLWH had results of past and synchronous RNA genotyping, respectively, for comparisons with those of proviral DNA genotyping; and the concordance rates were 76.8% and 75.4%, respectively. However, proviral DNA genotyping lost than gained partial information on antiretroviral resistance compared with past or synchronous RNA genotyping.Conclusion: We found that the concordance between proviral DNA and past and synchronous RNA genotyping was moderate. Proviral DNA genotyping lost than gained more information on antiretroviral resistance compared with past or synchronous RNA genotyping. To optimize ART in PLWH with LLV, antiretroviral resistance profile should be interpreted in combination with proviral DNA and RNA genotyping and a comprehensive review of previous treatment history.Keywords: genotypic resistance testing, resistance-associated mutation, nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse-transcriptase inhibitor, protease inhibitor

Ruhai Bai,1 Jianmin Gao,2 Wanyue Dong3 1School of Public Affairs, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 2School of Public Policy and Administration, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Wanyue Dong, School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Qixia District, Nanjing, 210023, People’s Republic of China, Tel +86 25 858 11301, Email wanyuedong@njucm.edu.cnPurpose: Northwest China has a large area, low population density, and few health resources, which makes the utilization of health resources in this region difficult. The objective of this study was to assess utilization of health services and its association with travel time in Shaanxi Province.Patients and Methods: Data were obtained from the fifth Household Health Service Survey of Shaanxi Province conducted in 2013. Binary logistic regression was used to assess the relationship between travel time and health service utilization, and negative binomial regression was conducted to assess the relationship between travel time and the frequency of health service utilization.Results: A total of 42.6% of patients used health services, with a higher use rate among rural residents than among urban residents (47.0% and 27.4%, respectively). A total of 30.9% of patients traveled more than 15 min to the nearest medical facility (33.3% in rural areas and 22.6% in urban areas). A total of 12.4% of patients traveled more than 30 min to the nearest medical facility (15.1% in rural areas and 3.0% in urban areas). Urban residents living farthest from health care facilities (more than 30 min) had a 2.12-fold higher probability of health service utilization and expected to have a health service utilization rate 1.77 times greater than that of residents with a travel time of less than 5 min. Among the rural population, there was no significant correlation between travel time and health service utilization.Conclusion: Urban patients living farthest from hospitals were more likely to use health services and used health services more frequently. This suggests that more attention should be given to urban patients who live far away from health service providers in Shaanxi Province.Keywords: health equity, accessibility, travel time, health service utilization

Ruhai Bai,1 Wanyue Dong,2 Jinli Liu,3 Qiao Peng,3 Jun Lyu4 1School of Public Affairs, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 2School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of ChinaCorrespondence: Jun LyuDepartment of Clinical Research, The First Affiliated Hospital of Jinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong, People’s Republic of ChinaEmail lyujun2020@jnu.edu.cnPurpose: The Belt and Road Initiative (BRI) provided a platform to promote trade and economic collaboration, with health promotion also being an important component. This study examined the burden of the under-5 mortality rate (U5MR) among BRI countries and studied the impact of socioeconomic development on the U5MR.Patients and Methods: Data were collected from 137 BRI countries for the period 2000– 2018. The temporal changes in the U5MR and the estimated annual percentage change (EAPC) were used to assess the U5MR burden. A quantile fixed-effects model was used to access the associations between socioeconomic factors and the U5MR.Results: The U5MR varied widely among the 137 analyzed countries in 2018, being highest in Somalia (121.5 per 1000) and lowest in Slovenia (2.1 per 1000). The decreasing trend in U5MR was largest in Montenegro (EAPC = – 9.6, 95% confidence interval [CI] = – 10.2 to – 9.0), while the increasing trend was largest in Dominica (EAPC = 6.0, 95% CI = 5.3 to 6.7). Countries with higher U5MRs in 2000 experienced more rapid decreases in the U5MR from 2000 to 2018. The influence of socioeconomic factors on U5MR was related to the distribution of U5MR.Conclusion: The U5MR remains a major public-health issue in some BRI countries. Improving the economic situation will benefit child health in BRI countries in the long run.Keywords: Belt and Road, under-five mortality rate, socioeconomic, economic factors

Hui Huang,1 Minmin Li,2 Hourui Fan,3 Ruhai Bai4 1Department of Dermatology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Nutrition and Food Hygiene, Shaanxi Provincial Center for Disease Control and Prevention, Xi’an, Shaanxi, People’s Republic of China; 3Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4School of Public Affairs, Nanjing University of Science and Technology, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Ruhai BaiSchool of Public Affairs, Nanjing University of Science and Technology, No. 200, Xiaolingwei Street, Nanjing, Jiangsu, People’s Republic of ChinaEmail ruhaibai@hotmail.comPurpose: Urolithiasis is one of the commonest disease of the urinary system. This study aimed to assess the long-term urolithiasis incidence trends in China between 1990 and 2019.Patients and Methods: The incidence data of urolithiasis were extracted from Global Burden of Disease Study 2019, and an age–period–cohort framework was used to estimate the age, period, and cohort effects.Results: We found that the net drift was − 2.72% (95% CI: − 2.84% to − 2.60%) per year for men and − 2.14% (95% CI: − 2.24% to − 2.05%) per year for women, and except men in age group 0– 4, the local drift values were below 0 in all age groups (P< 0.05 for all) in both sexes during the period of 1990 to 2019. In the same birth cohort, the risk of incidence from urolithiasis rose first and then decreased with age for both sexes after controlling for period deviations, and in addition, after 20 years old, the risk of incidence of urolithiasis in men was higher than that in women (significantly with P< 0.05). In general, the estimated period and cohort relative risks were found in similar downward patterns for both sexes.Conclusion: In the past 30 years, the age-standard incidence of urolithiasis in both sex of Chinese people has decreased, but the crude incidence of urolithiasis in Chinese women has increased. Considering the aging of population structure in China, the overall number of female urolithiasis patients may increase, contributes to higher crude incidence rate. The problem of urolithiasis in Chinese women needs to be paid more attention.Keywords: age–period–cohort analysis, urolithiasis, urinary stones, urolithiasis in China

Sheng Yuan,1,2 Ying Shi,3 Minmin Li,4 Xiaojun Hu,5 Ruhai Bai6 1Department of New Medicine and Needle Pricking, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; 3School of Public Health, Shaanxi University of Chinese Medicine, Xi’an, Shaanxi, People’s Republic of China; 4Department of Infection Disease Control and Prevention, Shaanxi Provincial Center for Disease Control and Prevention, Xi’an, Shaanxi, People’s Republic of China; 5Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 6School of Public Affair, Nanjing University of Science and Technology, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Ruhai BaiSchool of Public Affair, Nanjing University of Science and Technology, No. 200, Xiao Lingwei Street, Nanjing, Jiangsu, People’s Republic of ChinaEmail ruhaibai@hotmail.comPurpose: Urinary tract infection (UTI) is the second-most-common type of infection in China. This study aimed to determine the long-term trends in the incidence of UTI in Mainland China between 1990 and 2019.Materials and Methods: Data were extracted from the Global Burden of Disease Study 2019 and were analyzed with the age–period–cohort framework.Results: The net drift in the incidence of UTI was – 0.37% (95% CI: – 0.40%, – 0.35%) in males and – 0.25% (95% CI: – 0.29%, – 0.20%) in females. For males, the local drift was lower than 0 (P< 0.05) among those younger than 90 years. For females, the local drift was lower than 0 (P< 0.05) among those younger than 60 years and higher than 0 (P< 0.05) in those aged 65– 79 years. In the same birth cohort, the incidence of UTI was higher in females than in males in all age groups (P< 0.05). The period relative risk (RR) showed a decreasing pattern after 2005 in both sexes. The cohort RR showed a downward trend of the birth cohort after 1905 for males and 1960 for females.Conclusion: The incidence has increased significantly among older females over the past 30 years. It is necessary to develop a comprehensive intervention plan for reproductive health services covering females and males of all ages.Keywords: age–period–cohort analysis, urinary tract infection, bacterial infection

Dan Liu,1 Jing-Jie Bai,2 Jun-Jie Yao,1 Yong-Bo Wang,1 Tong Chen,1 Qian Xing,1 Ran Bai1 1Department of Endocrinology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Endocrinology, Dalian Children’s Hospital, Dalian, Liaoning, People’s Republic of ChinaCorrespondence: Dan Liu; Ran BaiDepartment of Endocrinology, First Affiliated Hospital of Dalian Medical University, Zhongshan Str.222, Dalian, 116011, People’s Republic of ChinaEmail liudandan303114@163.com; bairan5556@163.comPurpose: To assess the association of type 2 diabetes mellitus (T2DM) and insulin glargine treatment with bone mineral density (BMD) in Chinese people.Methods: This retrospective study included 50 subjects with T2DM: 25 received oral glucose-lowering medication (ORL group), and 25 received oral glucose-lowering medication in combination with insulin glargine injection (CGI group). Thirty non-diabetic control subjects were also included. BMD was measured at lumbar vertebrae 1– 4 (L1–L4), spine bone mineral density (sBMD) results summary (L2–L4), femoral neck and trochanter by dual-energy x-ray absorptiometry.Results: Compared with non-diabetic controls, people with T2DM had significantly lower mean BMD at L2 (1.073± 0.120 vs 0.984± 0.158), L3 (1.094± 0.129 vs 0.991± 0.163) and L4 (1.089± 0.130 vs 0.982± 0.165) (all P< 0.05), significantly lower levels of serum calcium (2.02± 0.22 vs 2.27± 0.17 mmol/L, P< 0.05), PTH (24.19± 9.71 vs 31.52± 8.96 pg/mL, P< 0.05), and higher serum phosphate levels (1.43± 0.37 vs 1.20± 0.15 mmol/L, P< 0.05). The CGI group had higher L2, L3 and L4 BMD and sBMD (L2–L4) (P< 0.05), higher serum calcium levels (2.19± 0.11 vs 1.98± 0.20 mmol/L, P< 0.05) and lower serum phosphate levels (1.28± 0.20 vs 1.58± 0.43 mmol/L, P< 0.05) versus the ORL group. BMD and serum calcium levels were associated with the application of insulin glargine.Conclusion: These results suggest that insulin glargine may affect bone metabolism in patients diagnosed with T2DM. The study has implications for the selection of hypoglycemic agents for diabetic patients at risk of osteoporosis.Keywords: type 2 diabetes mellitus, insulin glargine, osteoporosis, bone mineral density

Wen Ma,1,2,* Wentao Wu,2,* Rong Fu,2 Shuai Zheng,3 Ruhai Bai,2 Jun Lyu1– 3 1Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China; 3Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun LyuClinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of ChinaTel +86 13379060167Email lyujun2020@jnu.edu.cnBackground: Suicide rate is much higher in cancer patients than in general population. This study examined the suicide risk in survivors of primary solid tumor across 19 cancer sites considering risk coincident patterns based on area-based SES indicators.Methods: A retrospective search of the SEER database was conducted. Independent risk factors for suicide were identified using the Cox proportional-hazards model. Exploratory factor analysis and cluster analysis were used to create coincident patterns of SES factors.Results: Suicide risk was higher for patients with a primary solid tumor who were older, male, white, unmarried, had no insurance, poorly differentiated, distant metastasis and did not undergo active treatment (especially surgery). The suicide risk was higher for patients living in areas with economic and education disadvantage, high levels of immigration and crowding, and high levels of residential instability. Concomitant presence of high economic and education disadvantage, high immigration and crowding levels and low residential instability, showed the highest risk of suicide.Conclusion: In order to mitigate suicidal risk, clinicians should pay more attention to patients who are older, male, white, not married, high levels of cancer severity, not received active treatment (especially surgery), and having no insurance. Identifying coincident patterns of suicide help further screen high suicidal risk patients based on area-based socioeconomic status.Keywords: socioeconomic status, suicide risk, solid tumor, exploratory factor analysis, cluster analysis, coincident patterns

Ruhai Bai,1,2 Wentao Wu,3 Wanyue Dong,3,4 Jinli Liu,3 Lili Yang,5 Jun Lyu1 1Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Evidence-Based Research Center of Social Science & Health, Public Affair School of Nanjing University of Science & Technology, Nanjing, People’s Republic of China; 3School of Public Health, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4School of Health Economics and Management, Nanjing Chinese Medicine University, Nanjing, People’s Republic of China; 5Department of General Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Jun LyuJinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong, People’s Republic of ChinaEmail lyujun2020@jnu.edu.cnPurpose: The objective of this study was to forecast the prevalence rates and the populations of overweight and obese in Chinese adults for 2030.Materials and Methods: Nine waves of China Health and Nutrition Survey (CHNS) data from 1991 to 2015 were used. A polynomial regression model was fitted to obtain the average BMI change trajectory of the population born in different years according to different sexes and residence areas (urban and rural). The model fitted to CHNS 2015 survey data was used to forecast the distribution of BMI and the prevalence rates of overweight and obesity in 15 years. The United Nations population forecast was then used to predict the proportions of overweight obese adults in all age groups in China in 2030.Results: The prevalence rates of overweight and obesity were projected to increase in both sexes and all geographic areas in future. By 2030, urban males will have the highest prevalence of overweight, 50.7% (95% CI: 47.5%, 53.9%). Except urban males, the prevalence of overweight and obesity in rural areas will exceed that in urban for both sexes. In 2030, the numbers of overweight and obese people in China aged 20– 89 years will reach 540 million and 150 million, respectively, which are 2.8 and 7.5 times higher compared to prevalences in 2000. In 2030, the number of overweight and obese people in China aged 60– 89 years will reach 200 million and 40 million, respectively, 6.3 and 8.5 times increments from the year 2000.Conclusion: The prevalence rates of overweight and obese in Chinese adults are projected to increase further, by 2030 more than half of adult males living in urban areas will be overweight. Combined with changes in the population age structure, overweight and obesity will have a huge impact on the health of the Chinese population over the next 15 years.Keywords: aging, BMI, prediction, population; overweight; obesity

Yan Wang,1 Meng Zhao,2 Huishan Zhao,3 Shi Cheng,1 Rixing Bai,1 Maomin Song11Department of General Surgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Breast Surgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of ChinaBackground: Metastasis-associated with colon cancer-1 (MACC1) is an important regulator that promotes colorectal cancer (CRC) cells’ proliferation and distant metastasis. Therefore, MACC1 is considered as a promising therapeutic target of CRC. This work aimed to identify the microRNA (miR) targeted to MACC1, and to study the potential of using the particular miR in enhancing the antitumor effect of chemotherapy.Materials and methods: miR prediction was performed in the miR database. The effect of miR-940 on MACC1’s expression was examined by Western blot, and the effect of miR-940 on the expression of genes related to the epithelial–mesenchymal transition (EMT) was identified by quantitative real-time polymerase chain reaction experiments. In vivo growth of CRC cells were analyzed in the nude mice subcutaneous tumor model and CRC liver metastasis model.Results: By using the database, miR-940 was identified to target to the 3ʹUTR of MACC1’s mRNA. Experimentally, transfection of miR-940 decreased the expression of MACC1 in CRC cells and inhibited the EMT process of the transfected cells. MiR-940 also enhanced the inhibitory effect of Anlotinib on CRC cells’ in vivo growth and invasion. Correspondingly, ectopic expression of MACC1 mutant, which does not contain miR-940 binding site, blocked the antitumor effect of miR-940 on CRC cells.Conclusion: MiR-940 restricts the proliferation and invasion of CRC cells by targeting to MACC1’s mRNA, and enhances the antitumor effect of Anlotinib on CRC tumors.Keywords: colorectal cancer, Anlotinib, metastasis-associated gene in colon cancer 1, proliferation, in vivo invasive growth

Weiting Ge,1 Wen Cai,1,2 Rui Bai,1 Wangxiong Hu,1 Dehao Wu,1,2 Shu Zheng,1 Hanguang Hu1,2 1Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; 2Department of Medical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China Background: Hypermutated colorectal cancer (CRC) reportedly accounts for 15%–17% of all cases of CRC. However, the proportion and number of patients with hypermutated CRC cannot be unappreciated. Additionally, therapy options for these patients differ from those for CRC patients, with a greater potential benefit from immunotherapy. Materials and methods: We sequenced the tumor mucosa of CRC patients with >24 months of follow-up data at our center and identified mutation profiles of hypermutated CRC as a training data set (Zhejiang University [ZJU]); we then collected patients from The Cancer Genome Atlas (TCGA) as a validation data set. Recurrently mutated genes were combined to calculate a compound score via Cox proportional hazards model. Patients with higher-than-median scores were segregated as the high-risk group. Outcomes were analyzed by Kaplan–Meier and Cox regression analyses using Python (3.6.0) and R (3.4.0). Results: We constructed a 4-gene signature (ACVR2A, APC, DOCK2, and POLE), with training in 45 hypermutated patients at ZJU and validation in 24 hypermutated patients from TCGA. Patients in the high-risk group showed poor survival (adjusted HR =9.85, 95% CI: 2.07–46.81, P=0.004). Further subgroup analysis was performed for stage II and III colon cancer (HR =10.91, 95% CI: 1.36–87.5, P=0.005) and high microsatellite instability (MSI-H) CRC (HR =12.57, 95% CI: 1.57–100.69, P=0.002) subgroups, which verified that our signature is universal. We then compared our prognostic signature with other risk factors (including MSI status, POLE driver mutation, BRAF-p.V600E, tumor mutational burden, and TNM staging). The results proved that our 4-gene signature is better than the other risk factor for prognosis in hypermutated CRC.Conclusion: Our 4-gene signature is a good predictor of survival for hypermutated CRC, and this signature is powerful in stage II and III colon cancer and MSI-H CRC. Future prospective studies are needed to confirm the power of the 4-gene signature in patients receiving immunotherapy. Keywords: colorectal cancer, hypermutation, gene signature, prognosis

Zhaoxia Zhang,* Dong Zhao,* Mei Lin, Dongxue Zhang, Ruijuan Bai, Jing Fan, Zuomin Wang Department of Stomatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Objectives: Based on the concept of health quotient (HQ), we designed and facilitated personalized plans to improve patients’ compliance and oral health. The study aims to increase HQ level of patients with chronic periodontitis from four aspects, namely self-care, health knowledge, lifestyle, and mental health, and evaluate the effects of HQ training in maintaining oral health.Method: In total, 105 patients with chronic periodontitis were recruited from Capital Medical University-Affiliated Beijing Chaoyang Hospital from January 2015 to January 2017. The patients were randomly split into two groups (control versus test). All the patients received standard periodontal treatments. In addition, patients in the control group received conventional oral health instructions, and patients in the test group received the HQ training. At the end of the training, oral health status of both groups was evaluated and recorded.Results: The oral health status and the HQ scores were significantly better in the test group than the control group (P

Xifu Wang,1 Kangan Li,1 Haoran Sun,2 Jinglong Zhao,1 Zhuoli Zhang,3 Linfeng Zheng,1 Weiguo Li,3 Renju Bai,2 Guixiang Zhang11Department of Radiology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 2Department of Radiology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAAbstract: To explore the correlation between the typical findings of dynamic contrast-enhanced computed tomography (DCE-CT) and tumoral angiogenesis (microvessel density [MVD] and vascular endothelial growth factor [VEGF]) in adenomas and nonadenomas such that the enhancement mechanism of DCE-CT in adrenal masses can be explained more precisely. Forty-two patients with 46 adrenal masses confirmed by surgery and pathology were included in the study; these masses included 23 adenomas, 18 nonadenomas, and 5 hyperplastic nodules. The findings of DCE-CT and angiogenesis in adrenal masses were studied. The features of DCE-CT in adenomas and nonadenomas were evaluated to determine whether the characteristics of DCE-CT in adrenal masses were closely correlated with tumoral angiogenesis. Adrenal adenomas were significantly different from nonadenomas in the time density curve and the mean percentage of enhancement washout at the 7-minute delay time in DCE-CT. The mean MVD and VEGF expression exhibited significant differences between the rapid washout group (types A and C) and the slow washout group (types B, D, and E) and between the relative washout (Washr) ≥34% and the absolute washout (Washa) ≥43% on the 7-minute enhanced CT scans (P=0.000). Adenomas were suggested when adrenal masses presented as types A and C, and/or the Washr ≥34%, and/or the Washa ≥43%, and the opposite was suggested for nonadenomas. These results showed a close correlation between the characteristics of DCE-CT and both MVD and VEGF expression in adrenal masses. There was also a significant difference in MVD and VEGF expression between adenomas and nonadenomas. In conclusion, MVD and VEGF expression are two important pathological factors that play important roles in the characterization of DCE-CT in adrenal masses because they cause different time density curve types, the Washr and the Washa for adrenal adenomas and nonadenomas.Keywords: tumoral angiongenesis, adrenal adenomas and nonadenomas, x-ray computed tomography, biomarker, diagnosis

Inflammatory bowel disease (IBD) is a debilitating condition that can lead to life-threatening complications. Macrophages are crucial in IBD management because they secrete various cytokines and regulate tissue repair. Macrophage-derived angiogenin (ANG) has been shown to be essential for limiting colonic inflammation, but its upstream regulatory pathway and role in macrophages remain unclear. Here we show that ANG expression is up-regulated in macrophages during colitis treatment or upon lipopolysaccharides (LPS) treatment. Mechanistically, LPS activates Toll-like receptor 4 (TLR4) to initiate NF-κB translocation from the cytoplasm to the nucleus, where it binds to the ANG promoter and enhances its transcriptional activity, leading to increased ANG expression. Interestingly, our data also reveal that the deletion of ANG in macrophages has no adverse effect on key macrophage functions, such as phagocytosis, chemotaxis, and cell survival. Our findings establish a “LPS-TLR4-NF-κB-ANG” regulatory axis in inflammatory disorders and confirm that ANG controls inflammation in a paracrine manner, highlighting the importance of ANG as a key mediator in the complex network of inflammatory processes.