Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.
Male ; Humans ; Urethral Stricture/etiology* ; Retrospective Studies ; Constriction, Pathologic/surgery* ; Lichen Sclerosus et Atrophicus/surgery* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; China ; Urethra/surgery* ; Postoperative Complications/etiology* ; Mouth Mucosa ; Diabetes Mellitus/etiology* ; Anticoagulants ; Coronary Disease

OBJECTIVES: The prevalence rate of sleep problems in children in China is increasing in recent years. There are inconsistencies in the relationship between physical activity and sleep, and the impact of screen time on young children seems more obvious.This study aims to understand the current situation of outdoor activity time, screen time and sleep (total sleep duration, bedtime, and wake-up time) and the associations between outdoor activity time and screen time with sleep for children aged 36-54 months in Kaifu District of Changsha. METHODS: Using the cluster sampling method, 1 286 newborns delivered in 3 community health service centers in Kaifu District, Changsha from January to December 2015 were selected as the research subjects to establish a prospective birth cohort. According self-designed questionnaire and household follow-up to select 36, 42, 48, 54 months Children's data. The mixed linear model was used to explore the associations of outdoor activity time and screen time with sleep. RESULTS: The 36-54 months children's total sleep duration was decreased from 11.60 h/d to 10.92 h/d (P<0.001); bedtime time delayed from 21:58 to 22:00 (P=0.124); wake-up time advanced from 7:52 to 7:37 (P<0.001); outdoor activity time was decreased from 2.58 h/d to 1.94 h/d (P<0.001), and screen time was decreased from 1.28 h/d to 1.09 h/d (P<0.001). With aging, the prevalence of sleep <10 h/d and outdoor activity time <2 h/d was increased significantly, and the prevalence of screen time ≥1 h/d was decreased (P<0.05). Mixed linear models showed that longer outdoor activity time was related to increased total sleep duration (β=0.22, 95% CI 0.00 to 0.44) and delayed wake-up time (β=0.16, 95% CI 0.00 to 0.32), and longer screen time was related to delayed bedtime (β=0.22, 95% CI 0.05 to 0.39) and wake-up time (β=0.24, 95% CI 0.08 to 0.41). These associations were different in gender. Longer outdoor activity time was related to delayed wake-up time (β=0.37, 95% CI 0.14 to 0.59) in boys, but not in girls (β=-0.16, 95% CI -0.33 to 0.01). Longer screen time was associated with delayed bedtime (β=0.40, 95% CI 0.09 to 0.63) and wake-up time (β=0.33, 95% CI 0.15 to 0.51) in girls, but only related to delayed wake-up time (β=0.29, 95% CI 0.06 to 0.52) in boys, and the degree of association was lower than that of girls. CONCLUSIONS Among children aged 36-54 months in Kaifu District, Changsha, there are problems including going to bed late and getting up late, insufficient physical activity, and long screen time. Outdoor activity time and screen time are related to sleep. Increasing outdoor activity time and reducing screen time can help to improve children's sleep.
Infant, Newborn ; Male ; Child ; Female ; Humans ; Child, Preschool ; Screen Time ; Cohort Studies ; Birth Cohort ; Prospective Studies ; Sleep

Objective:To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China.Methods:From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model.Results:The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low.Conclusions:The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.

Objective:To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China.Methods:From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model.Results:The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low.Conclusions:The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.

Objective To investigate the risk of Anisakis infections among high-risk populations along the coastal areas of Jiangsu Province, so as to develop the strategy for the prevention and control of anisakiasis in the province. Methods Three counties along the coastal areas of Jiangsu Province were selected as the study sites in 2018, including Rudong County in Nantong City, Haizhou District in Lianyungang City and Dongtai City in Yancheng City. The knowledge, attitude and practice (KAP) of anisakiasis prevention and control, and the prevalence of serum specific IgG antibody against Anisakis were investigated among high-risk populations among these three study sites, including fishermen, fish seller and people who liked eating fresh and live marine fish. Factors affecting the prevalence of the specific IgG antibody against Anisakis were identified using a multiple logistic regression model. In addition, Anisakis larvae infections were detected in fresh and live marine fish samples collected from local markets, and the prevalence and intensity of Anisakis infections were estimated. Results A total of 625 high-risk populations were investigated, including 349 men (55.8%). Only 13.0% of the subjects heard about anisakiasis, and a low awareness rate of anisakiasis prevention and control knowledge was seen among these three types of high-risk populations. There were 21.6% of the subjects eating raw or half-cooked marine fish, 5.8% eating undercooked marine fish, 3.2% presenting vomiting, nausea and diarrhea after eating marine fish, 5.1% developing systemic allergic symptoms, and 65.6% using the same chopping board for raw and cooked food. The sero-prevalence of the anti-Anisakis IgG antibody was 7.0% among the study subjects. Multiple logistic regression analysis identified education level [OR = 0.687, 95% CI (0.478, 0.987)] and development of systemic allergic symptoms [OR = 4.641, 95% CI(1.411, 15.268)]as factors affecting the positive anti-Anisakis IgG antibody among the study subjects. Among 494 fresh and live marine fish detected, the prevalence and intensity of Anisakis larvae infection was 64.0% and 8.1 larvae per fish, with high prevalence seen in Trichiurus haumela and Pneumatophorus japonicas. Conclusions The awareness of anisakiasis prevention and control knowledge is low among the high-risk populations living along the coastal areas of Jiangsu Province, and there are high-risk behaviors, such as eating raw or half-cooked food, using the same chopping board for raw and cooked food. In addition, the prevalence of Anisakis infections is high in the marine fish in these areas. Therefore, the health education and health promotion for anisakiasis prevention and control should be intensified.