ObjectiveTo investigate the effects and potential mechanisms of morning and evening fasting on postprandial lipid responses, a post hoc analysis based on a crossover randomized controlled trial was conducted to assess the effects of different fasting strategies on postprandial lipid metabolism in community residents in Shanghai. MethodsA total of 23 participants took part in a randomized crossover trial involving two intervention days: morning fasting and evening fasting, with a washout period of 6 days between intervention days. Two-way analysis of variance was used to test the differences in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the relative expression of circadian clock genes before and after the next meal under fasting. Wilcoxon rank sum tests were used to analyze the different metabolites between the two groups. Principal component analysis and Orthogonal partial least squares-discriminant analysis were conducted to evaluate the ability of metabolites to differentiate between morning fasting and evening fasting and identify the important differential metabolites. After adjusting for age, sex, and BMI, a partial correlation analysis was performed to identify metabolites associated with plasma lipids. In addition, important metabolites associated with plasma lipids were computed by pathway enrichment analysis. ResultsAfter evening fasting intervention, fasting TG level [(0.37±0.29) vs (0.27±0.18)] mmol·L^-1, fasting and postprandial change values in TC [(2.74±0.47) vs (2.51±0.27)] mmol·L^-1 and LDL-C [(1.32±0.38) vs (0.99±0.27)] mmol·L^-1 were significantly lower than those after morning fasting (P<0.05). While, change values of fasting LDL-C [(0.89±0.37) vs (1.14±0.37)] mmol·L^-1 and TG [(1.14±0.19) vs (1.28±0.17)] mmol·L^-1 were significantly higher than those after morning fasting intervention (P<0.05). After fasting intervention, the relative expression of AMPK, CRY1, CLOCK, MTNR1B, AANAT, and ASMT was correlated with the amount of plasma lipid changes (P<0.05). Specifically, CLOCK and AANAT were upregulated following evening fasting and downregulated after morning fasting. Among the 217 important differential metabolites, 111 were correlated with plasma lipids, and which were primarily enriched in the cysteine and methionine metabolism pathways (P<0.05). ConclusionCompared to morning fasting, evening fasting was more effective in improving postprandial lipid responses, indicating that an evening fasting window during intermittent fasting could be conducive to cardiovascular disease prevention in adults. Meanwhile, it is suggested that morning and evening fasting may affect lipid responses through circadian rhythm oscillations and the cysteine and methionine metabolism pathways.

Lung cancer （LC） is a significant global public health issue， with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually， posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However， postoperative multidimensional functional impairments， including respiratory， mucosal， and psychological functions， are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration， but also negatively correlate with prognosis， facilitating disease recurrence and metastasis. At present， postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine （TCM） differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery， and guided by the classical TCM theory of "lungs governing Qi"， this study， based on the core concept of the "five perspectives on treatment" theory， innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase， mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase， and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly， stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase， the strategy emphasizes tonifying Qi and uplifting sinking Qi， with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase， the approach focuses on nourishing Yin and uplifting Qi， with prescription combinations that integrate unblocking and tonification. In the consolidation phase， the strategy aims to resolve constraint and uplift Qi， with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation， clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM， offering a new approach for TCM differentiation and treatment in the full-cycle， stage-based， and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.

Tumor treatment-related adverse reactions are a major focus of clinical concern， among which recurrent aphthous oral ulcers （RAU） associated with targeted therapy for lung cancer （LC） are among the most painful and distressing for patients. Currently， modern medical interventions show limited efficacy， and there is an urgent need for more effective treatment strategies. This study differentiates RAU associated with targeted therapy for LC from chemotherapy-related and ordinary oral ulcers， elucidates the pathophysiological basis of such ulcers， and traces the theoretical origin of "Yin deficiency and Qi collapse". Based on the new system of "five perspectives on diagnosis and treatment" for tumor prevention and treatment， with a focus on the core and symptom perspectives and rooted in the traditional concept of "lung dominating Qi"， we innovatively propose the concept of "medicine-induced ulcer" and are the first to introduce the theory of "Yin deficiency and Qi collapse" into the syndrome differentiation and treatment of RAU associated with targeted therapy for LC （i.e.， medicine-induced ulcer）. We propose that "Yin deficiency and Qi collapse" is the core pathogenesis of medicine-induced ulcers， in which the collapse of formless Qi is the key to their onset， while the deficiency and stasis of tangible Yin and blood constitute the root of recurrence. A hierarchical strategy for syndrome differentiation and treatment is established： first treating the collapse of formless Qi， then replenishing tangible deficiencies， and concurrently preventing recurrence. We emphasize that treatment should address both root and manifestation， with appropriate prioritization. In the acute phase， while relieving symptoms and promoting ulcer healing by nourishing Qi， uplifting collapse， and generating body fluids， attention should also be paid to nourishing spleen Yin， facilitating the circulation of nutritive Qi， and alleviating stasis to target the root pathogenesis and reduce recurrence. A verified case is presented to support this approach. This study enriches the theoretical framework and clinical methods of traditional Chinese medicine （TCM） in the treatment of RAU associated with targeted therapy for LC， promotes symptom management of treatment-related adverse reactions through integrated TCM and Western medicine， and provides theoretical support for the construction and development of a comprehensive differentiation and treatment system for lung cancer prevention， treatment， and rehabilitation.

Objective: To explore the association between lifestyle and fat mass index (FMI) in different positions of children and adolescents aged 7-18, so as to provide a scientific basis for health promotion in children and adolescents. Methods: A total of 1 531 students aged 7-18 was selected by intentional sampling from 4 schools in Tongzhou District, Beijing from September to December in 2020 and August in 2022. Questionnaire survey was used to collect lifestyle including dietary behavior, moderate to vigorous physical activity, smoke and drink behaviors, sleep time and sleep quality. Dual energy Xray absorptiometry was employed to assess fat mass, and calculated total, android, trunk, hip, gynoid and leg fat mass index (FMI). The ttest and Chisquare test were used to compare the differences of different lifestyle. Logistic regression was used to analysis association between lifestyle and body composition in different positions. Results: Compared with healthy lifestyle, unhealthy lifestyle had higher risk for hightrunk FMI (OR=1.40, P<0.05). After adjusted for sex and age, unhealthy lifestyle had higher risk for hightotal FMI, highandroid FMI, hightrunk FMI (OR=1.37, 1.37, 1.50, P<0.05), compared with healthy lifestyle. Stratified analysis found the associations between unhealthy lifestyle and hightotal FMI, highandroid FMI, hightrunk FMI, and highthigh FMI were only significant in girls with 7-12 years old (OR=2.13, 2.46, 2.13, 2.13, P<0.05). Conclusions Unhealthy lifestyle is associated with hightotal FMI, highandroid FMI and hightrunk FMI. A healthy lifestyle should be maintained during puberty, especially before puberty, to help children and adolescents reduce body fat and promote a balanced distribution of body composition.

Objective To assess the impact of ultrasound-guided fascia iliaca compartment block on major cardiovascular events and postoperative prognosis in patients with lower limb aortoiliac occlusive disease(ASO).Methods This study was a retrospective study including 353 patients with lower limb arterial reconstruction surgery for ASO at Xiamen Hospital Affiliated to Zhongshan Hospital of Fudan University from January 2018 to January 2022.Patients were divided into two groups based on different anesthesia:the group receiving ultrasound-guided fascia iliaca block combined with sciatic nerve block(Group B)and the group receiving monitored anesthesia care(MAC)(Group M).The primary outcome was the occurrence of major adverse cardiovascular events after lower limb arterial reconstruction surgery in ASO patients.The secondary outcomes included the incidence of non-cardiac postoperative myocardial injury,postoperative amputation,and other adverse reactions such as postoperative delirium,nausea,and vomiting as well as postoperative laboratory indicators.By using propensity score matching to balance baseline characteristics before surgery,the impact of different anesthesia methods on the occurrence of MACE and prognosis after surgery in ASO patients was analyzed.Results After propensity score matching,the incidence of MACE in Group B was lower compared with Group M(10%vs.3.4%,P=0.038);The incidence of MINS in Group B(33%vs.25%,P=0.200);The amputation rate of Group B(4.2%vs.3.4%,P＞0.99);The incidence of complications in Group B was(6.8%vs.4.2%,P=0.39);There was no statistically significant differ-ence in postoperative laboratory indicators between the two groups(P＞0.05).Multivariate analysis showed that nerve block(OR=0.25,95%CI:0.05～0.93),postoperative HBG(OR=0.95,95%CI:0.91～0.99)were in-dependent factors in reducing the incidence of MACE.Conclusion Ultrasound-guidance fascia iliaca compartment block and sciatic nerve block could reduce the risk of major adverse cardiovascular events in patients undergoing lower limb arterial revascularization surgery.

OBJECTIVE To set up normal ranges for indexes in embryo-fetal development toxicity studies in Sprague-Dawley(SD)rats and to establish a background database to provide reference for the embryo-fetal development toxicity evaluation of drugs.METHODS The data on embryonic develop-ment and fetal growth from embryo-fetal development toxicity studies(11 items)conducted by our center between 2013 and 2022 was statistically analyzed,involving 205 pregnant rats and 3037 fetuses in total,with the mean and standard deviation,coefficient of variation and 95%confidence interval calculated.The indexes included body mass,body mass gain and food consumption during pregnancy,pregnancy outcomes(pregnancy rate,average corpora lutea,average Implant sites,average live conceptuses,live conceptuse rate,resorption rate and dead conceptuse rate),fetal growth and development(fetal mass,placental mass and sex ratio),appearance abnormality rate,visceral abnormality rate,and skeletal abnormality rate.RESULTS The mass of pregnant rats trended up during gestation,with significant increases in the late period.Food consumption increased along with gestation.Caesarean section was conducted on gestation day 20,and the pregnancy rate was 93.2%.The average corpora lutea,Implant sites and live conceptuses were 18.0±3.2,15.9±2.8 and 14.8±3.0,respectively.The live conceptuse rate was 93.4%while the total dead embryo rate was 6.6%.The average mass of fetuses and placenta were respectively 3.6±0.3 and(0.6±0.3)g,and the fetal sex ratio(male/female)was 0.94.The incidence of fetal appearance abnormalities was about 0.2%,and that of soft tissue abnormalities was approximately 0.8%.The rate of skeletal abnormalities was about 1.2%,with higher incidence of non-ossification and incomplete ossification mostly identified on sternum and hyoid bone.The numbers of ossifications of metacarpal bones,metatarsal bones and sacrococcygeal vertebrae were 7.0±0.7,8.0±0.1 and 7.4±0.5,respectively.The rate of ossification of sternumⅠtoⅣwas higher,with an average of about 98.6%-99.9%.The ossification rates of sternum Ⅴ and Ⅵ were(68.0±28.4)%and(82.8±23.9)%.CONCLUSION The background database of indexes in the embryo-fetal development toxicity study on SD rats is established for our GLP laboratory,which provides reference for reproductive toxicity studies.

Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.
Nucleic Acids ; RNA, Small Interfering/genetics* ; Drug Carriers ; Drug Delivery Systems ; Drug Development

ObjectiveTo investigate the value of MELD 3.0， MELD， and MELD-Na scores in assessing the 90-day prognosis of patients with acute-on-chronic liver failure （ACLF） through a comparative study. MethodsA retrospective analysis was performed for the clinical data of 605 patients with ACLF who were treated in Tianjin Third Central Hospital， The Fifth Medical Center of Chinese PLA General Hospital， and Beijing YouAn Hospital from November 2012 to June 2019， and according to the 90-day follow-up results after admission， they were divided into survival group with 392 patients and death group with 213 patients. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， net reclassification improvement （NRI）， integrated discrimination improvement （IDI）， and decision curve analysis （DCA） curve were used to investigate the value of MELD 3.0， MELD， and MELD-Na scores at baseline， day 3， week 1， and week 2 in predicting the prognosis of the disease. ResultsAt day 3 and week 1， MELD 3.0 score had an AUC of 0.775 and 0.808， respectively， with a better AUC than MELD score （P<0.05）. At day 3， week 1， and week 2， MELD 3.0 score showed an NRI of 0.125， 0.100， and 0.081， respectively， compared with MELD in predicting the prognosis of ACLF patients， as well as an NRI of 0.093， 0.140， and 0.204， respectively， compared with MELD-Na score in predicting prognosis. At baseline， day 3， week 1， and week 2， MELD 3.0 showed an IDI of 0.011， 0.025， 0.017， and 0.013， respectively， compared with MELD in predicting the prognosis of ACLF patients. At day 3 and week 2， MELD 3.0 showed an IDI of 0.027 and 0.038， respectively， compared with MELD-Na in predicting the prognosis of ACLF patients. All the above NRIs and IDIs were >0， indicating a positive improvement （all P<0.05）. DCA curves showed that MELD 3.0 was superior to MELD at day 3 and was significantly superior to MELD-Na at week 2. There was no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with different types， and there was also no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with the etiology of HBV infection， alcohol， or HBV infection combined with alcohol， while MELD 3.0 was superior to MELD for ACLF patients with other etiologies （P<0.05）. ConclusionMELD 3.0 score is better than MELD and MELD-Na scores in predicting the 90-day survival of patients with ACLF， but with limited superiority.

Objective:To observe the influence of shared medical appointments on health-related quality of life and quality of sleep in patients after liver transplantation.Methods:By randomized controlled study, a total of 124 patients after liver transplantation were included from our hospital from January 2018 to January 2019, and according to the lottery method, all subjects were divided into the routine management group ( n=64) who received routine outpatient intervention and the shared medical management group ( n=60) who received shared medical appointments management. The health-related quality of life and quality of sleep were investigated and compared by post-liver transplant quality of life questionnaire (pLTQ) and Pittsburgh sleep quality index (PSQI) before intervention (the day of discharge) and after intervention (the end of the last shared outpatient service). Results:After intervention, the dimension scores of worry, economics, body function, emotional function, health service, complication and total score of pLTQ were improved in tow groups than before intervention [the routine management group: (41.90±7.61), (18.13±4.22), (22.22±5.10), (14.92±3.28), (20.39±4.87), (14.63±3.99), and (132.19±37.09) vs (32.25±5.55), (12.77±3.47), (17.58±4.72), (9.23±1.38), (15.17±4.81), (10.89±1.51) and (98.00±29.03) score, t=8.20, 7.85, 3.58, 12.79, 6.10, 7.01, 5.81, all P<0.001; shared medical management group: (46.12±7.92), (24.16±5.34), (25.55±5.42), (17.90±3.60), (24.81±5.12), (17.93±3.60) and (155.47±41.00) vs (32.57±5.69), (12.81±3.82), (17.00±4.70), (9.60±1.39), (15.39±4.84), (11.00±3.52) and (98.37±28.96) score, t=10.76, 13.39, 9.23, 16.66, 10.36, 10.66, 8.81, all P<0.001], and those in the shared medical management group were higher than those in routine management group ( t=3.03, 6.95, 3.53, 4.82, 4.93, 4.83, 3.32, all P<0.05). After intervention, the total score of PSQI scale were lower than before intervention in the routine management group [(10.48±2.14) vs (11.89±2.45) score, t=3.47, P=0.001], and the dimensions score of sleep quality, full-sleep time, sleep time, sleep efficiency, sleep disorders, daytime function, hypnotic and total score of PSQI were lower than before intervention in the shared medical management group [(1.41±0.32), (0.54±0.13), (1.17±0.26), (1.11±0.35), (1.21±0.27), (1.30±0.33), (1.08±0.21) and (8.05±1.75) vs (1.88±0.53), (0.86±0.37), (1.84±0.41), (2.05±0.56), (1.39±0.33), (1.47±0.43), (1.22±0.32) and (11.71±2.43) score, t=-5.88, -6.32, -10.69, -11.03, -3.27, -2.43, -3.65, -9.47, all P<0.05], and those in the shared medical management group were lower than those in routine management group ( t=-6.68, -6.39, -10.43, -10.97, -2.62, -2.12, -3.54, -6.90, all P<0.05). Conclusion:Shared medical appointments model can improve the health-related quality of life and quality of sleep in patients after liver transplantation, and improve the effectiveness of outpatient intervention.

OBJECTIVES: To provide reference basis for reducing the mortality for children under 5 years old and promote the healthy development, the mortality for children under 5 years old and the main causes for death in Liuyang City from 2013 to 2020 are analyzed. METHODS: The data of 725 cases of death for children under 5 years old in Liuyang City from 2013 to 2020 were collected.The causes and difference of death among the children were analyzed retrospectively by descriptive statistic methods. RESULTS: There were a total of 144 516 live births in Liuyang City from 2013 to 2020. The mortality for children under 5 years old was 5.01‰, for infants was 3.39‰, and for newborns was 1.63‰. The male child mortality was 5.28‰, and the female child mortality rate was 4.72‰, with significant difference (P>0.05). The mortality for children under 5 years old was seasonal fluctuation, without significant difference among seasons (P>0.05). For the past 5 years, the top 3 causes for death among children under 5 years old were preterm birth and low birth weight, congenital heart disease, and pneumonia. Before death, 341 cases (47.04%) were treated in provincial hospitals, 198 cases (27.31%) in county-level hospitals, 56 cases (7.72%) in village-level hospitals, and 130 cases (17.93%) were not treated. CONCLUSIONS The mortality for children under 5 years old in Liuyang City is gradually reduced in the past 5 years. The main causes for death are premature birth and low birth weight, congenital heart disease and pneumonia. We should develop healthy education, improve the rate of prenatal diagnosis, promote the construction of obstetrics and paediatrics, and fundamentally reduce the mortality for children under 5 years old.
Cause of Death ; Child ; Child Mortality ; Child, Preschool ; Female ; Heart Defects, Congenital ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Male ; Pneumonia/epidemiology* ; Pregnancy ; Premature Birth ; Retrospective Studies