Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

A natural experiment is a causal inference study design grounded in real-world research. Its core concept is to use quasi-random variation in exposure generated by external factors to evaluate the effects of interventions or exposures on outcomes. It is particularly suitable for research settings in which randomized controlled trials （RCTs） are infeasible or ethically constrained， and it combines causal inference capacity with relatively strong external validity. This article provides an overview of the definition， key features， and current application status of natural experiments， and proposes the application scenarios for applying natural experiment strategies to the evaluation of therapeutic effects in traditional Chinese medicine （TCM）， including policy implementation or policy change evaluation， assessment of variations in clinical practice within hospitals， and evaluation of differences in resource allocation across regions or institutions. The design pathway includes starting from clinical or policy-related TCM questions， systematically collecting relevant data， performing statistical modeling and effect estimation， and interpreting effect estimates in the context of clinical practice. It further analyzes the advantages and challenges of using natural experiments in TCM.

A natural experiment is a causal inference study design grounded in real-world research. Its core concept is to use quasi-random variation in exposure generated by external factors to evaluate the effects of interventions or exposures on outcomes. It is particularly suitable for research settings in which randomized controlled trials （RCTs） are infeasible or ethically constrained， and it combines causal inference capacity with relatively strong external validity. This article provides an overview of the definition， key features， and current application status of natural experiments， and proposes the application scenarios for applying natural experiment strategies to the evaluation of therapeutic effects in traditional Chinese medicine （TCM）， including policy implementation or policy change evaluation， assessment of variations in clinical practice within hospitals， and evaluation of differences in resource allocation across regions or institutions. The design pathway includes starting from clinical or policy-related TCM questions， systematically collecting relevant data， performing statistical modeling and effect estimation， and interpreting effect estimates in the context of clinical practice. It further analyzes the advantages and challenges of using natural experiments in TCM.

[Objective]To explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment(MCI).[Methods]Based on the baseline survey of the Hubei memory and aging cohort study(2018-2023),the participants completed a thorough neuropsychological assessment and physical examination,and self-reported a history of general anesthesia and surgery.The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model.In addition,the stratification and interaction analysis of anesthesia history,anesthesia number and physical intellectual exercise were conducted separately.[Results]A total of 5 069 older adults aged 65 and above were included in this study,including 3 692 city dwellers and 1 377 rural people,among whom were 2 584 women(51%).Out of the 1 472 participants with history of general anesthesia,249 people(17.4%)had MCI.After controlling for confounding factors,there was a 39.6%increased risk of MCI in older adults who underwent general anesthesia[OR=1.396,95%CI(1.169,1.668),P<0.001],suggesting that general anesthesia may be an independent influence on MCI.For the older adults who had one general anesthesia[OR=1.235,95%CI(1.001,1.523),P=0.049],two general anesthesia[OR=1.779,95%CI(1.292,2.450),P<0.001],and three OR more general anesthesia[OR=2.395,95%CI(1.589,3.610),P<0.001],their risks of MCI were increased by 23.5%,77.9%,and 139.5%,respectively.Compared with the older adults without a history of general anesthesia who did not exercise,the risk of developing MCI was significantly negatively correlated with the exercise group,cognitive exercise group,and combined exercise and cognitive exercise groups(all P<0.001).The risk of developing MCI in the exercise group was 60.2%of that in the no exercise group[OR=0.602,95%CI(0.456,0.795)],the risk in the cognitive exercise group was 42.4%of that in the no exercise group[OR=0.424,95%CI(0.294,0.613)],and the risk in the combined exercise and cognitive exercise group was 27.0%of that in the no exercise group[OR=0.270,95%CI(0.208,0.353)].In the older adults with a history of general anesthesia,compared with the no exercise group,the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group(all P<0.05).The risk of developing MCI in the cognitive exercise group was 47.7%of that in the no exercise group[OR=0.477,95%CI(0.256,0.892)],the risk in the combined exercise and cognitive exercise group was 34.5%of that in the no exercise group[OR=0.345,95%CI(0.220,0.540)],while the risk in the exercise-only group did not show a significant difference.[Conclusion]The risk of MCI increased significantly in older adults with a history of general anesthesia,and this risk increased with the times of anesthesia.Physical and mental exercise reduces the risk of MCI.it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.

Objective:To explore the effect of persuasion system-based health intervention in orthodontic patients treated with clear aligners.Methods:From January 2022 to December 2023, convenience sampling was used to select patients treated with clear aligners at the Department of Orthodontics in Affiliated Stomatological Hospital of Nanjing Medical University as participants. Patients admitted from January to December 2022 were included in the control group ( n=60), and those admitted from January to December 2023 were included in the observation group ( n=59). The control group received health guidance based on the theory of knowledge, attitude, and practice. Based on the control group, the observation group added health intervention with the assistance of a persuasion system. After one year of intervention, the oral care self-efficacy, enamel demineralization, periodontal health index (gingival index, plaque index, sulcus bleeding index, probing depth), and restart rate of both groups were evaluated. Results:After the intervention, the scores of the Self-efficacy Scale for Self-care in the observation group were higher than those in the control group, and the difference was statistically significant [ (71.03±1.97) vs. (57.82±2.58), P<0.01]. The enamel demineralization rate, periodontal health index (plaque index, gingival index, sulcus bleeding index, probing depth) score, and restart rate in observation group were all lower than those in control group ( P<0.05) . Conclusions:Persuasion system system-based health intervention can improve the oral care self-efficacy of orthodontic patients treated with clear aligners, alleviate oral health issues during clear aligners, and reduce the restart rate of clear aligner patients.

Objective:To explore the effect of persuasion system-based health intervention in orthodontic patients treated with clear aligners.Methods:From January 2022 to December 2023, convenience sampling was used to select patients treated with clear aligners at the Department of Orthodontics in Affiliated Stomatological Hospital of Nanjing Medical University as participants. Patients admitted from January to December 2022 were included in the control group ( n=60), and those admitted from January to December 2023 were included in the observation group ( n=59). The control group received health guidance based on the theory of knowledge, attitude, and practice. Based on the control group, the observation group added health intervention with the assistance of a persuasion system. After one year of intervention, the oral care self-efficacy, enamel demineralization, periodontal health index (gingival index, plaque index, sulcus bleeding index, probing depth), and restart rate of both groups were evaluated. Results:After the intervention, the scores of the Self-efficacy Scale for Self-care in the observation group were higher than those in the control group, and the difference was statistically significant [ (71.03±1.97) vs. (57.82±2.58), P<0.01]. The enamel demineralization rate, periodontal health index (plaque index, gingival index, sulcus bleeding index, probing depth) score, and restart rate in observation group were all lower than those in control group ( P<0.05) . Conclusions:Persuasion system system-based health intervention can improve the oral care self-efficacy of orthodontic patients treated with clear aligners, alleviate oral health issues during clear aligners, and reduce the restart rate of clear aligner patients.

Objective:To investigate the effects of Wumei-Fangfeng drug on Treg/Th17 immune balance in allergic rhinitis(AR)mice via regulating MMP9 derived from mast cell exosomes.Methods:Potential targets of Wumei and Fangfeng were screened,and the intersection was taken from the targets and AR risk genes,subsequently GO analysis and protein-protein interaction analysis were performed to screen therapeutic targets.AR mice model were constructed,mast cells and exosomes were separate from femurs of mice.Wumei-Fangfeng drug and exosomes were used to treat mice.The behavioral scores of mice in each group were evaluated,mRNA expressions of Foxp3,RORγt were detected in nasal mucosa of mice.After knocking down of MMP9 in exosomes,the behavioral score,Foxp3 and RORγt mRNA expressions were observed in AR mice.Results:Bioinformatics results showed that Wumei-Fangfeng drug may act on AR by mast cell exosomes derived IL-1β and MMP9.Compared with normal mice,mRNA expression of Foxp3 in AR mice was decreased,while RORγt mRNA expression was increased,and MMP9 expression was increased(all P<0.05).Expression of Foxp3 mRNA was increased,and expressions of RORγt and MMP9 were decreased in AR mice treated with Wumei-Fangfeng drug,however,mast cell exosomes could further counteract the effects of Wumei-Fangfeng drug,and the effects of mast cell exosomes was weakened after MMP9 knockdown.Conclusion:Wumei-Fangfeng drug regulates the imbalance of Treg/Th17 in AR mice by inhibiting the exosomal MMP9 of bone marrow-derived mast cells.

Objective To investigate the differences in treatment experience and quality of life between adolescent orthodontic pa-tients using clear aligners and fixed braces.Methods A total of 104 adolescent patients were selected who underwent orthodontic treat-ment with either clear aligners or fixed braces at Nanjing Medical University Affiliated Stomatological Hospital from January 2022 to June 2022.The patients were divided into two treatment groups based on the type of orthodontic appliance,with 52 patients in each group.Within a 6-month period of using clear aligners or fixed braces,adolescent orthodontic patients were surveyed using the child oral health impact profile-short form 19(COHIP-SF19)and other individual items.The differences in mean satisfaction,quality of life,and statistical scores were compared using independent samples t-tests,while the differences in subjective responses were compared using the Wilcoxon rank-sum test.Results There were no significant differences in mean quality of life and statistical scores between the two groups,but patients in the clear aligner group reported higher satisfaction.The clear aligner group reported greater difficulty with eating,while patients with fixed braces were more likely to experience negative emotions.Additionally,there were no significant differences between the two groups in terms of adaptation time to the appliance,maintaining dental hygiene,and feeling attractive.Conclusion Patients in both groups were generally satisfied with their treatment.Adolescent orthodontic patients treated with clear a-ligners or fixed braces for at least 6 months exhibit similar overall quality of life.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.