Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Objective: To examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes. Methods: The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model. Results: A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915). Conclusion The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease characterized by structural or functional abnormalities of motile cilia. It often presents clinically with recurrent respiratory infections, situs inversus, hydrocephalus, and infertility. Currently, there is no clinical treatment to directly restore ciliary motility in PCD patients.In recent years, researchers have explored gene therapy methods such as gene replacement, gene editing, and RNA replacement in vitro and in mouse models, offering potential new strategies for PCD treatment. This paper comprehensively reviews the current status of PCD gene therapy research, evaluates the potential of different gene therapies, and provides an outlook on the future treatment directions for this disease.

Objective: To investigate the trajectories of fasting blood glucose fluctuations and their influencing factors among patients with comorbidity of type 2 diabetes mellitus (T2DM), so as to provide the basis for strengthening blood glucose management in this population. Methods: In October 2023, data of patients diagnosed with comorbid T2DM from January to October 2021, including demographic information, lifestyle, health status and fasting blood glucose were collected through the chronic disease health management system of Minhang District, Shanghai Municipality. Fasting blood glucose fluctuation trajectories were analyzed by group-based trajectory model established based on fasting blood glucose values from January 2021 to October 2023. Influencing factors of fasting blood glucose fluctuation trajectories among patients with comorbidity of T2DM were analyzed using a multinomial logistic regression model. Results: A total of 907 patients with comorbidity of T2DM were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged ≥65 years, accounting for 71.89%. The group-based trajectory model analysis identified three trajectory groups: a low-level stable group (492 cases, 54.24%), a medium-level stable group (287 cases, 31.64%), and a high-level decreasing group (128 cases, 14.11%). Multinomial logistic regression analysis showed that, compared with the low-level stable group, patients with comorbidity of T2DM who had an education level of junior high school or below (OR=1.420, 95%CI: 1.011-1.995) or college degree or above (OR=2.109, 95%CI: 1.249-3.560), as well as those who engaged in regular exercise (OR=1.387, 95%CI: 1.017-1.893), were more likely to be in the medium-level stable group. Patients with comorbidity of T2DM who were overweight or obese (OR=1.675, 95%CI: 1.116-2.513) or had dyslipidemia (OR=3.195, 95%CI: 1.642-6.216) were more likely to be in the high-level decreasing group. Conclusions From January 2021 to October 2023, the fasting blood glucose levels of patients with comorbidity of T2DM exhibited three fluctuating trajectories: low-level stability, medium-level stability, and high-level decline. Compared with the low-level stable group, the medium-level stable group was mainly influenced by educational level and regular exercise. The high-level decline group was primarily affected by overweight/obesity and dyslipidemia.

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Liver diseases have become a major challenge threating the global health, posing a heavy burden on both social and personal well-being. In recent years, the development of the gut-liver axis theory has provided new research perspectives and intervention strategies for the prevention and treatment of liver diseases. Natural products, recognized as biological molecules with diverse sources, rich activities, and minimal side effects, demonstrate great potential in regulating intestinal flora and improving liver health. Studies have shown that natural products such as saponins, polyphenols, polysaccharides, and alkaloids can regulate the composition and metabolites of intestinal flora, thereby intervening in liver diseases. In this paper, we systematically review the role of natural products in the regulation of the intestinal flora-gut-liver axis and summarize recent research progress in the prevention and treatment of liver diseases. Furthermore, we outline the challenges and limitations currently facing the study in this field. Finally, this paper makes an outlook on the clinical application of natural products in treating liver diseases and discusses future research directions, aiming to give new insights into the mechanisms by which natural products regulate the intestinal flora-gut-liver axis and the applications of these products in the prevention and treatment of liver diseases.
Humans ; Gastrointestinal Microbiome/drug effects* ; Liver Diseases/prevention & control* ; Biological Products/pharmacology* ; Polyphenols/pharmacology* ; Saponins/pharmacology* ; Intestines/microbiology* ; Alkaloids/pharmacology* ; Polysaccharides/pharmacology* ; Liver

ObjectiveTo observe the effects of Agrimoniae Herba and Coptidis Rhizoma（XHC-HL） on the proliferation， migration， invasion， apoptosis， and autophagy of colorectal tumor cells and explore the mechanism of Agrimoniae Herba and Coptidis Rhizoma in inhibiting colorectal cancer by regulating chaperone-mediated autophagy（CMA）. MethodXHC-HL-containing serum was prepared， and human colorectal cancer cell lines HT29 and LOVO were cultivated and divided into blank group （20% blank serum）， low XHC-HL groups （5%， 10%， 20% drug-containing serum）， and a positive control group using 5-fluorouracil （5-FU）. Cell viability was measured using the cell counting kit-8 （CCK-8） method. Cell proliferation ability was assessed through 5-ethynyl-2′-deoxyuridine （EdU） staining. Scratch assays and Transwell migration tests were conducted to evaluate cell migration ability， and Transwell invasion assays were used to assess cell invasion ability. Apoptosis rates were determined by flow cytometry， and the impact of XHC-HL on yeast Atg6 homologous 1 （Beclin-1）， microtubule-associated protein1 light chain3 Ⅱ （LC3 Ⅱ）， and p62 was analyzed via Western blot. The influence of XHC-HL on CMA-related proteins and mRNA was examined using Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared to that in the blank group， the vitality of colorectal cancer cells HT-29 and LOVO was significantly inhibited in XHC-HL groups and the 5-FU group （P<0.01）. Compared to that in the blank group， the proliferation of colorectal cancer cells HT-29 and LOVO was significantly inhibited in XHC-HL groups and the 5-FU group （P<0.05， P<0.01）. Compared to the blank group， there was a significant reduction in cell migration rates （P<0.01）， the number of cells migrating to the lower chamber （P<0.01）， and the number of invasive cells （P<0.01）， as well as and an increase in cell apoptosis （P<0.01） in XHC-HL groups and the 5-FU group （P<0.01）. Western blot results indicated that compared to that in the blank group， the expression levels of Beclin-1 and LC3 Ⅱ were increased（P<0.05，P<0.01）in XHC-HL groups and the 5-FU group， while the p62 levels were decreased（P<0.05，P<0.01）. Furthermore， the protein expression levels of lysosomal associated protein 2A （LAMP2A）， heat shock cognate protein 70 （HSC70）， and heat-shock protein 90 （HSP90） in XHC-HL groups and the 5-FU group were decreased to varying extents， whereas the expression levels of glyceraldehyde-3-phosphate dehydrogenase （GAPDH） were elevated （P<0.01）. The Real-time PCR results showed that compared to those in the blank group， the mRNA levels of LAMP2A， HSC70， and HSP90 were downregulated in XHC-HL groups and the 5-FU group， and the mRNA expression level of GAPDH was upregulated （P<0.01）. ConclusionXHC-HL can inhibit the proliferation， migration， and invasion of colorectal cancer cells by suppressing CMA activity， thus inducing autophagy and promoting apoptosis.

Objective:To understand the characteristics of sexual behaviors in the elderly aged ≥60 years and provide evidence for AIDS prevention and control in the elderly.Methods:Local residents who were aged ≥60 years and had lived in Yongchuan District of Chongqing for more than half a year were recruited by multi-stage sampling with a sample size of 2 721 from September to December 2022 for a face to face questionnaire survey to collect the information about their demographic characteristics, awareness of AIDS related knowledge and sexual behaviors, and the incidence of non-marital sexual behaviors. Multivariate logistic regression model was used to analyze related factors non-marital sexual behaviors in the elderly aged ≥60 years. SPSS 23.0 software was used for statistical analysis.Results:A total of 2 974 valid questionnaires were collected from 3 000 old persons aged ≥60 years, the male to female ratio of the elderly who returned the questionnaires was about 1∶1 (1 488∶1 486). The average age of them was (69.3± 7.0) years, and the awareness rate of AIDS related knowledge was 78.5% (2 336/2 974), 26.9% of them (801/2 974) had sexual behavior in the past year, 20.9% (493/2 350) of them had sexual behaviors with their spouses in the past year, and 10.8% (322/2 974) of them had non-marital sexual behaviors. The proportions of the elderly with commercial sexual behaviors and non-marital/non-commercial sexual behaviors were 10.2% (304/2 974) and 1.2% (36/2 974). The results of multivariate logistic regression analysis showed that being man (a OR=89.08, 95% CI: 36.30-218.60), age 70-79 years (a OR=1.93, 95% CI:1.44-2.59) and ≥80 years (a OR=2.41, 95% CI: 1.56-3.74), and unawareness of AIDS related knowledge (a OR=2.72, 95% CI: 2.04-3.64) were associated with the incidence of non-marital sex. Conclusions:The proportions of non-marital sexual behaviors were higher among the elderly aged ≥60 years in Yongchuan District of Chongqing. It is necessary to pay attention to the sexual needs and sexual health of the population, improve the awareness rate of AIDS prevention and treatment knowledge, advocate safe sex, and improve the sexual health and quality of life in the elderly.

This study investigated the primary pathogenesis and syndrome evolution of different heart failure with preserved ejection fraction(HFpEF)stages based on the classical and clinical experience of traditional Chinese medicine(TCM),combined with the clinical characteristics of pre-heart failure,symptomatic heart failure,and advanced heart failure.This study summarizes and refines the three core syndrome factors:water,deficiency and blood stasis.Water-fluid retention was observed throughout these three stages,from the beginning to the end.With the advancement of the disease,the heart yang changes from stagnation to deficiency,water-fluid retention gradually increases,blood stasis becomes increasingly prominent,and the disease location develops dynamically from the upper to the middle and lower jiao.This study proposes three methods of treating HFpEF.The main pathogenesis of pre-heart failure is lung qi dysfunction-induced water retention,which can be treated by dispersing lung qi and transforming water retention using Fuling Xingren Gancao Decoction.The primary pathogenesis of symptomatic heart failure is yang and qi deficiency-induced water retention,which can be treated with tonifying yang,supplementing qi,and transforming water retention using Shengxian Decoction combined with Linggui Zhugan Decoction.The primary pathogenesis of advanced heart failure is yang deficiency with blood stasis and water retention affecting the heart,which can be treated with tonifying yang,circulating blood,and expelling water retention using Zhenwu Tingli Decoction.Chinese medicine can be flexibly added or subtracted according to the patients'concurrent patterns.However,the daily care of patients should be considered.This study explores the staging treatment of HFpEF from water,deficiency and blood stasis to provide a TCM clinical reference for treating HFpEF.

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.