Parkinson's disease （PD） is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra， abnormal aggregation of alpha-Synuclein （α-Syn）， and the formation of Lewy bodies. However， the exact mechanisms remain unclear. In recent years， the PD incidence has gradually increased， while current treatment methods are limited to symptom alleviation， incapable of halting disease progression， and prone to adverse effects， thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is closely related to oxidative stress， neuroinflammation， apoptosis， ferroptosis， and mitochondrial dysfunction， playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine （TCM） can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages， such as multiple targets， multiple pathways， and fewer adverse reactions， TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD， while summarizing the latest research on PD intervention by TCM monomers， active ingredients， and compounds， as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway， aiming to provide a reference for clinical medicine development to prevent and treat PD.

Objective To compare the long-term prognosis of elderly patients with stageⅠnon-small cell lung cancer (NSCLC) after lobectomy or segmentectomy. Methods Data of elderly patients with stageⅠNSCLC between 2010 and 2020 were collected from the SEER database. According to the resection method, patients were divided into a lobectomy group and a segmentectomy group. The overall survival (OS) and lung cancer-specific survival (LCSS) of the two groups were compared by propensity score matching (lobectomy : segmentectomy=2 : 1). Results A total of 9990 patients were included, including 5840 (58.46%) females and 4150 (41.54%) males, with an average age of (70.48±6.47) years. Among them, 9029 patients were in the lobectomy group and 961 patients were in the segmentectomy group. After propensity score matching, a total of 2883 patients were matched, including 1 922 patients in the lobectomy group and 961 patients in the segmentectomy group. There was no statistical difference in baseline data between the two groups (P>0.05). The 10-year OS rate and LCSS rate of the lobectomy group were higher than those of the segmentectomy group (OS: 51.15% vs. 38.35%, P<0.01; LCSS: 79.68% vs. 71.52%, P<0.01). Subgroup analysis showed that the survival advantage of lobectomy was found in patients aged 60-<70 years and ≥80 years; for patients 70-<80 years, there was no statistical difference in OS or LCSS between the two surgical methods (P>0.05). In addition, for patients with tumor diameter ≤2 cm (stages ⅠA1-ⅠA2), lymph node dissection number≥10, and receiving adjuvant radiotherapy/chemotherapy, segmentectomy could also achieve a similar prognosis as lobectomy. Conclusion Overall, for elderly patients with stage ⅠNSCLC, lobectomy can achieve better OS and LCSS. However, individual differences, tumor characteristics, and perioperative treatment plans should be considered comprehensively to determine the surgical method for elderly patients with stageⅠNSCLC.

Objective: To explore the clinical characteristics and diagnosis and treatment plans of neurofibromatosis type 1 (NF1), and to provide references for clinical diagnosis and treatment. Methods : The clinical manifestations and treatment of an 8-year-old female patient with NF1 was reported. A literature review was conducted to summarize the clinical characteristics and therapeutic strategies of NF1. Multiple NF1s occurred on the right cheek, orbit, and eyelid, and recurred after surgical resection. The tumor caused ptosis, incomplete closure, and vision loss in the upper eyelid of the right eye. After a multidisciplinary assessment determined that radical resection was not feasible, selumetinib sulfate targeted therapy was adopted (25 mg, Po, bid), 28 days constitute one treatment course, and 14 courses have been completed, combined with symptomatic ocular treatments, such as Befusu. Result: The follow-up showed that the tumor volume did not continue to increase (stable disease), the uncorrected vision of the right eye improved (0.05 vs 0.1), and no drug-related adverse reactions occurred during the treatment period. The literature review summarizes the diverse clinical manifestations of NF1, with café-au-lait macules, multiple neurofibromas, and Lisch nodules being hallmark features. Currently, surgical intervention remains the most commonly employed and primary therapeutic approach for NF1; however, for patients who do not meet the criteria for surgery, alternative treatment strategies should be considered. MEK inhibitors, such as selumetinib, demonstrate significant efficacy in inhibiting the growth of NF1-associated plexiform neurofibromas, with tumor volume reductions of at least 20% observed in 70% of pediatric patients in the SPRINT clinical trial. Furthermore, these inhibitors exhibit favorable long-term safety profiles. Conclusion Café-au-lait macules, multiple neurofibromas, and Lisch nodules are hallmark features of NF1. Selumetinib is safe and effective for NF1 in the head and neck of children, and it is the preferred treatment option for patients who are not suitable for surgery. Long-term follow-up monitoring of tumor changes and drug safety is required.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

It is regarded that the general qi is the combination of spleen-kidney qi and heart-lung yang qi in the chest， which is filled between the muscles and is able to maintain the normal shape of the muscles. Accordingly， it is proposed that the core pathogenesis of amyotrophic lateral sclerosis （ALS） is the deficiency sinking of general qi， with "deficiency" as the root， and "toxin" and "wind-heat" as the key factors for the rapid progression of the disease. The development process of ALS was classified into the initial onset stage， the increasingly progressive stage， and the rapid exacerbation stage， and differentiated and treated by deficiency， toxin， and wind-heat. Based on clinical experience， the wind medicinals were preferred. We formed self-prescribed Juxian Decoction （举陷汤） and modified from the perspective of "deficiency， toxicity， wind-heat" based on the wind medicinals of Huangqi （Radix Astragali）， Shengma （Actaea cimicifuga L.）， Chaihu （Bupleurum spp.） and so on. For the initial onset stage， Yiqi Shengji Juxian Decoction （益气生肌举陷汤）， Wenyang Liyan Juxian Decoction （温阳利咽举陷汤） could be used； for the increasingly progressive stage， Jiedu Juxian Decoction （解毒举陷汤） could be used； for the rapid exacerbation stage， Yinqiao Shufen Juxian Decoction （银翘疏风举陷汤）， Yangxue Xifeng Juxian Decoction （养血熄风举陷汤） could be used.

Post-stroke depression is a common complication after a stroke. Based on the theory of ＂deficiency of heart qi leading to sadness＂recorded in Huangdi Neijing, our team proposes that deficiency of heart qi is the basic pathogenesis of post-stroke depression, with sadness being its main manifestation. Therefore, we advocate treating post-stroke depression from the perspective of the heart, and clinically, it can be divided into four stages: heart-liver stage, heart-lung stage, heart-spleen stage, and heart-kidney stage. Treating post-stroke depression with the principle of regulating qi and nourishing the heart, patients in the heart-liver and heart-lung stages are mainly middle-aged and young adults, with a pathological nature of qi stagnation and mild deficiency of heart qi, and therefore, the method of promoting the flow of meridians and regulating qi should be adopted. In contrast, patients in the heart-spleen and heart-kidney stages are mainly middle-aged and elderly, with a pathological nature of qi deficiency and severe deficiency of heart qi, and therefore, nourishment and tonification should be prioritized. In response to the above four stages, our team has achieved good clinical efficacy by administering Xiaoyao Powder, Baihe Dihuang Decoction, Ganmai Dazao Decoction and Jingui Shenqi Pill respectively. This study discusses the approach to treating post-stroke depression from the perspective of a "deficiency of heart qi leading to sadness" by examining three aspects: the theoretical basis of Chinese and Western medicine to treat post-stroke depression from the heart, the basic pathogenesis and staging of post-stroke depression, and the treatment principle of regulating qi and nourishing the heart. The study also briefly analyzes the clinical experience of the medications used for this condition to provide a reference for the treatment of post-stroke depression.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

Alternative polyadenylation(APA)is a crucial step in post-transcriptional regulation.Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites(PASs)in a given genomic sequence,which is a binary classification problem.Recently,computa-tional methods for predicting the usage level of alternative PASs in the same gene have been pro-posed.However,all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account.To address this,here we propose a deep learning architecture,Deep Regulatory Code and Tools for Alternative Polyadenylation(DeeReCT-APA),to quantitatively predict the usage of all alternative PASs of a given gene.To accommodate different genes with potentially different numbers of PASs,DeeReCT-APA treats the problem as a regression task with a variable-length target.Based on a convolutional neural network-long short-term memory(CNN-LSTM)architecture,DeeReCT-APA extracts sequence features with CNN layers,uses bidirectional LSTM to explicitly model the interactions among com-peting PASs,and outputs percentage scores representing the usage levels of all PASs of a gene.In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene,we show that our method consistently outperforms other existing methods on three different tasks for which they are trained:pairwise comparison task,highest usage prediction task,and rank-ing task.Finally,we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation.

Objective:To evaluate the frailty status, and to explore its related factors among the community-dwelling elderly people in Beijing, so as to provide scientific basis for taking corresponding measures to delay the frail process of the elderly.Methods:From November 2015 to January 2016, a cross-sectional study was performed among elderly adults of Longtan Community in Dongcheng District, Beijing.Persons aged 60 years and over were selected using a stratified cluster sampling method, and the geriatric frailty-related information was collected through face-to-face household interview.The frailty index(FI)was used to evaluate the frailty status.Multivariate linear regression analysis was used to explore influencing factors on FI value among the elderly.Results:Of the 1 557 interviewees, the median(quartile)value of FI was 0.09(0.08); and women had a higher FI median value than men[0.10(0.08) vs.0.08(0.07)]( Z=5.376, P=0.000). The FI value increased with age( H=329.698, P=0.000). In addition, multivariate linear regression analysis showed that female, older age, disability, being hospitalized in the previous year, being hospitalized during the past 3 years, being unsatisfied to living conditions had relatively higher FI value than the control group( β=0.082, 0.236, 0.336, 0.065, 0.089, 0.193, all P<0.05); and people with high education level, family harmony, a large number of friends who gave support and help, more frequency of participating in organization activities, regular physical examination, and routine exercise had lower FI value than the control group( β=-0.049, -0.052, -0.089, -0.047, -0.045, -0.219, all P<0.05). For FI value, physiological disability was the greatest influencing factor, followed by ageing and not often physical exercise. Conclusions:Similar to foreign studies, the FI method is an effective method to evaluate the frailty status and characteristics among older adults, and is also applicable for the elderly in China.Frailty in elderly people is related not also to intrinsic factors, such as physiology and disease, but also to interventionable factor, such as society, psychology and behavior.Therefore, comprehensive measures should be adopted to delay the process of frailty among the elderly.

Objective:To analyze the relationship between frailty status and the risk of death in the elderly based on the frailty index (FI).Methods:Data from a prospective cohort study conducted between 2005 and 2015 in elderly people of an urban community in Beijing were analyzed. The variables related to health and frailty status based on the 2005 baseline survey and death as outcome variables collected in 2015 were used. A FI model was used to evaluate the correlation between FI and mortality in the elderly people in different age groups was analyzed. Cox regression was applied to evaluate the influence of FI on the risk of death, and Kaplan-Meier curves was used to show the survival rate of different frailty levels in the elderly adults.Results:Of the 1 301 elderly people included in the analysis, 403 died during 2005-2015, with the 10-year mortality rate of 31.0 %(403/1 301). The mortality rate of the elderly increased with the increase of FI, but, with the increase of FI value, the rate of mortality increased slowly. The limit value of FI causing death was around 0.70, indicating any new health problem might cause death at this value. Cox regression analysis showed that higher FI was associated with higher risk for death ( HR=1.143, 95 %CI: 1.034-1.248, P=0.000), and FI was more significantly associated with death than age ( HR=1.143 vs. HR=1.048, t=5.827, P=0.000). With the increase of age, the effect of frailty on the risk of death decreased ( HR=1.179 to HR=1.120). Kaplan-Meier curves showed that the survival rate of the elderly in all age groups decreased with the increase of frailty (Log-rank=317.812, 354.203, 247.258, all P=0.000). The survival time between different frailty levels in the elderly were significantly different, except for the elderly adults aged ≥80 years with severe frailty level (0.4≤FI<0.5, FI≥0.5, P=0.368). Conclusions:Compared with other evaluation tools of frailty, FI model can better reflect the frailty status of the elderly in communities in Beijing and has a high sensitivity in predicting adverse outcomes such as mortality. In the intervention of frailty in the elderly, focusing on relatively young elderly might be more effective in reducing the adverse outcomes caused by frailty.