Objective To investigate the population density and seasonal fluctuations of Aedes albopictus in Guangzhou City, Guangdong Province, from 2021 to 2023, so as to provide insights into A. albopictus control and management of dengue fever. Methods The surveillance of A. albopictus density was performed in all surveillance sites assigned across all streets (townships) in Guangzhou City during the period from January to December from 2021 to 2023. The surveillance frequency was twice every half month from May to September, and once every month for the rest of a year. In each surveillance period, A. albopictus mosquito larvae were captured from indoor and outdoor small water containers in residential areas, parks, medical facilities, schools, other government sectors and social organizations, construction sites, special industries and others for mosquito species identification. Adult mosquitoes were captured using electric mosquito suction apparatus for species identification and gender classification. Adult mosquitoes and mosquito eggs were collected with mosquito and egg traps at the breeding and dwelling places of Aedes mosquitoes for identification. The mosquito oviposition index (MOI), Breteau index (BI), adult mosquito density index (ADI) and standard space index (SSI) were calculated. The A. albopictus density was classified into grades 0, 1, 2 and 3 in each surveillance site, with Grade 0 density defined eligible, and the eligible rate of A. albopictus density was calculated at all surveillance sites each year from 2021 to 2023. In addition, the changing trends in MOI, SSI, BI and ADI of A. albopictus were analyzed in Guangzhou City from 2021 to 2023. Results The eligible rates of A. albopictus density were 61.69%, 68.75% and 55.15% in surveillance sites of Guangzhou City from 2021 to 2023 (χ² = 297.712, P < 0.001), and appeared a tendency towards a reduction followed by a rise each year, which gradually reduced since January, maintained at a low level during the period between May and October, and gradually increased from November to December. The MOI, SSI, BI and ADI of A. albopictus all appeared a tendency towards a rise followed by a reduction in Guangzhou City during the period between January and December from 2021 to 2023. The BI of A. albopictus peaked in the first half of June in 2021 (4.03), the first half of July in 2022 (3.89) and the last half of August in 2023 (5.02), and the SSI of A. albopictus peaked in the last half of June in 2021 (0.93), the last half of May in 2022 (0.59), and the last half of June (0.94) and the first half of September in 2023 (1.12). In addition, the MOI of A. albopictus peaked in the first half of May in 2021 (8.64), the first half of June in 2022 (8.96), and the last half of May (10.21) and the last half of June in 2023 (10.89), and the ADI of A. albopictus peaked in the first half of June in 2021 (3.41), the last half of June in 2022 (4.06), and the first half of July in 2023 (3.61). Conclusions The density of A. albopictus is high in Guangzhou City during the period from May to October, and the risk of local outbreak caused by imported dengue fever is high. Persistent intensified surveillance of the density and seasonal fluctuation of A. albopictus is recommended and timely mosquito prevention and control is required according to the fluctuation in the A. albopictus density.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective: To analyze the trend of the incidence of pulmonary tuberculosis in Yecheng County of Xinjiang from 2011 to 2022 and the influence of age, period and birth cohort effect on the incidence of pulmonary tuberculosis, so as to provide a new theoretical reference for the prevention and control of local pulmonary tuberculosis. Methods : Based on the registration data of new pulmonary tuberculosis cases in Yecheng County, Xinjiang from 2011 to 2022, the connection point regression model was used to calculate the crude incidence rate, age-standardized incidence rate, annual percentage change(APC), and average annual percentage change(AAPC) to describe the epidemic trend of pulmonary tuberculosis. The age-period-cohort model was used to explore the influence of age, period and birth cohort effect on the trend of pulmonary tuberculosis incidence. Results : From 2011 to 2022, a total of 17 057 new cases of pulmonary tuberculosis were registered in Yecheng County, Xinjiang. The crude incidence and standardized incidence were 416.07/100 000 and 496.01/100 000, respectively. The incidence of pulmonary tuberculosis increased first and then decreased during the 12 years, with an upward trend from 2011 to 2018. The APC values of the standardized incidence of pulmonary tuberculosis in the total population, males and females were 24.42%(95%CI: 11.55-38.78), 27.24%(95%CI: 12.35-44.10) and 21.79%(95%CI: 9.81-35.09), respectively. From 2018 to 2022, there was a downward trend. The APC values of the standardized incidence of tuberculosis in the total population, males and females were-38.51%(95%CI:-53.27--19.09),-38.18%(95%CI:-54.59--15.85) and-38.73%(95%CI:-52.96--20.19), respectively. With the increase of age, the incidence of pulmonary tuberculosis showed a trend of rising first and then fluctuating steadily. The risk of the population increased first and then decreased over time, and the later the birth, the lower the risk of the cohort. Conclusion The incidence of pulmonary tuberculosis in Yecheng County of Xinjiang showed a trend of increasing first and then decreasing in the past 12 years, and gradually increased with age. The earlier the birth, the higher the risk of the disease. Men and the elderly are the key targets of tuberculosis prevention and control in Yecheng County, Xinjiang. It is recommended to strengthen the screening of key populations.

Objective : To explore the feasibility of machine learning methods in the discrimination of tuberculosis patients. Methods : The data of 15 observation indicators of 860 patients were obtained from a tertiary hospital. Through in-depth mining and analysis of the data, support vector machine, random forest and neural network model methods were used to discriminate the diseases of patients. Results : The accuracies of the TB suspected patient discrimination models based on support vector machine, random forest and neural network were 90%, 91% and 88%, respectively. Conclusion All three machine learning methods can be used for discriminative analysis of suspected tuberculosis patients. In comparison, random forest performs better in discriminating patients with tuberculosis from those with pneumonia.

Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR-insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

ObjectiveTo construct the evidence body for revision of safety information on package inserts of Chinese patent medicines in post-marketing by taking Xiaoke'an capsules as an example， so as to provide reference for the revision of instructions of Chinese patent medicines in post-marketing. MethodThe construction of the evidence body was guided by the theory of traditional Chinese medicine（TCM） and the Technical Guiding Principles for Revision of Safety Information Items in Instructions for TCMs After Marketing， and 8 categories and 25 specific items were taken as the main body of the evidence body， and information inclusion， integration， screening and improvement were carried out， then expert demonstrations were conducted， and finally modifications were made based on the opinions of the Center for Drug Evaluation to complete the revision of the safety information in the instructions of Xiaoke'an capsules. Result［Adverse reactions］ of Xiaoke'an capsules was revised to "monitoring data show that the following adverse reactions can be seen with this product：individual hypoglycemic reaction reports". ［Contraindications］ was revised to "contraindicated for those allergic to this product and its ingredients". ［Precautions］ was revised to "（1）pregnant women should use with caution， （2）elderly people should consult a physician， （3）people with spleen deficiency and dampness， spleen and stomach deficiency and cold， or those who eat less and have diarrhea should use with caution， （4）this product contains ginseng， should not be taken at the same time with TCM prescriptions or patent medicines containing veratrum and Wulingzhi， （5）pay attention to monitoring blood sugar during medication， （6）if any other discomfort occurs during medication， you should seek medical attention in time". The warning was revised to "use with caution by pregnant women， and pay attention to regular monitoring of blood sugar". ConclusionIn accordance with the content and process of the evidence body for the revision of safety information in the instructions， the revision of the safety information in the instructions of Xiaoke'an capsules has been completed， providing a strong basis for the rational and safe use of medication in the clinic.

With the rapid development of the interdisciplinary area of artificial intelligence and medicine, large language model (LLM) has been widely used in the fields such as diagnosis and treatment, medicine, and healthcare. LLM has unique advantages in the field of traditional Chinese medicine (TCM), such as high consistency with the "Four Diagnostic Methods", perfect combination of natural language and self-supervised learning in TCM, the ability to adapt to the characteristics TCM formulas, and the assistance in TCM diagnosis and treatment. At present, various LLM models have been developed, including the "Qihuang Ask Big Model" and the Digital Traditional Chinese Medicine Big Model "GLM-130B", but they still face challenges such as value mismatch and medical abuse, increased demand for interpretability, lack of advanced technology, and domestic policy access. This article reviews the evolution of LLM, its unique advantages and applications in the field of TCM, the problems and challenges, and the future development trends, in order to providereference for the further promotion of LLM in traditional medicine.

"Target trial emulation" (TTE), as a new framework in real-world research, has been formally established in recent years. It can be used to guide the evaluation of the effectiveness and safety of medical interventions based on real-world data for observational causal inference. The core idea of this framework is to follow the principles of randomized controlled trial (RCT), emulate a corresponding RCT using real-world data, and then draw conclusions about the causal relationship between interventions and outcomes. The main implementation tips of TTE can be summarized as "3-7-2": 3 implementation steps including formulating the causal question, designing the emulation plan, and emulating the target study; 7 design elements including eligibility criteria, treatment strategies, intervention allocation, follow-up period, outcome, causal contrast of interest, and analysis plan; and control of 2 critical biases including immortal time bias and prevalent user bias. In this article, we present an overview of the development, current status, implementation steps, classic examples, advantages and limitations of TTE, and its application prospects in traditional Chinese medicine (TCM). It is hoped that this article can assist researchers in TCM to utilize this method for real-world research and contribute to the construction of a clinical evaluation system with distinctive features of TCM.

BACKGROUND:Anterior subtotal corpectomy,decompression and fusion is a conventional method to treat cervical degenerative diseases.A titanium cage is an important implant to maintain the stability of the cervical spine after subtotal corpectomy.In recent years,many patients have complications such as titanium cage sinking,which are highly controversial. OBJECTIVE:To investigate the internal biomechanical relationship between the tilt angle of the titanium cage and postoperative titanium cage subsidence after anterior subtotal cervical corpectomy,decompression and fusion. METHODS:A three-dimensional finite element model of the C4-C6 segment was established by CT images of a normal human cervical spine,in which the anterior subtotal resection,decompression and fusion of the C5 vertebral body were simulated,and titanium cages with different tilt angles(-6° to-1° negative angle,that is,the front edge of titanium cage is shorter than the rear edge of titanium cage;1° to 6° positive angle,that is,the front edge of titanium cage is longer than the rear edge of titanium cage)were placed.After setting the boundary conditions,preloads of 50,100 and 150 N were applied respectively on the C4 vertebral body.The stress value of each contact point between the titanium cage and C4 lower-end plate and C6 lower-end plate(seven stress contact points on the contact surface of titanium mesh)was recorded and statistical analysis was conducted. RESULTS AND CONCLUSION:(1)The tilt angles of the titanium cage of the positive angle group and negative angle group under 50,100 and 150 N stress respectively were found by Mann Whitn test,with P<0.05,which was statistically significant.The dispersion coefficients of the positive angle group were smaller than those of the negative angle group under 50,100 and 150 N stress conditions.(2)Under 50,100 and 150 N stress conditions,the Wilcoxon sign rank test in the positive angle group of titanium cage tilt angle found that when the angle was set to 1° to 5°,the difference was not statistically significant(P>0.05).However,when the tilt angle of the titanium cage was set to 6°,the difference was statistically significant(P<0.05).(3)Under 50,100 and 150 N stress conditions,the Wilcoxon sign rank test in the negative angle group of titanium cage tilt angle found that when the tilt angle was set to-1° to-6°,the difference was not statistically significant(P>0.05).(4)It is concluded that in the sagittal position,the titanium cage with a positive tilt angle is more stable than with a negative tilt angle,which is more suitable for clinical use.The tilt angle of the titanium cage is relatively stable in the range of 1° to 5°.When the tilt angle is 6°,the stability starts to decline,which is easy to cause complications of titanium cage sinking after surgery.It is more suitable to select the titanium cage with a tilt angle of 1° to 5° according to the clinical situation during surgery to improve the efficacy.

BACKGROUND:Cervical spondylotic myelopathy is a progressive disease leading to dysfunction in the middle-aged and elderly,and early diagnosis is difficult.In recent years,some clinical scholars have found that dynamic magnetic resonance imaging technology can detect spinal cord compression in a dynamic position earlier,but its specific biomechanical mechanism needs to be clarified. OBJECTIVE:To investigate the biomechanical compression characteristics of early cervical spondylotic myelopathy in hyperextension and flexion position,and to verify the effectiveness of dynamic magnetic resonance imaging in the diagnosis of early cervical spondylotic myelopathy. METHODS:A retrospective analysis was made on the patients who underwent cervical dynamic magnetic resonance imaging in the Department of Orthopedics of First Affiliated Hospital of Guangxi University of Chinese Medicine from January to June 2022.16 subjects were selected and divided into two groups.The pathological group included 8 patients with early cervical spondylotic myelopathy with hypertrophy of ligamentum flavum as the main sign,with 5 male patients and 3 female patients.The normal group included 8 normal degenerative people,with 4 male patients and 4 female patients.All patients were photographed with cervical CT plain scan,magnetic resonance imaging plain scan,and dynamic magnetic resonance imaging plain scan.This study was divided into the following three parts:(1)collect the dynamic magnetic resonance imaging image DCOM data of two groups of subjects,and collect the cervical vertebra CT and neutral magnetic resonance imaging image DCOM data to understand the bone and soft tissue of the two groups of subjects in the neutral position.(2)Based on the DCOM data of magnetic resonance imaging and CT plain scan,the three-dimensional finite element models of lower cervical vertebra(C3-7)of normal degenerative population and early cervical spondylotic myelopathy patients were established by reverse engineering software.The equivalent stress and equivalent elastic strain of the spinal cord and posterior dura were analyzed,and the distribution of stress and strain was observed.(3)After obtaining the stress and strain data,the data between groups were compared to analyze the mechanical characteristics of spinal cord compression caused by early cervical spondylotic myelopathy in a dynamic position and to verify the effectiveness of dynamic magnetic resonance imaging in the diagnosis of early cervical spondylotic myelopathy. RESULTS AND CONCLUSION:(1)When simulating the posterior extension,flexion and neutral position of the lower cervical vertebrae(C3-7)in the two groups,the values of stress and strain in the posterior part of the spinal cord were in the following order:extension>flexion>neutral(P<0.05).The strain values from large to small were as follows:extension>flexion>neutral(P<0.05).(2)Compared with the normal degenerative population model,the equivalent stress and strain of the spinal cord in the pathological group were higher than those in the normal group under two degrees of freedom of flexion and extension(P<0.05).The distribution area of stress and strain in the posterior part of the spinal cord was irregular.(3)In the neutral position,there was no significant difference in the strain value of the spinal cord between the two groups(P>0.05),and the strain distribution was uniform and regular.(4)It is indicated that in the cervical extension position,the dural sac and the posterior part of the spinal cord were compressed and deformed in the early cervical spondylotic myelopathy patients with the hypertrophy of ligamentum flavum as the main sign,and the degree of compression deformation of the spinal cord was significantly higher than that in the anterior flexion position and neutral position.In the neutral position,there were no obvious signs of spinal cord deformation in patients with early cervical spondylotic myelopathy.This study verified the role of dynamic magnetic resonance imaging in the diagnosis of early cervical spondylotic myelopathy from the point of view of biomechanics.