This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Objective To analyze the current status and quality of existing obstetrics and gynecology enhanced recovery after surgery(ERAS)guidelines/consensus,understand the evidence-based practices in this field,and provide a basis for clinical decision-making.Methods A systematic search of PubMed,CNKI,and other databases,as well as NGC,SIGN,and websites of anesthesia societies domestically and internationally was conducted to obtain relevant guidelines and consensus on ERAS for gynecological surgery.The search was conducted from inception to July 1,2023,and the AGREE Ⅱ and RIGHT tools were used to analyze the current status and quality of the included guidelines/consensus,as well as to conduct a summary of the recommendations.Results A total of 5 guidelines and 10 consensus statements were included.The publication years were from 2018 to 2023,originating from the United States,China,Canada,and the United Kingdom.In the 6 areas evaluated using AGREEⅡ,clarity(66.06％)scored highest,followed by scope and purpose(56.67％),involvement of stakeholders(42.02％),and editorial independence(37.64％)with scores above 30％.The scores for rigor of development(26.88％)and applicability(4.17％)were relatively low.The same items among different evaluators indicated good consistency.The results of the scores in each area were as follows:A-level 2,B-level 13,and no C-level.Two high-quality guidelines were selected.The average RIGHT reporting rate was 44.38％.Subgroup analysis showed that guidelines were higher than consensus statements in the areas of rigor of development and applicability(P＜0.05),and that using GRADE was higher than not using(P＜0.05).The areas of rigor of development and clarity were higher in foreign guidelines than domestic guidelines(P＜0.05),and using evidence grading tools was higher than not using(P＜0.05).The summary of the recommendations showed that the quality of the evidence supporting the recommendations was uneven,and some recommendations were not specific enough.Conclusion The quality of the 15 included ERAS guidelines/consensus in obstetrics and gynecology is uneven,and 2 of them can be used as high-quality guidelines for clinical reference.The quality of evidence-based guidelines in foreign countries is higher,and the use rate of GRADE in foreign guidelines is high,most of which can provide clear recommendation strength and evidence level.Chinese guidelines/consensus are of lower quality compared to overseas,and methodology and report quality need further improvement.Overall,it is still necessary to strengthen the formulation of methods and reporting standards,improve the quality of evidence,and refine specific recommendations.

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Purpose: Investigation of stroke lesions mostly focuses on the grey matter (GM). White matter (WM) degeneration during acute stroke has remained understudied. In the present study, monkeys were employed to investigate the alterations in GM and WM in the brain following ischemic occlusion using diffusion tensor imaging (DTI). Materials and Methods: Permanent middle cerebral artery occlusion was induced in rhesus monkeys (n = 6) using an interventional approach. Serial DTI was conducted on a clinical 3 T in the hyperacute phase (2–6 hours), 48, and 96 hours post-occlusion. Regions of interest in GM and WM of lesion areas were selected for data analysis. Results: Mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) in WM decreased substantially during hyperacute stroke, similar to those seen in GM. No obvious fractional anisotropy changes were seen in WM during the hyperacute phase until 48 hours poststroke when significant fiber loss was observed. Pseudo-normalization of MD, AD, and RD was seen at 96 hours. Pathological changes in WM and GM were observed in ischemic areas at 8, 48, and 96 hours poststroke. Relative changes in MD, AD, and RD of WM were correlated negatively with infarction volumes at 6 hours poststroke. Conclusion The present study revealed the microstructural changes in GM and WM of monkey brains during acute stroke using DTI. The preliminary results suggest that AD and RD may be sensitive surrogate markers to assess specific microstructural changes in WM during the hyperacute stroke.

Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,

Background/Aims: Disaccharidase assay is used for assessing carbohydrate intolerance in children, but its usefulness in adults is not known. The aim of this study is to assess the prevalence of disaccharidase deficiency in patients with unexplained gastrointestinal symptoms. Methods: A retrospective review of adults with chronic (> 1 year) abdominal symptoms and negative imaging and endoscopy/colonoscopy and who completed bowel symptom questionnaire and duodenal biopsy for lactase, maltase, sucrase, and palatinase was performed. A subset also underwent 25 g lactose breath test (LBT). Results: One hundred twenty patients (females = 83) were evaluated, of whom 48 also underwent LBT. Fifty-six (46.7%) patients had enzyme deficiency; 44 (36.7%) had single (either lactase or maltase), 1 had 3 enzyme deficiencies, 11 (9.2 %) had all 4 disaccharidase enzyme (pan-disaccharidase) deficiency, and 64 (53.0%) had normal enzyme levels. Baseline prevalence and severity of 11 gastrointestinal symptoms were similar between normal and single enzyme deficiency groups. The sensitivity and specificity of LBT was 78.3% and 72.0%, respectively and overall agreement with lactase deficiency was 75.0%. Conclusions Isolated disaccharidase deficiency occurs in adults, usually lactase and rarely maltase, and pan-disaccharidase deficiency is rare. Baseline symptoms or its severity did not predict enzyme deficiency.

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Objective To investigate the stroke classification of different age groups in Ganzi Tibetan Autonomous Prefecture,Sichuan Province in order to provide a basis for targeted prevention and treatment of stroke in the area. Methods From October 2011 to June 2014,a cross-sectional survey was used for cluster sampling and stratified sampling in 10000 residents,farmers,and herdsmen in Dege,Ganzi,Litang, Batang,and Kangding counties,Ganzi Tibetan Autonomous Prefecture,Sichuan Province. The questionnaires were used to collect demographic characteristics,stroke,hypertension,and other information. A total of 9186 effective questionnaire responders were enrolled. According to their ages,they were divided into five groups (18-29,-39,-49,-59,and ≥60 years). The included respondents in each group were 2492,2356, 2161,943,and 1234,respectively. Strokes were classified as transient ischemic attack,cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage groups. The differences in the prevalence among the groups used chi-square test. Results In 9186 subjects, 4584 ( 49. 9%) were females and 4602(50. 1％) were males. There were 174 patients with stroke,the prevalence was 1. 89％. The incidences of stroke in 5 age groups from small to large were 0. 08％％ (2/2492),0. 68％ (16/2356),1. 39％ (30/2161),2. 65％ (25/943),and 8. 18％ (101/1234),respectively. There were significant differences in the incidence of cerebrovascular diseases in different age groups (χ2 =693. 72,P<0. 01). The proportions of cerebral infarction,intracerebral hemorrhage,transient ischemic attack,and subarachnoid hemorrhage in the classification of stroke were 44.2％ (n=77),43.7％ (n=76),7.5％ (n=13),and 4.6％ (n=8),respectively. The prevalence of hypertension in the above stroke types were 77. 9％ (60/77),94. 7％(72/76),7/13 and 5/8,respectively. Conclusions The prevalence of cerebrovascular diseases is high in Ganzi Tibetan Autonomous Prefecture,Sichuan Province,and hemorrhagic stroke is significantly higher, the incidence of hypertension is the highest,which suggests that hypertension is an important risk factor for high incidence of hemorrhagic stroke in the local area. It is necessary to do a good job of health education on stroke according to the characteristics of local stroke