ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

The excipient processing is an essential part of traditional Chinese medicine processing, and understanding its scientific connotations is a critical scientific issue that urgently needs resolution. Building upon a foundation where the composition of traditional Chinese medicine substances is fundamentally clear, this paper applies the techniques and methods of chemoinformatics to the study of the excipient processing mechanism. Relevant information on traditional Chinese medicines processed with four kinds of excipients (wine, vinegar, salt and honey) was collected, including properties, taste, meridian tropism, chemical components, etc. Molecular descritors and skeletons corresponding to each chemical component were calculated using chemoinformatics to characterize the properties and structural features of the components. Characteristic components associated with the four excipients (wine, vinegar, salt and honey) were explored through multivariate statistical analysis and Murcko skeleton analysis. Further analysis, taking honey-processed Astragali Radix as an example, the focus was on the impact of the processing excipient honey on the solubility and permeability of its characteristic pharmacologically active components (isoflavones). It was discovered that the excipient honey can increase their solubility and permeability, emphasizing that the impact of processing excipients on the pharmacological classification properties is a key breakthrough in elucidating the mechanism of excipient processing. In summary, this study analyzed the characteristic components associated with the processing excipients "wine, vinegar, salt and honey" based on their composition characteristics, providing data support for the research on the mechanism of excipient processing from a biopharmaceutical perspective.

Biomacromolecule drugs have been increasingly used in clinical practice due to their distinct advantages, including precise targeting, small dose, high safety and activity. However, owing to their high molecular weight, strong hydrophilicity, and poor stability in the gastrointestinal tract, the oral bioavailability of the biomacromolecule drugs remains extremely poor. As a novel and innovative technology for active drug delivery, gastrointestinal microneedles hold immense potential in the oral delivery of biomacromolecule drugs because of their low-invasive nature and high permeation enhancement effects. This review primarily summarizes the actuating force, design strategies, fabrication techniques, and applications of gastrointestinal microneedles for the oral delivery of biomacromolecule drugs. Additionally, the challenges and further perspectives in the development this technology are presented, aiming to promote the subsequent research and clinical translation of gastrointestinal microneedles, and to provide a new efficient and safe strategy for oral delivery of biomacromolecule drugs.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO₂) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO₂ was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO₂ for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO₂ as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO₂ and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO₂ concentration was (32.18±10.36) μg/cm³. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T₁ group of NDVI, the risk of hypertension was lower in the T₃ group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T₁ group of NO₂, the risk of hypertension was higher in the T₂ and T₃ groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO₂ was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO₂ had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO₂ are associated with hypertension in older adults.
Aged ; Humans ; Female ; Nitrogen Dioxide ; Air Pollution ; Prevalence ; Hypertension/epidemiology* ; China/epidemiology* ; Particulate Matter/analysis*

Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [β (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (P_interaction=0.022). Compared with the Q₁ group in NDVI, WC of Q₂ and Q₃ groups in rural decreased, and the β (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (P_interaction=0.284). Compared with the Q₁ group in NDVI, the risk of central obesity in the Q₂ and Q₃ groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (P_nonlinear=0.006) and central obesity (P_nonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.