AIM: To evaluate the efficacy and safety of 3% diquafosol sodium eye drops in children wearing orthokeratology lenses and with dry eye disease(DED)or at risk of DED.METHODS: Randomized controlled trials. Children with DED or at risk of DED were randomly assigned in a 1:1 ratio to receive either 3% diquafosol sodium eye drops 6 times daily or a blank control at Chongqing Aier Children's Eye Hospital from November 2023 to November 2024. The primary endpoint was the change in the Dry Eye Questionnaire-5(DEQ-5)score from baseline at 12 wk. Secondary assessments included non-invasive breakup time(NIBUT), tear meniscus height, Schirmer's test, corneal fluorescein staining score, and axial length.RESULTS: A total of 80 participants(80 eyes)were enrolled(40 in each group), the average age of the participants was 11.11±1.88 years, with 43 females(54%)and 37 males(46%), and all completed the trial. After 12 wk, the DEQ-5 scores for the diquafosol sodium group and the blank control group were 1.88±2.02 and 2.88±2.79, respectively(P=0.079). The diquafosol sodium group demonstrated a significant improvement in DEQ-5 dryness symptom scores(-0.33±0.66 vs. 0.05±0.81, P=0.023)and NIBUT(6.18±3.73 vs. -1.09±4.40 s, P<0.001)at 12 wk. Additionally, the diquafosol sodium group showed no axial length elongation, in contrast to the blank control group, which exhibited elongation(0.00±0.08 vs. 0.05±0.10 mm, P=0.013). No other significant differences were found in the secondary endpoints. No adverse events occurred during the trial.CONCLUSION: Although no statistically significant improvements were noted in the overall DEQ-5 scores, the 3% diquafosol sodium eye drops significantly improved dryness symptoms and NIBUT when compared to the blank control group.

Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

ObjectiveTo investigate the impact of anticentromere antibody （ACA） on the clinical features and prognosis of patients with primary biliary cholangitis （PBC） by comparing clinical classification， ursodeoxycholic acid （UDCA） response， GLOBE score， and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients. MethodsA total of 749 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients. According to their conditions on admission， the two groups were compared in terms of the distribution of clinical types， i.e.， chronic progression-type PBC， portal hypertension-type PBC， and standard jaundice/liver failure-type PBC. There were 261 patients with complete data after 1-year follow-up， among whom there were 53 patients with positive ACA and 208 with negative ACA. A statistical analysis was performed， and propensity score matching was performed based on sex and age at a ratio of 1∶2. The two groups were compared in terms of 1-year UDCA response rate， GLOBE score， and UK-PBC score before and after matching. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the ACA-negative group， the ACA-positive group had a significantly higher age （61.28±10.35 years vs 56.74±12.17 years， t=4.164， P<0.001）， a significantly higher proportion of female patients （93.9% vs 77.6%， χ²=20.221， P<0.001）， a significantly higher proportion of patients with portal hypertension （48.3% vs 27.6%， χ²=23.289， P<0.001）， and a significantly lower proportion of patients with jaundice/liver failure （24.5% vs 38.5%， χ²=10.205， P<0.001）. After 1-year follow-up， for the 261 PBC patients with complete data， there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group （41.5% vs 41.8%， P>0.05）， and there was a significant difference in the proportion of patients with a GLOBE score of >0.3 between the ACA-positive group and the ACA-negative group （92.5% vs 80.3%， χ²=3.935， P=0.047）. There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching， and there were no significant differences between the two groups in UDCA response rate， GLOBE score， and UK-PBC score （all P>0.05）. ConclusionACA-positive patients tend to have an older age， with a higher proportion of female patients or patients with portal hypertension， while there is a relatively low proportion of patients with jaundice/liver failure. Positive ACA has no significant impact on UDCA response rate， GLOBE score， and UK-PBC score.

As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

The purpose of this paper is to explore the decoction and dosing methods of rhubarb root and rhizome in classical prescriptions and to provide a reference basis for the clinical use of rhubarb root and rhizome. By collating the relevant classical prescriptions of rhubarb root and rhizome in Shanghan Lun and Jingui Yaolüe, the relationship between its decoction and dosing methods and the syndrome was analyzed. The decoction of rhubarb root and rhizome in classical prescriptions can be divided into three categories: simultaneous decoction, decoction later, and other methods (impregnation in Mafei decoction, decoction with water from the well spring first taken in the morning, and pills). If it enters the blood level or wants to slow down, rhubarb root and rhizome should be decocted at the same time with other drugs. If it enters the qi level and wants to speed up, rhubarb root and rhizome should be decocted later. If it wants to upwardly move, rhubarb root and rhizome should be immersed in Mafei decoction. If it wants to suppress liver yang, rhubarb root and rhizome should be decocted with water from the well spring first taken in the morning. If the disease is prolonged, rhubarb root and rhizome should be taken in pill form. The dosing methods of rhubarb root and rhizome can be divided into five categories: draught, twice, three times, before meals, and unspecified. For acute and serious illnesses with excess of pathogenic qi and adequate vital qi, we choose draught. For gastrointestinal diseases, we choose to take the medicine twice. For achieving a moderate and long-lasting effect, we choose to take the medicine three times. If the disease is located in the lower part of the heart and abdomen, we choose to take it before meals. The use of rhubarb root and rhizome in clinical practice requires the selection of the appropriate decoction and dosing methods according to the location of the disease, the severity of the disease, the patient′s constitution, and the condition after taking the medicine.

ObjectiveTo investigate the effects and potential mechanisms of morning and evening fasting on postprandial lipid responses, a post hoc analysis based on a crossover randomized controlled trial was conducted to assess the effects of different fasting strategies on postprandial lipid metabolism in community residents in Shanghai. MethodsA total of 23 participants took part in a randomized crossover trial involving two intervention days: morning fasting and evening fasting, with a washout period of 6 days between intervention days. Two-way analysis of variance was used to test the differences in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the relative expression of circadian clock genes before and after the next meal under fasting. Wilcoxon rank sum tests were used to analyze the different metabolites between the two groups. Principal component analysis and Orthogonal partial least squares-discriminant analysis were conducted to evaluate the ability of metabolites to differentiate between morning fasting and evening fasting and identify the important differential metabolites. After adjusting for age, sex, and BMI, a partial correlation analysis was performed to identify metabolites associated with plasma lipids. In addition, important metabolites associated with plasma lipids were computed by pathway enrichment analysis. ResultsAfter evening fasting intervention, fasting TG level [(0.37±0.29) vs (0.27±0.18)] mmol·L^-1, fasting and postprandial change values in TC [(2.74±0.47) vs (2.51±0.27)] mmol·L^-1 and LDL-C [(1.32±0.38) vs (0.99±0.27)] mmol·L^-1 were significantly lower than those after morning fasting (P<0.05). While, change values of fasting LDL-C [(0.89±0.37) vs (1.14±0.37)] mmol·L^-1 and TG [(1.14±0.19) vs (1.28±0.17)] mmol·L^-1 were significantly higher than those after morning fasting intervention (P<0.05). After fasting intervention, the relative expression of AMPK, CRY1, CLOCK, MTNR1B, AANAT, and ASMT was correlated with the amount of plasma lipid changes (P<0.05). Specifically, CLOCK and AANAT were upregulated following evening fasting and downregulated after morning fasting. Among the 217 important differential metabolites, 111 were correlated with plasma lipids, and which were primarily enriched in the cysteine and methionine metabolism pathways (P<0.05). ConclusionCompared to morning fasting, evening fasting was more effective in improving postprandial lipid responses, indicating that an evening fasting window during intermittent fasting could be conducive to cardiovascular disease prevention in adults. Meanwhile, it is suggested that morning and evening fasting may affect lipid responses through circadian rhythm oscillations and the cysteine and methionine metabolism pathways.

Chronic fatigue syndrome (CFS) is a common problem in military maritime navigation, which greatly affects the safety of military missions. The use of animal models to carry out research on the mechanism of CFS and treatment measures is a common method. This paper systematically introduced the construction methods of CFS models such as single-factor and multi-factor models, summarized common evaluation indicators of CFS, including behavioral and biochemical indicators, and summed up key characteristics of CFS animal models in military oceanic navigation combined with common causes of CFS in military contexts, such as prolonged continuous work, high-intensity physical activity, sleep deprivation, psychological stress, and extreme environmental conditions. The key characteristics of the animal models included, but not limited to, chronic fatigue, sleep disorders, impaired cognitive function, psychological stress responses, and abnormal biochemical indicators. Furthermore, this article identified future research directions for CFS animal models in military oceanic navigation to enhance the application value of the models and provide robust support for the health protection and disease prevention of military personnel.

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged