Zhusha Anshenwan is a classical traditional Chinese medicine （TCM） formula originating from LI Dongyuan's Treatise on the Differentiation of Endogenous and Exogenous Injuries （Nei Wai Shang Bian Huo Lun） of the Jin-Yuan period. It is composed of five medicinal ingredients： Cinnabaris （Zhusha）， Coptidis Rhizoma （Huanglian）， Angelicae Sinensis Radix （Danggui）， Rehmanniae Radix （Shengdihuang）， and Glycyrrhizae Radix et Rhizoma （Gancao）. Under the guidance of TCM theory， this formula is used to treat syndromes of disturbed spirit， including insomnia， palpitations， and anxiety， caused by hyperactivity of heart fire and deficiency of Yin-blood， and it also exerts auxiliary anticonvulsant effects in epilepsy and related conditions. However， the potential neurotoxicity， hepatotoxicity， and nephrotoxicity of its monarch drug， Cinnabaris （mainly composed of mercuric sulfide， HgS）， together with the risk of in vivo accumulation， have rendered its clinical application controversial， and it has not yet been formally included in the Pharmacopoeia of the People's Republic of China. In addition， restrictions imposed by the Minamata Convention on Mercury have led to an increasing shortage of natural medicinal Cinnabaris resources， making the evaluation of the efficacy and safety of synthetic Cinnabaris particularly urgent. This contradiction highlights the complexity of safety evaluation for traditional medicines. Existing studies indicate that Zhusha Anshenwan exhibits definite pharmacological activities in calming the mind， improving sleep， and regulating emotional disorders. Moreover， other components of the formula may exert antagonistic effects on the toxicity of Cinnabaris， and reports of severe mercury poisoning caused by standardized clinical use of this prescription are extremely rare. Research suggests that other ingredients in the compound formula， such as Rehmanniae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma， may effectively alleviate the hepatorenal toxicity of Cinnabaris through mechanisms including modulation of the gut microbiota， formation of mercury complexes， and direct protection of target organs. This article aims to systematically review the progress in pharmacodynamic research on Zhusha Anshenwan， to explore its mechanisms of action in depth， and to analyze the toxicokinetic characteristics and safety risks of Cinnabaris， as well as the scientific connotations of toxicity reduction and efficacy enhancement achieved through compound compatibility. In addition， it compares Zhusha Anshenwan with other commonly used sedative formulas， with the aim of providing a scientific basis and forward-looking perspectives for the safe and rational application and in-depth development of this classical prescription in a modern context， and of emphasizing the important value of holistic research on TCM compound formulas in addressing the challenges of single-component toxicity.

Objective:To develop the Adolescent Mental Health Computerized Adaptive Test(AMH-CAT)for assessing psychological crises in adolescents using item response theory(IRT).Methods:A total of 8 679 students,aged 9 to 19 years,were sampled from 14 primary and secondary schools.The item bank was constructed by examining unidimensionality,independence,discrimination,and Differential Item Functioning(DIF).The AMH-CAT algorithm was developed using R software and validated for reliability and validity through real and simulated data.The School Psychological Interview Evaluation Form served as the criterion tool to assess the predictive validi-ty of AMH-CAT in evaluating psychological crises levels.Results:The item bank,consisting of 43 items,demon-strated unidimensionality and independence,with discrimination values＞0.80 and no DIF across genders.Under va-rious stopping rules,AMH-CAT showed ABS values＜0.40,RMSE values＜0.50,and a correlation(r)＞0.87(P＜0.001)between estimated and true psychological crises levels.Real participants answered an average of 10 items under the SE(θ)≤0.4 stopping rule,with a reliability of 0.89,and the scores were positively correlated with the complete item bank scores(r=0.95,P＜0.001).The predictive accuracy for Level 1 and Level 2 concerns was 0.89 and 0.90,respectively.Conclusion:The Adolescent Mental Health Computerized Adaptive Test(AMH-CAT)demonstrates excellent validity,reliability and assessment efficiency for evaluating adolescent psychological crises.

Objective:To analyze the clinicopathological characteristics of atypical teratoid/rhabdoid tumors (AT/RT) and the causes of pathological misdiagnosis, and summarize diagnostic strategies.Methods:A case series study was conducted.Specifically, the data of 5 misdiagnosed(misdiagnosed group) and 8 confirmed AT/RT cases(confirmed group) in the Department of Pathology of Xi′an Children′s Hospital from January 2010 to December 2018 were retrospectively analyzed.Hematoxylin-eosin and immunohistochemical staining were performed to analyze clinical features, morphology, and immune phenotypes.Rates were compared between the misdiagnosed and confirmed groups by a Fisher′s exact test.Means were compared using an independent sample t-test.Medians were compared by a Mann-Whitney U test. Results:(1)There were 4 males and 1 female in the misdiagnosed group, with a median age of 24 months.In this group, 4/5 tumors were located in the posterior cranial fossa, and 1/5 tumors were located in the spinal cord.Morphologically, rhabdoid cells were detected in 3/5 cases, and the other 2/5 cases consisted of small embryonal cells.Immunohistochemically, INI1 and BRG1 expressions were absent in 4/5 and 1/5 cases, respectively.All of them showed multiple immunephenotypes.There were 7 males and 1 female in the confirmed group, with a median age of 22 months.In the confirmed group, 4/8 tumors were located in the supratentorial region and 4/8 tumors were located in the infratentorial region.Rhabdoid cells, deficient INI1 expression and multiple immunephenotypes were observed in all 8 cases.(2)The percentage of rhabdoid cells in the misdiagnosed group was significantly lower[0.45(0, 0.46)] than that in the confirmed group[0.55(0.40, 0.85)]( Z=-2.064, P=0.039). Conclusions:The causes of misdiagnosis of AT/RT are variable sites of occurrence, diverse histomorphology, multiple phenotypes in immunohistochemistry and rare BRG1 deficiency.For high-grade rhabdoid, epithelioid, and/or embryonic small cell tumors, AT/RT should be differentiated and immunohistochemistry protocols should include INI1 and BRG1.

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 establish a detection method for fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.Methods:The detection of fatty acid composition involves pre-test of the sam-ple using the methanol sodium methylation method,followed by direct injection analysis using gas chromatography,and finally calculating the content of each fatty acid composition using the area normalization method with correction factors.The detection of methoxylaniline value is achieved by dissolving and diluting the sample with isooctane:isopropanol(8∶2,volume ratio),reacting with 4-methoxylaniline,measuring the absorbance at a wavelength of 350 nm,and calculating the methoxylaniline value.Results:Under the composition of fatty acids,the 8 kinds of fatty acids have good separation degree.The methyl ricinoleate and methyl stearate have good linear relationship in the range of 0.1-5.0 mg·mL-1.The repeatabilityand intermediate precision(RSD)ofthe determination results of each fatty acid in the sample are all less than 5%.It is also found that only α-type of linolenic acid is present in castor oil,without γ-type.In the determination of methoxyaniline value,the blank solvent does not interfere with the determination of the sample,and the repeatability RSD is 3.6%.Conclusion:The detection method for fatty acid composition and meth-oxylaniline value established in this article is accurate and reliable,and can be used for the detection of fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.

Objective:To analyze the effect of continuous positive airway pressure (CPAP) on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome (OSAS), especially on the incidence of hypertensive disorder in pregnancy (HDP) in women with moderate to severe OSAS.Methods:A total of 180 pregnant women with OSAS who were diagnosed through sleep monitoring during pregnancy due to high-risk factors of OSAS and registered in Peking University People′s Hospital from January 2021 to May 2024 were selected as the study subjects. Clinical data were collected from medical records for retrospective analysis. According to whether they received standardized treatment with CPAP, they were divided into the CPAP treatment group (42 cases) and the control group (138 cases). The CPAP treatment group consisted of 9 pregnant women with moderate to severe OSAS, while the control group consisted of 34 pregnant women with moderate to severe OSAS. The maternal and neonatal outcomes, the incidence of HDP, placental weight after delivery and placental weight/neonatal birth weight ratio were compared between the two groups.Results:(1) The average gestational age of pregnant women in the CPAP treatment group was higher than that in the control group [(38.7±1.0) vs (38.0±1.4) weeks], the proportion of infants small for gestational age (SGA) in the CPAP treatment group was lower [0 (0/42) vs 12.3% (17/138)], and the birth weight of infants in the CPAP treatment group was bigger [(3 396±475) vs (3 082±710) g); the differences between the two groups were statistically significant (all P<0.05). There were no significant differences between the CPAP treatment group and the control group in terms of delivery mode, rates of postpartum hemorrhage and preterm birth, umbilical artery blood gas analysis pH<7.1, lactate≥6.0 mmol/L, base excess<-12.0 mmol/L and the incidence of gestational diabetes mellitus and HDP (all P>0.05). (2) The placental weight of the CPAP treatment group was significantly lower than that of the control group [(554.0±70.6) vs (615.7±119.1) g], the placental weight/newborn birth weight ratio of the CPAP treatment group was significantly lower than that of the control group (median: 0.17 vs 0.19), and the differences were statistically significant (all P<0.05). (3) The incidence of HDP in pregnant women with moderate to severe OSAS in the CPAP treatment group was lower than that in the control group [1/9 vs 61.8% (21/34)], and the difference was statistically significant ( P<0.05). Conclusions:CPAP treatment could prolong the gestational age in pregnant women with OSAS, reduce the incidence of SGA, increase the birth weight of infants, and reduce the incidence of HDP in pregnant women with moderate to severe OSAS, and is worth promoting in clinical practice. The improvement of neonatal outcomes by CPAP treatment is closely related to the placenta, which is worthy of further exploration.

Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.

Objective:To establish a detection method for fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.Methods:The detection of fatty acid composition involves pre-test of the sam-ple using the methanol sodium methylation method,followed by direct injection analysis using gas chromatography,and finally calculating the content of each fatty acid composition using the area normalization method with correction factors.The detection of methoxylaniline value is achieved by dissolving and diluting the sample with isooctane:isopropanol(8∶2,volume ratio),reacting with 4-methoxylaniline,measuring the absorbance at a wavelength of 350 nm,and calculating the methoxylaniline value.Results:Under the composition of fatty acids,the 8 kinds of fatty acids have good separation degree.The methyl ricinoleate and methyl stearate have good linear relationship in the range of 0.1-5.0 mg·mL-1.The repeatabilityand intermediate precision(RSD)ofthe determination results of each fatty acid in the sample are all less than 5%.It is also found that only α-type of linolenic acid is present in castor oil,without γ-type.In the determination of methoxyaniline value,the blank solvent does not interfere with the determination of the sample,and the repeatability RSD is 3.6%.Conclusion:The detection method for fatty acid composition and meth-oxylaniline value established in this article is accurate and reliable,and can be used for the detection of fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.

At present,indocyanine green(ICG)is intraoperative imaging agent with the most of advantages,and the ICG fluorescence imaging technique that derived from it has been widely developed in surgery with laparoscope for colorectal cancer.This technique can effectively realize tumor localization,assessment for resection margin,imaging of lymph node and lymphatic vessel,which has important value in judging the blood supply of the anastomosis,and can further effectively improve surgical safety and reduce the risk of postoperative complications.In addition,ICG fluorescence imaging technique can also powerfully promote the development of minimally invasion and individualization of colorectal surgery.With the advancement of laparoscopic equipment,deepening of medical theory,progress of surgical techniques,and the integration of artificial intelligence and medicine,the application scenarios of ICG imaging technique are gradually expanding.This article reviewed the imaging principles,current status of application,and current existing issues of ICG fluorescence imaging technique in surgery for colorectal cancer,which conducted preliminarily exploration for its value in guiding the practice of the theory of membrane anatomy.

Objective:To analyze the effect of continuous positive airway pressure (CPAP) on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome (OSAS), especially on the incidence of hypertensive disorder in pregnancy (HDP) in women with moderate to severe OSAS.Methods:A total of 180 pregnant women with OSAS who were diagnosed through sleep monitoring during pregnancy due to high-risk factors of OSAS and registered in Peking University People′s Hospital from January 2021 to May 2024 were selected as the study subjects. Clinical data were collected from medical records for retrospective analysis. According to whether they received standardized treatment with CPAP, they were divided into the CPAP treatment group (42 cases) and the control group (138 cases). The CPAP treatment group consisted of 9 pregnant women with moderate to severe OSAS, while the control group consisted of 34 pregnant women with moderate to severe OSAS. The maternal and neonatal outcomes, the incidence of HDP, placental weight after delivery and placental weight/neonatal birth weight ratio were compared between the two groups.Results:(1) The average gestational age of pregnant women in the CPAP treatment group was higher than that in the control group [(38.7±1.0) vs (38.0±1.4) weeks], the proportion of infants small for gestational age (SGA) in the CPAP treatment group was lower [0 (0/42) vs 12.3% (17/138)], and the birth weight of infants in the CPAP treatment group was bigger [(3 396±475) vs (3 082±710) g); the differences between the two groups were statistically significant (all P<0.05). There were no significant differences between the CPAP treatment group and the control group in terms of delivery mode, rates of postpartum hemorrhage and preterm birth, umbilical artery blood gas analysis pH<7.1, lactate≥6.0 mmol/L, base excess<-12.0 mmol/L and the incidence of gestational diabetes mellitus and HDP (all P>0.05). (2) The placental weight of the CPAP treatment group was significantly lower than that of the control group [(554.0±70.6) vs (615.7±119.1) g], the placental weight/newborn birth weight ratio of the CPAP treatment group was significantly lower than that of the control group (median: 0.17 vs 0.19), and the differences were statistically significant (all P<0.05). (3) The incidence of HDP in pregnant women with moderate to severe OSAS in the CPAP treatment group was lower than that in the control group [1/9 vs 61.8% (21/34)], and the difference was statistically significant ( P<0.05). Conclusions:CPAP treatment could prolong the gestational age in pregnant women with OSAS, reduce the incidence of SGA, increase the birth weight of infants, and reduce the incidence of HDP in pregnant women with moderate to severe OSAS, and is worth promoting in clinical practice. The improvement of neonatal outcomes by CPAP treatment is closely related to the placenta, which is worthy of further exploration.