ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework.

ObjectiveTo investigate the effects of Maimendong Yinzi （MMDYZ） on cough with Yin deficiency and lung heat syndrome and explore its potential mechanism of action. MethodsForty-eight Institute of Cancer Research （ICR） mice were randomly divided into a control group， a model group， a Baihe Gujin Tablet （BHGJP） group （1.36 g·kg^-1）， and low-dose， medium-dose， and high-dose MMDYZ groups （5， 10， 20 g·kg^-1·d^-1， based on the weight of crude drug）， with eight mice in each group. The mouse model of cough with Yin deficiency and lung heat syndrome was prepared by a combination of smoke exposure， nasal drip of lipopolysaccharide （LPS）， intragastric gavage with thyroxine， and capsaicin atomization. After successful modeling， drug interventions were administered for seven days. During modeling， the mice were observed for changes in general status， anal temperature， fecal water content， and water intake. After medication， the above indicators were evaluated again， along with assessments of spontaneous activity， cough sensitivity， lung function， lung index， and tracheal phenol red secretion. Bronchoalveolar lavage fluid （BALF） was analyzed for cell differential counts， and the level of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in serum was measured via enzyme linked immunosorbent assay （ELISA）. Lung injury was assessed via hematoxylin-eosin （HE） staining. Network pharmacology was employed to predict the potential mechanism of MMDYZ in alleviation cough with Yin deficiency and lung heat syndrome. Western blot （WB） was used to measure protease-activated receptor1 （PAR1） and GTPhase α_i subunit （Gα_i） protein expressions in lung tissue. ELISA was used to determine lung cAMP content， and immunohistochemistry （IHC） was employed to evaluate transient receptor potential vanilloid subtype 1 （TRPV1） expression. ResultsCompared with the control group， the model group exhibited significantly increased water intake and anal temperature and significantly decreased fecal water content （P<0.05）. The total distance traveled in 5 min and the central zone duration were reduced， while standing frequency significantly increased （P<0.05）. Cough sensitivity and enhanced pause （PenH） were elevated. Peak expiratory flow （PEF） significantly declined （P<0.05）. BALF neutrophil （NEU） and white blood cell （WBC） counts rose. Serum cAMP and cAMP/cGMP ratio significantly increased， and cGMP significantly decreased （P<0.05）. Serum TNF-α and IL-6 levels were significantly elevated （P<0.05）. The lung injury was obvious， and the lung index was significantly elevated （P<0.05）. Compared with the model group， the medium-dose and high-dose MMDYZ groups and the BHGJP group showed significantly improved indicators mentioned above. Additionally， network pharmacology suggested that MMDYZ might alleviate cough with Yin deficiency and lung heat syndrome via cAMP， hypoxia inducible factor-1 （HIF-1）， and TNF signaling pathways. WB， ELISA， and IHC revealed that， compared with the control group， the model group exhibited significantly upregulated PAR1， Gα_i， and TRPV1 expressions and significantly downregulated cAMP in lung tissue （P<0.05）. Compared with the model group， MMDYZ reduced PAR1 （P<0.01）， Gα_i （P<0.05）， and TRPV1 （P<0.01） while increasing cAMP level （P<0.01）. ConclusionMMDYZ may alleviate cough with Yin deficiency and lung heat syndrome by modulating the PAR1/Gα_i/cAMP pathway and TRPV1 expression.

To evaluate the application value of the Peyton four-step teaching method in the standardized training of intestinal ultrasound and compare it with traditional teaching methods, so as to provide an optimized approach for clinical ultrasound training.

ObjectiveTo compare the clinical efficacy of traditional Chinese medicine （TCM） manipulative reduction combined with small splint fixation versus surgical treatment for type A distal radius fracture （DRF） and to explore the factors influencing the choice of treatment. MethodsA multi-center retrospective study was conducted， collecting data from 1237 type A DRF patients treated in 11 hospitals in Jiangsu province from September， 2023 to April， 2025. Among them， 851 patients in the TCM group received manipulative reduction combined with small splint fixation， and 386 patients in the surgical group underwent open reduction and internal fixation. Visual analog scale （VAS） scores for pain and radiographic indicators including palmar tilt， ulnar deviation， and radial height were compared before treatment， 5-7 days after treatment， and 4-6 weeks after treatment. The wrist joint function scores including Dienst and Gartland-Werley scores at 12 weeks after treatment were recorded. Subgroup analysis was conducted for the excellent rate of Dienst and Gartland-Werley scores， stratified by age （＜50， 50-59， 60-69， ≥70 years old） and AO subtypes （A1， A2， A3）. A multivariate logistic regression model was used to identify independent factors influencing treatment choice. ResultsOn 5-7 days after treatment， the surgical group had lower VAS scores than the TCM group， while 4-6 weeks after treatment， the TCM group showed lower VAS scores than the surgical group （P＜0.01）. In terms of radiographic indicators， except for the palmar tilt before treatment being higher in the surgical group than in the TCM group （P＜0.01）， there were no significant differences in palmar tilt， ulnar deviation， and radial height at other timepoints （P＞0.05）. Twelve weeks after treatment， the surgical group had a higher average Gartland-Werley score and the excellent rate than the TCM group （P＜0.01）. Subgroup analysis showed that in patients with A2 type DRF aged 50-59 and 60-69 years old， the excellent rates of Dienst and Gartland-Werley scores in the TCM group were higher than those in the surgical group （P＜0.05）. Multivariate logistic regression analysis revealed that age， palmar tilt， ulnar deviation， and the degree of swelling on the affected side were independent factors influencing the choice of treatment （P＜0.05）. ConclusionBoth TCM manipulative reduction combined with small splint fixation and surgical treatment for type A DRF can achieve good therapeutic effects. TCM manipulative reduction combined with small splint fixation has certain advantages in medium- and long-term pain relief， especially in elderly patients， where wrist joint function recovery is more stable. Age， palmar tilt， ulnar deviation， and swelling degree are the main factors influencing the treatment choice.

Polycystic ovarian syndrome （PCOS） is a common endocrine and metabolic disease mainly occurring among women of childbearing age. Its main symptoms include menstrual disorders， acne， hirsutism， infertility， oily skin， acanthosis nigricans， and obesity. Currently， the etiology and pathogenesis of PCOS remain unclear. Classical formulas， which have rigorous compatibility， concise composition， precise alignment with syndromes， and definitive therapeutic effects， demonstrate unique practical and scientific value in the treatment of PCOS. These formulas exhibit significant clinical efficacy， mild adverse effects， and sustained therapeutic outcomes. To explore the current status and mechanisms of classical formulas in treating PCOS， on the basis of Zhang Zhongjing's academic thoughts on gynecological diseases， this paper reviewed the relevant literature on the treatment of PCOS with classical formulas in recent years. The findings reveal that the pathogenesis of PCOS predominantly involves a combination of internal deficiency and superficial excess， closely related to dysfunction of the liver， spleen， and kidney. The root cause lies in deficiency， and on this basis， there are also symptoms of qi stagnation， blood stasis， phlegm obstruction， and dampness encumbrance. Commonly used classical formulas for treating this disease include Guizhi Fuling pills， Danggui Shaoyao powder， Wenjing decoction， and Jingui Shenqi pills. These classical formulas have good clinical efficacy in treating PCOS. Their mechanisms of action may be related to improving serum levels of sex hormones， increasing the dominant follicle diameter and endometrial thickness， alleviating insulin resistance， lowering glucose and lipid metabolism， inhibiting oxidative and inflammatory reactions in the ovarian tissue， regulating the intestinal flora， correcting the flora disorder， protecting the intestinal barrier function， and regulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. The above research results can help doctors use classical formulas flexibly， broaden diagnostic and therapeutic approaches for PCOS and provide ideas for improving the traditional Chinese medicine diagnosis and treatment plan for PCOS.

Polycystic ovarian syndrome （PCOS） is a common endocrine and metabolic disease mainly occurring among women of childbearing age. Its main symptoms include menstrual disorders， acne， hirsutism， infertility， oily skin， acanthosis nigricans， and obesity. Currently， the etiology and pathogenesis of PCOS remain unclear. Classical formulas， which have rigorous compatibility， concise composition， precise alignment with syndromes， and definitive therapeutic effects， demonstrate unique practical and scientific value in the treatment of PCOS. These formulas exhibit significant clinical efficacy， mild adverse effects， and sustained therapeutic outcomes. To explore the current status and mechanisms of classical formulas in treating PCOS， on the basis of Zhang Zhongjing's academic thoughts on gynecological diseases， this paper reviewed the relevant literature on the treatment of PCOS with classical formulas in recent years. The findings reveal that the pathogenesis of PCOS predominantly involves a combination of internal deficiency and superficial excess， closely related to dysfunction of the liver， spleen， and kidney. The root cause lies in deficiency， and on this basis， there are also symptoms of qi stagnation， blood stasis， phlegm obstruction， and dampness encumbrance. Commonly used classical formulas for treating this disease include Guizhi Fuling pills， Danggui Shaoyao powder， Wenjing decoction， and Jingui Shenqi pills. These classical formulas have good clinical efficacy in treating PCOS. Their mechanisms of action may be related to improving serum levels of sex hormones， increasing the dominant follicle diameter and endometrial thickness， alleviating insulin resistance， lowering glucose and lipid metabolism， inhibiting oxidative and inflammatory reactions in the ovarian tissue， regulating the intestinal flora， correcting the flora disorder， protecting the intestinal barrier function， and regulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. The above research results can help doctors use classical formulas flexibly， broaden diagnostic and therapeutic approaches for PCOS and provide ideas for improving the traditional Chinese medicine diagnosis and treatment plan for PCOS.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

Objective To explore methods for point estimation in adaptive enrichment design,providing a reference for effect estimation inn this context.Methods We simulated efficacy data under adaptive enrichment design and subsequentially estimated the effects using five methods:maximum likelihood method,stage 2 method,Lindley's method,parametric Bootstrap method,and the uniformly minimum variance conditionally unbiased estimated(UMVCUE)method.The performance of these methods was further evaluated.Results The simulation study showed that the maximum likelihood method has a large bias and is very sensitive to some parameters,while Lindley's method tends to underestimate and the parametric bootstrap method sometimes overestimates.The stage 2 method and UMVCUE are almost unbiased.In terms of mean squared error(MSE),all methods perform well except stage 2 estimator.Conclusion In adaptive enrichment design,the UMVCUE performs well in terms of bias and MSE.Therefore,we recommend it as the point estimator for the treatment effect in adaptive enrichment design.

Objective:To study the morphological characteristics and ethnic differences of the chin soft and hard tissue of Han and Uyghur adult females of class Ⅱ 1.Methods:90 Uyghur and Han female subjects of class Ⅱ 1 aged 18-35 years old were enrolled and respectively divided into 3 groups according to the vertical skeletal types:high,average and low angle groups(n=30).The various indexes of the chin soft and hard tissue of the subjects were measured by X-ray lateral cephalic radiographs.The data were statisti-caly analyzed.Results:(1)The Po-Pos of the Han subjects with high angle was higher than that of those with low and average an-gle;the minimum chin thickness,the ratio of the chin thickness to the chin height,the ratio of the minimum chin thickness to the chin thickness and the angle of chin in the high angle group were smaller than those in the average angle group and the low angle group(P＜0.05).The chin height,the chin depression and the cervical-mandibular angle of the Uyghur subjects with high angle were higher than those of the Uyghur subjects with low angle and average angle;the minimum chin thickness,the ratio of the chin thickness to the chin height and the ratio of the minimum chin thickness to the chin thickness in the high angle group were smaller than those in the average and the low angle groups(P＜0.05).(2)In the low angle group,there were significant differences in the angle of chin,cervical-mandibular angle,soft tissue chin angle and Me-Mes between the 2 ethnic groups(P＜0.05).In the average angle group,there were significant differences in the height of chin,LI-LL and Me-Mes between the 2 ethnic groups(P＜0.05).In the high angle group,there were significant differences in the ratio of anterior to posterior chin thickness,in the angle of chin,LL-Pos and Po-Pos between the 2 ethnic groups(P＜0.05).(3)The positive correlation between FH/MP and Po-Pos,cervical-mandib-ular angle,chin depression,chin lip angle,chin height,ratio of anterior and posterior chin thickness and LL-Pos were found in Han and Uyghur subjects(P＜0.05).Mentolabial sulcus,the chin thickness,the ratio of the chin thickness to the chin height,the angle of chin and the ratio of the minimum chin thickness to the chin thickness were negatively correlated with FH/MP in both ethnic groups(P＜0.05).Conclusion:Han and Uy-ghur adult females of class Ⅱ 1 have different chin soft and hard tissue morphology in different vertical skeletal types with certain differences between the ethnic groups in the same vertical skeletal types,and there is a correlation between the chin soft and hard tis-sue morphology of different vertical skeletal types and the vertical skeletal types in Han and Uyghur adult females of class Ⅱ 1.