Based on the theory of "shaoyang（少阳） resembling the pivot" and collateral diseases， this article proposes that pulmonary fibrosis （PF） can be divided into three stages including wind bi （痹）， constraint bi， and atrophy bi. The core pathogenesis of PF is the obstruction of the pivot and pulmonary collateral obstruction. In terms of treatment， the basic principles are to harmonize and regulate the pivot， and to promote the circulation of the lung collaterals. Depending on the different characteristics of the "essence-attribute-function"， treatment methods such as harmonizing and regulating the pivot， resolving phlegm and removing stasis， supplementing deficiency and harmonizing collaterals are suggested. This approach ensures the regulation of the pivot， smooth circulation of qi and blood， unblocking of the lung collaterals and nourishing the lung body， achieving the goals of balancing the ascending and descending of qi， removing phlegm and stasis， and relieving cough and wheezing.

Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

ObjectiveTo analyze the correlation between the clinical symptoms， signs， syndrome characteristics and laboratory indicators of cough variant asthma （CVA） and deepen the understanding of the treatment of this disease based on the theory of "Fu Feng". MethodsAn observational study was conducted. A total of 207 CVA patients who visited the respiratory department of the Third Affiliated Hospital of Beijing University of Chinese Medicine from September 2022 to November 2023 were included. The information from the four diagnostic methods and the laboratory test results of patients were collected. Factor analysis was conducted on the information obtained through the four diagnostic methods in TCM， and the nature and location of CVA were extracted. Sample cluster analysis （Q clustering） and the K-means method were used for data clustering analysis to determine the syndrome types of CVA and analyze the syndrome characteristics and differences in laboratory indicators among different syndrome types. ResultsThe main symptom of CVA patients was cough， accompanied by symptoms such as itchy throat， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， chest tightness， hoarseness， bitter mouth， poor appetite， and skin itching. Factor analysis showed that the disease was located in the lung， involving the liver， spleen， and kidney. The pathological factors involved Yin deficiency， Yang deficiency， wind factor， dampness factor， Yin factor， and Qi stagnation. Cluster analysis revealed four syndrome types： Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. Fengfu Yinshang syndrome accounted for the highest proportion， followed by Tanyin Zufei syndrome. There were no significant differences in eosinophil count and percentage， fractional nasal nitric oxide （FnNO） level， and pulmonary function indexes among the four syndromes. The levels of serum total IgE and fractional exhaled nitric oxide （FeNO） in patients with Fengfu Yinshang syndrome were significantly higher than those in patients with Shixie Neiyun syndrome and Tanyin Zufeisyndrome. ConclusionCough is the main symptom of CVA， accompanied by pharyngeal itching， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， and allergic manifestations. The disease involves the lung， liver， spleen， and kidneys. The essence of the pathogenesis lies in a latent dormant pathogen and a disorder of the pivot mechanism. The four common syndrome types are Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. The TCM syndrome types are correlated with laboratory indexes. The serum total IgE and FeNO of patients with Fengfu Yinshang syndrome are worse.

ObjectiveTo observe the regulation effect of Sangmei Zhike granules on airway inflammation and cyclic adenosine monophosphate （cAMP）-protein kinase A （PKA）-cAMP response element binding protein （CREB） pathway in cough variant asthma （CVA） rats with Fengfu Yinshang syndrome. MethodsEight-week-old male rats were randomly divided into a blank group， model group， western medicine group， and traditional Chinese medicine （TCM） group. Except for the blank group， Fengfu Yinshang models of CVA were established in the other groups. On the 16th day of the experiment， the western medicine group was treated with budesonide aerosol inhalation （dosage of 0.5 g·L^-1）， and the TCM group was given Sangmei Zhike granules by gavage （dosage of 4.19 g·kg^-1·d^-1）， with each group treated once daily for 14 days. On the 30^th day of the experiment， lung function parameters were determined. Whole blood inflammatory cell detection， hematoxylin-eosin （HE） staining of lung tissue， and immunohistochemistry were used to detect the expression of CREB， phosphorylated CREB （pCREB）， and phosphorylated vasodilator-stimulated phosphoprotein （pVASP） proteins in rat lung tissue， and Reverse transcription quantitative polymerase chain reaction （Real-time PCR） was used to determine the protein expressions of cAMP， CREB， and PKA in rat lung tissue. Western blot （WB） was used to detect the expression of PKA， VASP， p-VASP， CREB， and p-CREB proteins. ResultsCompared with the model group， the average dynamic lung compliance （CDyn_average） in the TCM group increased （P0.05）. Compared with the model group， the TCM group showed a decrease in absolute and percentage values of neutrophils （NEUT%）， absolute values of lymphocytes （LYMPH）， absolute and percentage values of basophils （BASO%）， absolute values of monocytes （MONO）， absolute and percentage values of eosinophils （EOS%）， and white blood cells （WBC） （P0.05）. Compared with the western medicine group， the TCM group showed a decrease in MONO， EOS%， and LYMPH% and an increase in MONO% （P0.05）. ELISA results showed that compared with the model group， the TCM group had increased interferon-gamma （IFN-γ） and decreased interleukins （IL）-4， IL-5， IL-13， and total serum IgE， while the Western medicine group had increased IFN-γ and decreased IL-5， IL-13， and total serum IgE （P0.05）. Compared with the western medicine group， the TCM group had decreased IL-5 （P0.05）. HE staining results of rat lung tissue showed that the ciliated epithelium of the D bronchi in the TCM group recovered well. Mucous edema secretion decreased， and a small number of bronchiolar epithelial cells were shed， with reduced infiltration of inflammatory cells and the degree of epithelial injury. Immunohistochemical （IHC） results showed that compared with the model group， positive expressions of CREB， pCREB， and pVASP （brownish-yellow） were significantly increased in the TCM and western medicine groups. Real-time PCR results showed that compared with the model group， the relative expression levels of cAMP， CREB， and PKA in the TCM group were significantly increased （P0.05）， and compared with the western medicine group， the TCM group also showed significantly increased relative expression levels of cAMP， CREB， and PKA （P0.05）. WB results showed that compared with the model group， the expressions of PKA， VASP， p-VASP， CREB， p-CREB， and p-CREB/CREB proteins were increased in the TCM group， while p-VASP/VASP protein expression decreased （P0.05）. Compared with the western medicine group， the TCM group had increased expressions of PKA， VASP， and p-CREB proteins and decreased p-VASP/VASP expression （P0.05）. ConclusionSangmei Zhike granules have the effect of improving lung function and inhibiting airway inflammation in rats with CVA due to Fengfu Yinshang syndrome， possibly related to the activation of the cAMP/PKA/CREB pathway.

Cough variant asthma （CVA） is a special type of asthma and the most common cause of chronic cough in China. It has a relatively high incidence， seriously affects patients' quality of life， and in some cases may even progress to typical asthma， posing an important challenge in the field of health economics. At present， first-line treatment in Western medicine mainly consists of inhaled corticosteroids combined with bronchodilators. However， there remain many problems such as poor efficacy in some patients， frequent relapse after drug withdrawal， and poor compliance， making it urgent to improve treatment strategies. In-depth research on the pathogenesis is helpful for a comprehensive understanding and prevention of CVA. The pathogenesis of CVA is complex and involves multiple pathophysiological links. While similar to typical asthma， it still presents some differences. Traditional Chinese medicine （TCM） has unique advantages in the treatment of CVA. Guided by the theory of syndrome differentiation and treatment， TCM can not only improve the clinical symptoms of CVA but also prevent recurrence. In recent years， with the continuous deepening of research on the pathogenesis of CVA and on its treatment with TCM based on syndrome differentiation， related academic achievements have been updated year by year. A review of literature in China and abroad shows that the current pathogenesis of CVA can be summarized into six aspects： airway inflammation， airway remodeling， airway hyperresponsiveness， cough hypersensitivity， genetic factors， and imbalance of intestinal flora. TCM often differentiates and treats CVA from four perspectives： cause， disease location， disease nature， and disease tendency. This paper systematically summarizes the progress in the study of CVA pathogenesis， comprehensively collates the experience and clinical research evidence on its treatment with TCM based on syndrome differentiation， and discusses the problems existing in current research. On this basis， it puts forward suggestions and prospects for future research and development of TCM in the treatment of CVA， with a view to providing a theoretical basis and therapeutic approaches for its prevention and treatment.

Objective·To explore the value of combined diaphragm and intercostal muscle ultrasound assessment compared with conventional diaphragm ultrasound in predicting the weaning outcome in mechanically ventilated patients with sepsis.Methods·Mechanically ventilated patients with sepsis,consecutively admitted to the Department of Critical Care Medicine of Affiliated Hospital of Nantong University from October 2022 to December 2023,were selected.During the peri-weaning period,after the patient's sepsis condition improved and the patient passed the spontaneous breathing trial(SBT),ultrasound evaluation of respiratory muscles was performed by ultrasound qualified personnel with ultrasound qualification and experience in bedside ultrasound examination.Diaphragm excursion(DE),thickening fraction of diaphragm(TFD),and thickening fraction of intercostal muscle(TFic)were measured,respectively.The patients were divided into a successful weaning group(n=114)and a failed weaning group(n=24)according to the weaning results.Receiver operating characteristic(ROC)curves were used to analyze the value of diaphragm ultrasound and intercostal muscle ultrasound,alone and in combination,in predicting ventilator weaning outcome.Results·TFic and TFic/TFD were significantly higher in the failed weaning group during SBT than in the successful weaning group(all P<0.05).The areas under the ROC curve(AUROC)of DE,TFD,and TFic to predict weaning failure in mechanically ventilated patients with sepsis during the period of SBT were 0.689(0.591?0.776),0.657(0.557?0.747),and 0.769(0.676?0.846),respectively,whereas the combined indexes TFic/TFD and TFic&TFD_mix had AUROCs of 0.867(0.786?0.925)and 0.860(0.778?0.920),respectively.TFic/TFD with a cutoff value of>0.95 had a sensitivity of 86.7%and a specificity of 75.3%in predicting weaning failure,and TFic&TFD_mix with a cutoff value of>0.13 had a sensitivity of 86.6%and a specificity of 80.9%in predicting weaning failure.Moreover,the intercostal muscle ultrasonography method had an intra-observer intraclass correlation coefficient(ICC)of 0.890 and an extra-observer ICC of 0.876 for measurement reliability,which were both rated as good(P<0.001).Conclusion·Combined diaphragm and intercostal muscle ultrasonography provides a more comprehensive picture of the patient's overall respiratory muscles,and has a higher guiding value in predicting the weaning outcomes in mechanically ventilated patients with sepsis than diaphragm ultrasound alone.

Objective To explore the biomechanical safety of applying traditional Chinese orthopedic manipulation therapy after anterior cervical discectomy and fusion(ACDF)surgery,so as to provide a theoretical basis for clinical treatment in biomechanics.Methods Based on CT data,a three-dimensional finite element model of the normal C0-T1 cervical spine was established,and an ACDF postoperative finite element model of the C5-6 segment was constructed on this basis.Cervical spine rotation manipulation was simulated at the C4 and C7 segments of both models,and the von Mises stresses of the vertebral body,bilateral facet joints,intervertebral discs,and internal fixation system under manipulation loading of the C4 and C7 segments in both models were compared and analyzed.Results When the C4 segment was manipulated,the stress on the C5,C6,and C7 vertebral bodies in the ACDF postoperative model decreased by 12.3％,11.5％,and 26.4％,compared to the normal model.The stress on the left facet joints of the C4-5,C5-6,and C6-7 segments decreased by 12.3％,58.8％,and 15.4％,and the stress on the right facet joints decreased by 16.6％,92.1％,and 17.2％.The stress on the C4-5 and C6-7 segments decreased by 13.2％and 4.0％,while the maximum stress of the fusion cage,titanium plate,and screws in the C5-6 segment were 9.349,111.9,and 300.8 MPa.When the C7 segment was manipulated,the stress on the C4,C5,and C6 vertebral bodies in the ACDF postoperative model increased significantly compared to the normal model,especially the C5 vertebral body,with an increase of nearly 18 times.Except for the stress on the left facet joint of the C4-5 segment increased by 57.7％,the stress on the bilateral facet joints of other segments generally decreased,but the stress on the C4-5 and C6-7 segments increased by 43.2％and 21.7％and the stresses on the fusion cage,titanium plate,and screws in the C5-6 segment were 2.926,205.4,and 256.2 MPa.Conclusions The safety of performing manipulation on the upper vertebral body of the fusion segment after ACDF surgery is relatively high,but performing manipulation on the lower vertebral body of the fusion segment may lead to stress concentration and increase the risk of injury.When postoperative conservative treatment is implemented,the manipulation safety and indications should be considered to avoid operations in high-risk areas,and more precise and safe manipulation intervention treatment should be implemented based on the specific postoperative biomechanical state of the patient.

Objective To explore the biomechanical characteristics of different types of lumbar disc herniation(LDH),and provide a theoretical basis for the clinical classification,diagnosis,and treatment of LDH.Methods A normal lumbar spine model with spinal nerves and four types of LDH models(central type,paracentral type/lateral recess type,intervertebral foramen type,extreme type)were constructed,and the biomechanical characteristics of the intervertebral discs and nerve roots in neutral posture and under six degrees of freedom conditions were analyzed.Results In neutral position,the stress of normal intervertebral disc was carger than that of the herniated intervertebral disc,and the stress ratio of annulus fibrosus and nucleus pulposus in normal model was greater than that of annulus fibrosus and nucleus pulposus in herniated models.In neutral position,the disc stress was mainly concentrated at the incisor between the protrusion and normal part,and recruitment occurred at outer edge of the disc.In flexion and extension position,the stress of the herniated intervertebral disc shifted to the right side.The maximum stress of herniated intervertebral disc appeared during right flexion,and the nerve root stress on the right side was carger than that on the left side.The stress of the herniated intervertebral disc during right rotation was slightly lower than that during right flexion,and the stress of nerve root on the right side was smaller than that on the left side.Conclusions The intervertebral disc is important in maintaining lumbar dynamic and static stability and flexibility.Different positions have an obvious effect the intervertebral disc stress.For patients with LDH,forward bending,flexion of the affected side and large extension should be avoided.Appropriate rotation of the affected side can help relieve the symptoms of nerve root compression.