ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription （SQWF） on chronic obstructive pulmonary disease （COPD）. MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide （LPS） combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group， a model group， low-， medium-， and high-dose SQWF groups （2.835， 5.67， 11.34 g·kg^-1）， and a Yupingfeng group （1.35 g·kg^-1）. Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed， and the lung function in each group was assessed. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid （BALF） was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. The release level of lactate dehydrogenase （LDH） in BALF was detected by a microplate assay. Reactive oxygen species （ROS） levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde （MDA）， total superoxide dismutase （SOD）， and reduced glutathione （GSH） in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein （TXNIP） and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， Caspase-1 p20， gasdermin D （GSDMD）， GSDMD N-terminal active fragment （GSDMD-N）， interleukin-1β （IL-1β）， and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group， the model group showed lassitude， fatigue， tachypnea， and audible phlegm sounds， and lung function significantly declined （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly （P0.05）. The number of TUNEL-positive cells increased （P0.01）. Levels of LDH， ROS， and MDA in BALF increased significantly （P0.01）， while GSH and SOD activities decreased significantly （P0.01）. Lung tissue cells showed irregular morphology， swollen mitochondria， disrupted cell membranes， and abundant vesicles， i.e.， pyroptotic bodies. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue were significantly elevated （P0.01）， and serum IL-1β and IL-18 levels also increased significantly （P0.01）. Compared with the model group， each medication group showed alleviation of qi deficiency symptoms and improved lung function （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased （P0.05）. The number of TUNEL-positive cells decreased significantly （P0.01）. Levels of LDH， ROS， and MDA decreased significantly （P0.05）， while GSH and SOD activities significantly increased （P0.01）. Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue significantly decreased （P0.01）， and serum IL-1β and IL-18 levels also decreased significantly （P0.05）. ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.

ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription （SQWF） on chronic obstructive pulmonary disease （COPD）. MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide （LPS） combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group， a model group， low-， medium-， and high-dose SQWF groups （2.835， 5.67， 11.34 g·kg^-1）， and a Yupingfeng group （1.35 g·kg^-1）. Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed， and the lung function in each group was assessed. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid （BALF） was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. The release level of lactate dehydrogenase （LDH） in BALF was detected by a microplate assay. Reactive oxygen species （ROS） levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde （MDA）， total superoxide dismutase （SOD）， and reduced glutathione （GSH） in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein （TXNIP） and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， Caspase-1 p20， gasdermin D （GSDMD）， GSDMD N-terminal active fragment （GSDMD-N）， interleukin-1β （IL-1β）， and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group， the model group showed lassitude， fatigue， tachypnea， and audible phlegm sounds， and lung function significantly declined （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly （P0.05）. The number of TUNEL-positive cells increased （P0.01）. Levels of LDH， ROS， and MDA in BALF increased significantly （P0.01）， while GSH and SOD activities decreased significantly （P0.01）. Lung tissue cells showed irregular morphology， swollen mitochondria， disrupted cell membranes， and abundant vesicles， i.e.， pyroptotic bodies. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue were significantly elevated （P0.01）， and serum IL-1β and IL-18 levels also increased significantly （P0.01）. Compared with the model group， each medication group showed alleviation of qi deficiency symptoms and improved lung function （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased （P0.05）. The number of TUNEL-positive cells decreased significantly （P0.01）. Levels of LDH， ROS， and MDA decreased significantly （P0.05）， while GSH and SOD activities significantly increased （P0.01）. Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue significantly decreased （P0.01）， and serum IL-1β and IL-18 levels also decreased significantly （P0.05）. ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

ObjectiveBased on analytic hierarchy process（AHP）-criteria importance through intercriteria correlation（CRITIC） hybrid weighting method， grey relational analysis and backpropagation artificial neural network（BP-ANN）， to optimize the water extraction process of Qizhi prescription， so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL₉（3⁴） orthogonal test was employed， and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components， including astragaloside Ⅳ， polygalaxanthone Ⅲ， calycosin-7-O-β-D-glucoside， tenuifolin， and 3，6′-disinapoylsucrose， as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times， extraction time， and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis， variance analysis， and grey relational analysis. Meanwhile， a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription， and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components（astragaloside Ⅳ， tenuifolin， calycosin-7-O-β-D-glucoside， polygalaxanthone Ⅲ， and 3，6′-disinapoylsucrose） and dry extract yield were 25.7%， 20.82%， 16.41%， 12.45%， 15.96% and 8.67%， respectively. The optimized extraction process parameters were extracted 3 times with 8， 6， 6 times the amount of water， each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results， and the mean square error（MSE） of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible， which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix， and the average comprehensive score of the validation test was 90.85 with the relative standard deviation（RSD） of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules， and the optimized extraction process can effectively improve the extraction efficiency of active ingredients， which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.

Abstract The issue of multimorbidity in children and adolescents is becoming increasingly prominent, but there is no consensus on the definition of multimorbidity. As research deepens, issues related to the comparability and standardization of relevant findings are gradually emerging. As a solution, a systematic review of both domestic and international research on multimorbidity is conducted, and a classification system for defining the concept of multimorbidity is proposed, offering more convenient conditions for the advancement of future research and cross study exchange.

OBJECTIVE To provide reference for improving the pre-prescription review system and reducing the occurrence of medication error by analyzing the drug-related problems （DRPs） in the pre-prescription review orders of pediatric outpatient clinics using the Pharmaceutical Care Network Europe （PCNE） classification system. METHODS The data of pre-prescription review orders were retrospectively collected from outpatient department of Shanghai Children’s Medical Center， Shanghai Jiao Tong University School of Medicine from July 2022 to June 2023； DRPs in the pre-prescription review orders were classified and summarized by using the PCNE classification system （version 9.1）， and then analyzed in terms of types and causes of issues， and the acceptance of interventions. RESULTS A total of 66 017 DRPs orders were included， involving 41 165 patients. The proportion of DRPs orders in children aged ≤5 years old was the highest （58.25%）， followed by children aged 6-12 years old （33.52%）； the department with the highest proportion of DRPs was internal medicine of pediatrics department （71.41%）； the department with the highest incidence of DRPs was thoracic surgery department （9.73%）； top three drug categories of DRPs orders were systemic anti- infective drugs （25.26%）， Chinese patent medicines （24.74%） and respiratory drugs （22.38%）. Referring to PCNE classification system， the types of DRPs mainly focused on treatment safety （64.86%）； the reasons of DRPs orders mainly focused on dose selection （82.09%）， of which 41.26% were due to excessive drug dosage； 92.13% of interventions could be accepted and fully executed by doctors. CONCLUSIONS DRPs orders identified by the pre-prescription review system can be effectively analyzed by using PCNE classification system. Pharmacists should focus on medication use in children aged ≤5 years old， update and develop personalized prescription review rules timely， and meet the rational needs of clinical medication for children.

Background/Aims: The association between caffeine intake and constipation remains inconclusive. This study aims to investigate whether caffeine intake is associated with constipation. Methods: This cross-sectional study included 13 941 adults from the 2005-2010 National Health and Nutrition Examination Survey. The weighted logistic regression analyses were exerted to evaluate the association between caffeine intake and constipation. Besides, stratified analyses and interaction tests were conducted to determine the potential modifying factors. Results: After adjusting for confounders, increased caffeine intake by 100 mg was not associated with constipation, as defined by stool frequency (OR, 1.01; 95% CI, 0.94-1.10) or stool consistency (OR, 1.01; 95% CI, 0.98-1.05). Subgroup analyses showed that cholesterol intake modified the relationship between increased caffeine by 100 mg and stool frequency-defined constipation (P for interaction = 0.037). Each 100 mg increase in caffeine intake was associated with a 20% decreased risk of constipation defined by stool frequency in participants who consumed high cholesterol (OR, 0.80; 95% CI, 0.64-1.00), but no association in the other 2 cholesterol level groups. Furthermore, the association between caffeine intake and stool consistency-defined constipation was not found in different cholesterol groups. Conclusions Caffeine consumption is not associated with stool frequency or consistency-defined constipation. Nevertheless, increased caffeine intake may decrease the risk of constipation (defined by stool frequency) among participants in the high-cholesterol intake group.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Objective: To conduct a scoping review on the types, construction methods and predictive performance of health literacy prediction models based on machine learning methods, so as to provide the reference for the improvement and application of such models. Methods: Publications on health literacy prediction models conducted using machine learning methods were retrieved from CNKI, Wanfang Data, VIP, PubMed and Web of Science from inception to May 1, 2024. The quality of literature was assessed using the Prediction Model Risk of Bias ASsessment Tool. Basic characteristics, modeling methods, data sources, missing value handling, predictors and predictive performance were reviewed. Results: A total of 524 publications were retrieved, and 22 publications between 2007 and 2024 were finally enrolled. Totally 48 health literacy prediction models were involved, and 25 had a high risk of bias (52.08%), with major issues focusing on missing value handling, predictor selection and model evaluation methods. Modeling methods included regression models, tree-based machine learning methods, support vector machines and neural network models. Predictors primarily encompassed factors at four aspects: individual, interpersonal, organizational and society/policy aspects, with age, educational level, economic status, health status and internet use appearing frequently. Internal validation was conducted in 14 publications, and external validation was conducted in 4 publications. Forty-two models reported the areas under the receiver operating characteristic curve, which ranged from 0.52 to 0.983, indicating good discrimination. Conclusion Health literacy prediction models based on machine learning methods perform well, but have deficiencies in risk of bias, data processing and validation.