ObjectiveThis study aims to develop and validate a novel multimodal predictive model， termed criss-cross network（CCNet）-directed graph neural network（DGNN）（CGN）， for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer， by integrating longitudinal chest computed tomography（CT） imaging with both traditional Chinese and western clinical evaluation data. MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron， and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently， a DGNN was constructed to integrate heterogeneous features， where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally， model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss， facilitating robust classification of nodule progression status. ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set， achieving an area under the receiver operating characteristic curve（AUC） of 0.830， accuracy of 0.843， sensitivity of 0.657， specificity of 0.712， Cohen's Kappa of 0.417， and F₁ score of 0.544. Compared with unimodal baselines， the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components， substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine （TCM）-specific symptomatology led to an additional 5% improvement in AUC， underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis， it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features. ConclusionThe CGN model， by synergistically combining cross-attention encoding with directed graph-based feature integration， enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment， thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

ObjectiveTo investigate the identification of kidney Yang deficiency syndrome of patients with osteoporosis（OP）， and to form the clinical syndrome identification rules of traditional Chinese medicine（TCM）. MethodBasic information， etiology， clinical symptoms and other characteristics of 982 OP patients were included， and statistical tests were used to screen the variables associated with kidney Yang deficiency syndrome. Taking the decision tree as the base model， bootstrap aggregation algorithm（Bagging algorithm） was utilized to establish the classification model of kidney Yang deficiency syndrome in OP， generating numerous rules and removing redundancy. Combining least absolute shrinkage and selection operator（LASSO） regression to screen key rules and integrate them to construct an identification model， achieving the identification of kidney Yang deficiency syndrome in OP patients. ResultEighteen key identification rules were screened out， and of these， where 11 rules with regression coefficients>0 correlated positively with the kidney Yang deficiency syndrome， the rule with the highest coefficient was chilliness（present）&feverish sensation over the palm and sole（absent）. The other 7 rules with regression coefficients<0 correlated negatively with the syndrome， the rule with the lowest coefficient was reddish tongue（present）&diarrhea（absent）&deficiency of endowment（absent）. According to the regression coefficients of each key rule， variables with importance>0.2 were ranked as chilliness， reddish tongue， feverish sensation over the palm and sole， cold limbs， clear urine， diarrhea， deficiency of endowment， prolonged illness. The results of the partial dependence analysis of the identification model showed that compared to OP patients without chilliness， those with chilliness（present） had a 0.266 8 higher probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identification of the syndrome. Similarly， compared to OP patients without reddish tongue， those with reddish tongue had a 0.141 9 lower probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identifying non-kidney Yang deficiency syndrome. The accuracy， sensitivity， specificity and area under receiver operating characteristic curve（AUC） of the established kidney Yang deficiency syndrome identification model in the test set were 0.865 9， 0.853 7， 0.872 0 and 0.931 5， respectively. ConclusionA precise identification model of OP kidney Yang deficiency syndrome is conducted basing on the rule ensemble method of Bagging combining LASSO regression， and the screened key rules can explain the identification process of kidney Yang deficiency syndrome. In this research， according to the regression coefficients of rules， the importance and partial dependence of variables， combined with the thinking of TCM， the influence of patient characteristics on the identification of syndromes is described， so as to reveal the primary and secondary syndromes of identification and assist the clinical identification of kidney Yang deficiency syndrome.

ObjectiveTo construct a quantitative differentiation model of traditional Chinese medicine （TCM） syndromes by taking primary osteoporosis （POP） with kidney yang deficiency syndrome as an example， and to provide methodological reference for the standardization of syndrome differentiation. MethodsHigh-frequency clinical features of POP were screened by descriptive statistical analysis， and strong association features of POP were obtained by association rule algorithm. On this basis， a latent structure （latent tree） model was established through latent structure analysis， and the implicit and explicit variables （features） related to POP with kidney yang deficiency syndrome were comprehensively clustered， and the clustering results were interpreted by the indexes of mutual information and cumulative information coverage， to explore the primary and secondary symptoms， and to deduce the categories of POP with kidney yang deficiency syndrome based on the probability of the features appearing in the various latent categories. Based on the categories， the clinical feature scores and identification thresholds were calculated， and the syndrome differentiation model of POP with kidney yang deficiency was initially constructed by combining the comprehensive judgment rules. Finally， the results of TCM professionals' judgment were used as the gold standard to further evaluate the effectiveness of the model in assisting the syndrome differentiation. ResultsThe 32 features strongly associated with POP were obtained， and the Bayes information critedon score of the further constructed latent tree model was -15291.93. Based on the mutual information and the cumulative information coverage， the main symptoms of POP with kidney yang deficiency syndrome were bone weakness， fatigue， pale tongue， clear urine， frequent nocturnal urination， cold limbs， thin pulse， white coating， and secondary symptoms were weakness， loss of libido， loose stool， frequent urination， lumbar and knee weakness， and fear of cold. From the probability of the occurrence of each clinical feature in different latent categories of POP with kidney yang deficiency syndrome， the state was introduced as S0 category （none/mild kidney yang syndrome）/ S1 category （moderate kidney yang syndrome）/ S2 category （severe kidney yang syndrome）. Optimizing the preliminary rules of state identification and refining the state of S1 category， the results showed that among 970 patients with POP， there were 520 patients having no/mild kidney yang deficiency syndrome， 224 patients with moderate to mild kidney yang deficiency syndrome， 81 patients with moderate to severe kidney yang deficiency syndrome， and 145 patients with severe kidney yang deficiency syndrome. During the evaluation and validation process， the correct rate of the model assessment index was 0.8835， while the sensitivity was 0.7181， and the specificity was 0.9437. ConclusionCombined with the latent structure analysis of the association rule， the syndrome differentiation model for POP with kidney yang deficiency could be constructed， and the model shows a good quantitative identification effect， which can provide methodological supports for clinicians to improve the efficiency and accuracy of TCM diagnosis.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Background::Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear.Methods::Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells. Blue-native polyacrylamide gel electrophoresis (PAGE) and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system (MICOS). Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10. Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were used to examine the influence of CHCHD2 in vivo.Results::We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model. Furthermore, we identified that CHCHD2 interacted with Mic10, and overexpression of CHCHD2 can protect against MPP +-induced MICOS impairment, while knockdown of CHCHD2 impaired the stability of MICOS. Conclusion::This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex, which contributes to protecting mitochondrial function in PD.

Objective:To investigate the clinical manifestations and characteristics of tracheobronchial foreign bodies in children, and improve the diagnosis and treatment of foreign bodies.Methods:A retrospective analysis was performed on the clinical data of children with tracheobronchial foreign bodies confirmed by fiberoptic bronchoscopy between January 2010 to December 2019.The children with tracheobronchial foreign body who were treated in the Maternal and Child Health Hospital of Gansu Province.Results:A total of 967 cases were operated by soft electronic bronchoscope, and foreign bodies were removed by means of foreign body forceps or nets.Among them, 19 cases(3 cases with subglottic foreign bodies, one with row of pins, and the rest 15 cases with foreign bodies completely wrapped by granulation)were not removed, two cases were spontaneously coughed, and 946 cases (97.8%)were removed.Bronchial foreign bodies in children were more common in boys, with the ratio of male to female being 2.14∶1.The main age of onset was 1-3 years old(88.8%). The incidence was slightly higher in rural areas than that in urban areas(46.5% in urban areas, 53.5% in rural areas). Foreign bodies were inhaled most in March and least in June.From the perspective of season, winter and spring were more than summer and autumn.The foreign body types inhaled were mainly exogenous plant foreign body, accounting for 93.0%, among which peanut(31.7%)and melon seeds(19.2%)were the most common.The duration of foreign body inhalation was up to 347 cases(35.9%)in 1-3 days.There were 501 cases(51.8%)with endoscopic endobronchial inflammation, and 196 cases of children with varying degrees of granulomatous hyperplasia, accounting for 39.1% and 20.3% of the total.The foreign body in the right bronchus accounted for 50.0% and the left bronchus for 43.7%.There were 793 cases confirmed by imaging, with a positive rate of 81.9%, and 90.9% confirmed by CT.Conclusion:About 88.8% of tracheobronchial foreign bodies occurred in 1 to 3 years of age.The occurrence of foreign bodies had obvious gender, urban-rural and seasonal distribution characteristics, and more cases were male, in rural and winter as well as spring.

Background:China's accelerating development and increasingly important role in global health engagement create a great demand for global health professionals including international consulting experts.This study reported the detailed development and evaluation of an international consulting training for global health workforce.Methods:Based on Kirkpatrick's model,a mixed-methods approach was used to evaluate the effectiveness of the training.Quantitative and qualitative data on participants' reaction,learning,and application of the learned knowledge and skills were collected by a training evaluation survey at the ending of training and a follow-up interview in three months after the training.Results:Thirty-six participants attended the training and 34 of them completed quantitative investigation.The training satisfaction evaluations were positive,for which participants rated the training program highly and over 90％ of them agreed with the usefulness of the training.About knowledge and skills change,participants showed improved consulting knowledge and skills from pre-to post-training (P ＜ 0.001).A total of 23 participants accepted follow-up interview,and most participants applied knowledge and skills learned from the training in their daily work or study.However,only 30.4％ of participants applied their learning in the consulting program.The largest barrier of application was the lack of consulting opportunities.In addition,almost all the participants reported that they would be glad to attend more training courses in the future.Conclusion:The international consulting training program was well-received,and was feasible to improve the consulting service competence of global health professionals.According to participants' feedback,it is essential to develop and expand consulting training in the field of global health.

Objective To explore the management strategy and indications for revisionary internal fixation after percutaneous kyphoplasty/percutaneous vertebroplasty (PKP/PVP) in cancellous vertebral fractures.Methods A retrospective analysis was made of the 676 cases of single-segment PKP/PVP at Department of Orthopaedics,The Affiliated Hospital to Qingdao University from January 2008 to January 2019.They were subjected to 4 different managements after their primary PKP/PVP:rehabilitation without any treatment in 637 cases,conservative treatment in 19 cases (including 3 ones who refused any revision),KP/VP revision in 12 cases and internal fixation revision in 8 cases.The rate of volume reduction after bone cement dispersion (Vx) was calculated using software Mimics 17.0 on the basis of primary CT data of all the patients.The correlation regression analysis was made between the revision rate and the approximate quantization value of Vx.The Glasgow Coma Score (GCS) of conscious state was used to evaluate the 39 patients after failure of their primary surgery before the surgical strategy for revision was worked out.The cobb angle,pelvic incidence angle (PI),pelvic inclination angle (PT),sacral inclination angle (SS),sagittal deviation (SVA),pain visual analogue scale (VAS) were measured and recorded before operation and at the last follow-up for the KP/VP revision group and internal fixation revision group,indicated as △cobb,△PI,△PT,△SS,△SVA and △VAS,respectively.The indexes were compared between the 2 groups.Results The incidence of osteoporotic vertebral fractures treated with internal fixation revision was 1.18％ (8/676).The correlation between Vx and revision rate was y =0.53 + 0.04x (P ＜ 0.05).The regression analysis showed that Vx was positively correlated with the revision rate (r2 =0.860,P =0.001) and the fitting curve was correlated (r2 =0.916,P =0.001).The GSC scores revealed 31 normal,6 mild disturbance and 2 moderate disturbance cases.There were no significant differences in gender,age or VAS scores between the KP/VP revision group and the internal fixation revision group (P ＞ 0.05).There was a significant difference in △cobb between the 2 revision groups (6.3° ± 7.5° versus 19.2° ± 14.8°) (P ＜0.05),but there were no significant differences between the 2 groups in △PI (4.1°±5.2° versus 3.3°±6.7°),△PT (0.7°±4.6° versus 0.4° ± 3.2°),△SS (3.7° ± 6.2° versus 3.1° ± 5.3°) or △SVA (-3.2 ± 11.9 mm versus-7.9 ± 9.5 mm) (P ＞ 0.05).Conclusions The outcomes of primary PKP/PVP have a great impact on the decision-making of internal fixation revision.The mode and extent of diffusion after initial vertebral cement perfusion are particularly related to the revision rate.The revision plan should depend on clinical symptoms.The internal fixation revision should be individualized to ensure the quality of life of the patients in line with the principles of "resolving symptoms" and "moderate correction".

Objective To investigate the relationship between iodine nutritional status and thyroid hormone levels,and to provide a guideline for monitoring iodine nutrition and thyroid function.Methods A crosssectional survey was performed by randomly selecting 341 samples (health pregnant women with a first child) from the Second People's Hospital of Guiyang,Bihai Community Medical Center and Jinhuayuan Community Center from October 2015 to September 2016.Levels of serum hormones and antibodies relative to throid of pregnant women in Guanshan Lake District of Guiyang at different pregnant times,which included throid stimulating hormone (TSH),free three triiodothyronine (FT3),free thyroxine (FT4),thyroid peroxidase antibody (TPOAb),and thyroglobulin antibody (TgAb),were measured by the electrochemical luminescence method,and urinary iodine levels were measured by heat digestion.Results The median urinary iodine of pregnant women at early,middle and late stages (T1,T2 and T3 stages) were 191.8,198.9 and 214.5 μg/L,respectively.FT3 increased first and then decreased during pregnancy.Levels of FT3 in the T2 stage were significandy higher than those in T1 and T3 stages (FT3 medians at the three stages were 4.49,4.83 and 4.57 pmol/L),and the differences were statistically significant (P ＜ 0.05).FT4 levels decreased during pregnancy (FT4 medians at the three stages were 16.32,14.65 and 13.22 pmol/L),and the differences among the three groups were statistically significant (H =67.517,P ＜ 0.01).Statistically significant differences were not found in the TSH levels among the three groups ~SH medians at the three stages were 2.05,2.01 and 2.39 mU/L,H =1.297,P ＞ 0.05).The medians of TPOAb and TgAb during T2 stage (9.60 and 19.02 U/ml) were significantly lower than those of other groups (18.92 and 24.75 U/ml at stage T1,and 13.46 and 22.06 U/ml at stage T3),and the differences were statistically significant (P ＜ 0.05).TSH levels were consistent with urinary iodine levels.TSH levels in the excessive iodine group (urine iodine:250 ～ 499 μg/L,2.54 mU/L) were significantly higher than those in the adequate iodine group (urine iodine:150 ～ 249 μg/L,1.97 mU/L) and deficient iodine group (urine iodine:＜ 150 μg/L,1.91 mU/L),and the differences were statistically significant (P ＜ 0.05).No correlations were found between levels of FT3,FT4,TPOAb,TgAb and levels of the urinary iodine.There was a significant positive correlation between urinary iodine levels and TSH levels (rs =0.180,P ＜ 0.01).The incidence of abnormal thyroid function in pregnant women was 29.33％ (100/341),which was composed of clinical hypothyroidism (accounting for 0.88％,3/341),subclinical hypothyroidism (accounting for 25.51％,87/341),low T4 level (accounting for 1.76％,6/341),clinical hyperthyroidism (accounting for 0.59％,2/341),subclinical hyperthyroidism (accounting for 0.59％,2/341),and TPOAb positive and TgAb positive (accounting for 12.61％,43/341).These abnormalities occurred mainly in the T1 and T3 stages.The prevalence of subclinical hypothyroidism increased with increasing of urinary iodine level,and the difference was statistically significant (x2 =11.269,P ＜ 0.05).Conclusion There is a positive correlation between pregnancy iodine nutritional status and its TSH level,so it is important to monitor the level of urinary iodine during pregnancy and to screen the thyroid function and antibodies in the early and middle time of pregnancy.