ObjectiveTo dynamically observe and evaluate the damage to the pulmonary air-blood barrier in mice during the inflammatory cancer transformation process of ulcerative colitis （UC） based on the "lung-intestine correlation" theory. MethodsSixty-five C57BL/6 mice were divided into a normal group （n=25） and a model group （n=40） using a random number table. Azoxymethane/dextran sodium sulfate （DSS） method was used to establish a mouse model of UC inflammation cancer transformation in the modeling group. According to the tissue collection time points at 5， 8， 11， 13， and 15 weeks， the normal group mice were randomly divided into the normal 5w， 8w， 11w， 13w， and 15w groups. The model group mice， 10 mice of which died after the first cycle of DSS administration， were randomly divided into model 5w， 8w， 11w， 13w， and 15w groups. During the experiment， the general condition of the mice was observed daily， and their body weight was measured weekly. At the corresponding tissue collection time points， the colon length of each group was measured. Histopathology of mouse lung and colon tissues was examined using HE staining. Immunofluorescence was used to detect changes in the positive expression of tight junction protein （ZO-1）， vascular endothelial cadherin （VE-cadherin）， and cytoskeletal protein （F-actin） in lung and colon tissues. RT-PCR was used to detect the mRNA expression of apoptosis regulatory proteins B-cell lymphoma-2 （Bcl-2）， BCL2-associated X protein （Bax）， and Cysteine aspartic acid protease-3 （Caspase-3） in lung tissues. Western Blot was employed to measure protein levels of ZO-1， VE-cadherin， and F-actin in lung tissues. ResultsCompared to the normal group at the same time point， the mice in the model group at each time point generally had poorer conditions， with weight loss and shortened colon length （P＜0.05 or P＜0.01）. In the model 5w group， there was significant inflammatory cell infiltration in the colon tissue； in the model 8w group， there was mild atypical hyperplasia； in the model 11w group， the crypt structure was disordered， and moderate to severe atypical hyperplasia occurred； in the model 13w and 15w groups， tumors appeared. Pulmonary interstitial lesions， inflammation， vasculitis， and fibrosis were observed at all stages of UC inflammation cancer transformation. The protein levels of ZO-1， VE-cadherin， and F-actin， as well as Bcl-2 mRNA expression in lung tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period， while the expressions of Bax and Caspase-3 mRNA increased； the expressions of ZO-1， VE-cadherin， and F-actin proteins in colon tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period （P＜0.01 or P＜0.05）. Compared to the model 5w group， the ZO-1 and F-actin protein levels and Bcl-2 mRNA expression in lung tissue in the other model groups increased in the atypical hyperplasia period and canceration period， while the expressions of Bax and Caspase-3 mRNA decreased； the expression of ZO-1 protein in colon tissue increased in the canceration period， and the expression of VE-cadherin protein decreased in the atypical hyperplasia period （P＜0.01 or P＜0.05）. ConclusionIn the process of "inflammatory response-atypical hyperplasia-carcinogenesis" in UC inflammatory cancer transformation mice， there were damage to air-blood barrier.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.

ObjectiveTo observe the real‑world effectiveness and economic outcomes of Weishi Qingjin Formula （苇石清金方， WQF） in the treatment of adult community‑acquired pneumonia （CAP） with phlegm‑heat obstructing the lung syndrome. MethodsBased on a multicenter， real-world retrospective cohort study， clinical data were collected from hospitalized adult patients diagnosed with non‑severe CAP and phlegm‑heat obstructing the lung syndrome in 10 traditional Chinese medicine （TCM） hospitals in Jiangsu province. Patients were divided into an exposure group （those who received oral WQF） and a non‑exposure group （those who did not）. The following outcomes were compared between the two groups before and after treatment， which were remission rates of clinical symptoms including cough， expectoration （sputum volume， color， consistency）， and chest pain， levels of inflammatory markers including C‑reactive protein （CRP） and white blood cell count （WBC）， and the rate of pulmonary inflammatory absorption on chest CT. Subgroup analyses were performed based on age， gender， smoking status， presence of hypertension， and the severity of community-acquired pneumonia （CURB‑65） score， comparing the two groups in terms of cough remission rate， chest pain remission rate， and chest CT absorption rate. For health economic evaluation， cost‑effectiveness analysis was used to calculate the cost‑effectiveness ratio （CER） and incremental cost‑effectiveness ratio （ICER）. Univariate sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the results. ResultsA total of 647 patients in the exposure group and 1491 patients in the non-exposure group were included in the final statistical analysis. There was no statistically significant difference in length of hospital stay， gender， marital status， smoking history， bronchoscopy history， and comorbidities between the groups （P＞0.05）， but age， CURB-65 score， and antibiotic use. The exposure group had significantly higher remission rates of cough and sputum consistency than the non-exposure group （P＜0.05）. After adjusting for confounders using propensity score matching and logistic regression， the cough remission rate in the exposure group was 1.49 times that of the non-exposure group （P＜0.01）. No significant difference was observed between groups in the reduction rates of CRP and WBC， and in the rate of pulmonary inflammatory absorption on chest CT （P＞0.05）. Subgroup analyses revealed that the cough remission rate in the exposure group was significantly better than that in the non-exposure group except for patients aged ≥65 years， smokers， hypertensive patients， those using other type antibiotics or not using antibiotics， and those with a CURB-65 score ≥1 （P＜0.05）. Among smokers， the chest pain remission rate in the exposure group was 4.38 times that of the non-exposure group （P＜0.01）. No significant difference in chest CT absorption rate was found between groups across subgroups of gender， age， hypertension status， or antibiotic type （P＞0.05）. In terms of economic evaluation， CER was 10,877.60 CNY/case in the exposure group and 16,773.10 CNY/case in the non-exposure group. Compared to the exposure group， the non-exposure group incurred an additional 15,034.26 CNY to achieve one case of cough resolution， indicating a more favorable cost-effectiveness profile. Probabilistic sensitivity analysis yielded results consistent with the cost-effectiveness analysis， confirming the robustness of the findings. ConclusionWQF demonstrates significant efficacy in improving cough symptoms in the treatment of adult CAP with phlegm-heat obstructing the lung syndrome， and also exhibits favorable economic benefits.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.

ObjectiveTo observe the real‑world effectiveness and economic outcomes of Weishi Qingjin Formula （苇石清金方， WQF） in the treatment of adult community‑acquired pneumonia （CAP） with phlegm‑heat obstructing the lung syndrome. MethodsBased on a multicenter， real-world retrospective cohort study， clinical data were collected from hospitalized adult patients diagnosed with non‑severe CAP and phlegm‑heat obstructing the lung syndrome in 10 traditional Chinese medicine （TCM） hospitals in Jiangsu province. Patients were divided into an exposure group （those who received oral WQF） and a non‑exposure group （those who did not）. The following outcomes were compared between the two groups before and after treatment， which were remission rates of clinical symptoms including cough， expectoration （sputum volume， color， consistency）， and chest pain， levels of inflammatory markers including C‑reactive protein （CRP） and white blood cell count （WBC）， and the rate of pulmonary inflammatory absorption on chest CT. Subgroup analyses were performed based on age， gender， smoking status， presence of hypertension， and the severity of community-acquired pneumonia （CURB‑65） score， comparing the two groups in terms of cough remission rate， chest pain remission rate， and chest CT absorption rate. For health economic evaluation， cost‑effectiveness analysis was used to calculate the cost‑effectiveness ratio （CER） and incremental cost‑effectiveness ratio （ICER）. Univariate sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the results. ResultsA total of 647 patients in the exposure group and 1491 patients in the non-exposure group were included in the final statistical analysis. There was no statistically significant difference in length of hospital stay， gender， marital status， smoking history， bronchoscopy history， and comorbidities between the groups （P＞0.05）， but age， CURB-65 score， and antibiotic use. The exposure group had significantly higher remission rates of cough and sputum consistency than the non-exposure group （P＜0.05）. After adjusting for confounders using propensity score matching and logistic regression， the cough remission rate in the exposure group was 1.49 times that of the non-exposure group （P＜0.01）. No significant difference was observed between groups in the reduction rates of CRP and WBC， and in the rate of pulmonary inflammatory absorption on chest CT （P＞0.05）. Subgroup analyses revealed that the cough remission rate in the exposure group was significantly better than that in the non-exposure group except for patients aged ≥65 years， smokers， hypertensive patients， those using other type antibiotics or not using antibiotics， and those with a CURB-65 score ≥1 （P＜0.05）. Among smokers， the chest pain remission rate in the exposure group was 4.38 times that of the non-exposure group （P＜0.01）. No significant difference in chest CT absorption rate was found between groups across subgroups of gender， age， hypertension status， or antibiotic type （P＞0.05）. In terms of economic evaluation， CER was 10,877.60 CNY/case in the exposure group and 16,773.10 CNY/case in the non-exposure group. Compared to the exposure group， the non-exposure group incurred an additional 15,034.26 CNY to achieve one case of cough resolution， indicating a more favorable cost-effectiveness profile. Probabilistic sensitivity analysis yielded results consistent with the cost-effectiveness analysis， confirming the robustness of the findings. ConclusionWQF demonstrates significant efficacy in improving cough symptoms in the treatment of adult CAP with phlegm-heat obstructing the lung syndrome， and also exhibits favorable economic benefits.

Objective To evaluate and improve missing data imputation methods to enhance the performance of binary classification prediction model.Methods By simulating data missing scenes,the effects of direct elimination,mean imputation,random forest(RF)imputation algorithm,and multiple imputation-random forest(MI-RF)on the performance of the prediction model were jointly evaluated by receiver operating characteristic area under curve(AUC)and root mean square error(RMSE).Bayesian Network was introduced for the random forest imputation algorithm to optimize the imputation method using the correlations between variables.Results Under different missing proportions,both AUC and RMSE indicated that Bayesian network optimized random forest(BN-RF)imputation algorithm was better.In addition,when the missing proportion was 10％-20％,various imputation methods had roughly the same improvement effect for the prediction model;when the proportion of missing data was 30％-40％,compared to the mean imputation,except for the BN-RF,RF was more effective and its effect was slightly better than MI-RF;however,when the proportion of missing data was close to 50％,even if the model performance was still appropriate,the imputation data gradually deviated from the true data features,resulting in a decrease in the usability of the model.Conclusion The overall effect of BN-RF is satisfactory,and it should be chosen when random missing was 30％-40％.

ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Objective:To explore the association between childhood trauma and prefrontal cortex functional networks in early adulthood using functional near-infrared spectroscopy(fNIRS).Methods:Twenty-eight individu-als with childhood trauma comprised the trauma group,while 32 without trauma formed the control group.The Childhood Trauma Questionnaire(CTQ)assessed abuse and neglect,the Ruminative Responses Scale(RRS)meas-ured repetitive thinking about negative events,and the Iowa Gambling Task(IGT)evaluated decision-making tend-encies.fNIRS data collected during the IGT were used to calculate degree centrality(DC),betweenness centrality(BC),and local efficiency(LE)in prefrontal networks.Mediation analysis explored relationships among childhood trauma,brain function(DC,BC,LE),and ruminative thinking.Results:Compared to controls,the trauma group had decreased DC in bilateral dorsolateral prefrontal cortices,increased DC,BC,and LE in the right inferior frontal gy-rus,and elevated LE in the bilateral frontal poles.BC and LE in the right inferior frontal gyrus partially mediated the relationship between CTQ sexual abuse and RRS scores(48.57％and 41.43％,respectively).Conclusion:Child-hood trauma is significantly associated with changes in prefrontal network properties in early adulthood.Sexual a-buse,in particular,may influence emotional regulation and cognitive functions by altering the network attributes of the right inferior frontal gyrus.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To investigate the influencing factors of adverse reactions of reconstructive flaps after postoperative precision radiation therapy for head and neck tumors.Methods:Medical records of 46 patients who underwent radiotherapy after flap reconstruction for head and neck tumors in the Affiliated Hospital of Inner Mongolia Medical University between January 2016 and October 2022 were retrospectively analyzed. The overall survival (OS), local regional control (LRC) and dosimetric parameters after radiotherapy were analyzed. The adverse reactions mainly including radiation dermatitis and flap necrosis at 3 and 6 months after radiotherapy, flap atrophy, flap fibrosis, dysphagia and chewing dysfunction at 12 and 24 months after radiotherapy were recorded. Adverse reactions were graded using the common terminology criteria for adverse events (CTCAE) version 5.0. Quantitative data were analyzed by one-way analysis of variance or rank-sum test. Qualitative data were analyzed by chi-square test or Fisher's exact test. Multivariate analysis of influencing factors of adverse reactions was performed using binary logistic stepwise regression.Results:All 46 patients were aged 57.6 years on average. The median follow-up time was 65 months (12-100 months). After the follow-up, 22 patients died, 6 recurred, and 7 had distant metastases. The 5-year OS rate was 48% and 5-year LRC rate was 69%. The incidence of radiation dermatitis was decreased over time after the end of radiotherapy: 80% (37/46) and 65% (30/46) at 3 months and 6 months after radiotherapy, respectively. The incidence of grade 3 radiation dermatitis was 11% (5/46) and 0 at 3 and 6 months after radiotherapy, respectively. The incidence of grade 2 flap necrosis was 4% (2/46) at 3 months after radiotherapy. At 12 months after radiotherapy, the incidence of flap atrophy and fibrosis was 83% (38/46) and 67% (31/46) , and the incidence of grade 3 flap atrophy and fibrosis was equally 4% (2/46) , respectively. All patients had dysphagia and chewing dysfunction at 12 months after radiotherapy. At 24 months after radiotherapy, 83% (38/46) and 61% (28/46) of patients still had dysphagia and chewing dysfunction. Multivariate regression analysis showed that irradiated flap volume, total radiotherapy dose, pharyngeal constrictor D mean and pharyngeal constrictor V 60 Gy, the interval between surgery and radiotherapy, gender and age were the independent influencing factors of adverse reactions of reconstructive flaps after precision radiation therapy for head and neck tumors. Conclusions:For patients undergoing flap reconstruction for head and neck tumors, under the premise of ensuring tumor control, the dose to normal tissue and flap blood supply area should be strictly limited, the irradiated volume should be reduced, and the interval between surgery and radiotherapy should be shortened (≤6 weeks) to reduce the risk of adverse reactions. Hypo-fractionated radiotherapy plan should be formulated or the total radiotherapy dose should be appropriately adjusted for elderly patients to reduce long-term complications.