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 By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.

ObjectiveTo investigate the protective effect and underlying mechanisms of Yishen Huayu prescription （YSHYP） on transdifferentiation of mouse renal tubular epithelial cells （TCMK-1） induced by transforming growth factor-β₁ （TGF-β₁）. MethodsA transdifferentiation model was established by treating TCMK-1 cells with 10 μg·L^-1 TGF-β₁. Experimental groups were established using 2 μmol·L^-1 silent information regulator 1 （SIRT1） inhibitor EX527. These included the blank group， model group， YSHYP group （treated with 10% YSHYP-medicated serum）， valsartan group （treated with 10% valsartan-medicated serum）， EX527+TGF-β₁ group， EX527+YSHYP group， and EX527 group. Immunofluorescence was used to detect the protein localization of α-smooth muscle actin （α-SMA）， E-cadherin， and microtubule-associated protein light chain 3 （LC3）. Western blot and Real-time polymerase chain reaction （Real-time PCR） were used to assess the expression of proteins and mRNA related to transdifferentiation， autophagy， and associated signaling pathways. ResultsThe results from Real-time PCR and Western blot indicate that compared with those in the blank group， expression levels of α-SMA， ubiquitin-binding protein p62 （p62）， and acetylated forkhead box protein O1（Ac-FoxO1） were significantly increased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. Compared with that in the model group， the expression of α-SMA and p62 were significantly downregulated in the YSHYP and valsartan groups （P<0.05， P<0.01）. Ac-FoxO1 protein levels were significantly reduced in the YSHYP group （P<0.05）， while the valsartan group showed no significant changes in Ac-FoxO1 levels. Compared with the YSHYP group， the valsartan group showed significant differences in p62 mRNA， α-SMA， and p62 protein expression （P<0.05）. Compared with those in the blank group， LC3， Beclin1， SIRT1， and forkhead box protein O1 （FoxO1） expression levels were significantly decreased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. In the model and EX527+TGF-β₁ groups， E-cadherin expression levels were significantly reduced （P<0.01）， while the EX527 group showed no statistically significant change. Compared with the model group， E-cadherin， LC3， Beclin1， SIRT1， and FoxO1 expression levels were significantly increased in both the YSHYP and valsartan groups （P<0.01， P<0.05）. Compared with the YSHYP group， the valsartan group exhibited significant differences in LC3， SIRT1， and FoxO1 mRNA expression （P<0.05， P<0.01）. Immunofluorescence results were consistent with those of Western blot and Real-time PCR. ConclusionYSHYP may protect TCMK-1 cells by activating the SIRT1/FoxO1 pathway， thereby promoting autophagy and restoring the autophagy flux to reduce the extent of transdifferentiation of TCMK-1 cells.

ObjectiveTo investigate the protective effect and underlying mechanisms of Yishen Huayu prescription （YSHYP） on transdifferentiation of mouse renal tubular epithelial cells （TCMK-1） induced by transforming growth factor-β₁ （TGF-β₁）. MethodsA transdifferentiation model was established by treating TCMK-1 cells with 10 μg·L^-1 TGF-β₁. Experimental groups were established using 2 μmol·L^-1 silent information regulator 1 （SIRT1） inhibitor EX527. These included the blank group， model group， YSHYP group （treated with 10% YSHYP-medicated serum）， valsartan group （treated with 10% valsartan-medicated serum）， EX527+TGF-β₁ group， EX527+YSHYP group， and EX527 group. Immunofluorescence was used to detect the protein localization of α-smooth muscle actin （α-SMA）， E-cadherin， and microtubule-associated protein light chain 3 （LC3）. Western blot and Real-time polymerase chain reaction （Real-time PCR） were used to assess the expression of proteins and mRNA related to transdifferentiation， autophagy， and associated signaling pathways. ResultsThe results from Real-time PCR and Western blot indicate that compared with those in the blank group， expression levels of α-SMA， ubiquitin-binding protein p62 （p62）， and acetylated forkhead box protein O1（Ac-FoxO1） were significantly increased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. Compared with that in the model group， the expression of α-SMA and p62 were significantly downregulated in the YSHYP and valsartan groups （P<0.05， P<0.01）. Ac-FoxO1 protein levels were significantly reduced in the YSHYP group （P<0.05）， while the valsartan group showed no significant changes in Ac-FoxO1 levels. Compared with the YSHYP group， the valsartan group showed significant differences in p62 mRNA， α-SMA， and p62 protein expression （P<0.05）. Compared with those in the blank group， LC3， Beclin1， SIRT1， and forkhead box protein O1 （FoxO1） expression levels were significantly decreased in the model group， EX527+TGF-β₁ group， and EX527 group （P<0.01）. In the model and EX527+TGF-β₁ groups， E-cadherin expression levels were significantly reduced （P<0.01）， while the EX527 group showed no statistically significant change. Compared with the model group， E-cadherin， LC3， Beclin1， SIRT1， and FoxO1 expression levels were significantly increased in both the YSHYP and valsartan groups （P<0.01， P<0.05）. Compared with the YSHYP group， the valsartan group exhibited significant differences in LC3， SIRT1， and FoxO1 mRNA expression （P<0.05， P<0.01）. Immunofluorescence results were consistent with those of Western blot and Real-time PCR. ConclusionYSHYP may protect TCMK-1 cells by activating the SIRT1/FoxO1 pathway， thereby promoting autophagy and restoring the autophagy flux to reduce the extent of transdifferentiation of TCMK-1 cells.

Objective: To develop a modified calculation formula for renal tumor volume and tumor contact surface area (CSA) based on the modeling results of 3D Slicer software, and to create a webpage of the calculation formula for use. Methods: The general information and tumor anatomical data of 98 patients who underwent partial nephrectomy during Jan.2021 and Jul.2023 in the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed.The imaging data were input into 3D Slicer software in the form of Dicom files for tumor and ipsilateral kidney modeling to obtain tumor anatomical data.The relationship between tumor anatomical parameters and tumor volume and CSA was analyzed using multifactorial linear regression.The initial modified formulas (V2, C2) and the optimized modified formulas (V3, C3) for tumor volume over CSA were established, respectively, after insignificant variables were eliminated.The mean square error (MSE) and Akaike information criterion (AIC) of the modified and traditional formulas (V1, C1) were compared, and the formula with the smallest MSE and AIC was selected as the optimal tumor volume and CSA calculation formula.The median tumor volume and CSA obtained from 3D modeling were used as the cutoff values.The optimal formula and conventional formula were applied to calculate tumor volume and CSA for all patients, and risk stratification was performed for all patients based on these cutoff values, and the perioperative indicators of patients in the upper and lower groups were compared.Finally, an online calculation tool was developed based on HTML. Results: Based on multifactorial linear regression analysis, we obtained the modified tumor volume calculation formula: V=0.382abc+2.488a+2.372b－4.146c+1.948（V2）, V=0.469abc－4.586c+13.816（V3）; the modified tumor CSA calculation formula CSA=2.469a －2.262L －19.23a+6.206b+1.212c+18.017L+1.616h－3.97h －2.185h/h －0.388（C2）, CSA=2.376a －2.144L －20.157a+5.024b+1.128c+17.578L+2.525h－2.634（C3）.Both of the modified volume formula (MSE=151.298 vs. 127.807 vs. 104.106) and modified CSA formula (MSE=309.878 vs.23.556 vs.30.388) had smaller errors compared to the conventional formula.The modified volume calculation formula showed that bleeding was more and thermal ischemia time was longer in patients with larger tumor volumes than in patients with smaller tumor volumes (P<0.05); and the modified CSA calculation formula showed that bleeding was more, surgery and thermal ischemia time were longer in patients with high CSA than in patients with low CSA (P＜0.05).Finally, V3 and C3 are selected as the best calculation formula, and a web page (https://lizihao-bot.github.io/RCC-Calculate/) was established for easy use. Conclusion: This study combined data from a medical information technology platform with numerical modeling methods to provide a faster and more accurate method to calculate the renal tumor volume and CSA.Meanwhile, a webpage version of the tool was developed to enhance its practicability.

This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods* ; Male ; Animals ; Swine ; Acupuncture Points ; Humans ; Swine, Miniature ; Needles

OBJECTIVE To construct ensemble learning models for predicting high-use days of budesonide based on meteorological factors， thereby providing reference for hospital pharmacy management. METHODS Meteorological data for 2024 and outpatient budesonide usage data from the jurisdiction of Sanming Hospital of Integrated Traditional Chinese and Western Medicine were collected. High-use days were defined as the 75th percentile of outpatient budesonide usage， and a corresponding dataset was established. The prediction task was formulated as a classification problem， and three ensemble learning models were developed： Random Forest， Extreme Gradient Boosting （XGBoost）， and Histogram-based Gradient Boosting Classifier. Model performance was evaluated using accuracy， precision， recall， F1-score， and log-loss. Model interpretability was analyzed using Shapley Additive Explanations （SHAP）. RESULTS The Histogram-based Gradient Boosting Classifier achieved the best performance （accuracy＝0.75， F1-score＝0.48）， followed by XGBoost （accuracy＝0.74， F1-score＝0.43） and Random Forest （accuracy＝0.72， F1-score＝0.22）. SHAP results suggested that the prediction results of the last two models have the highest correction. CONCLUSIONS Ensemble learning models can effectively predict high-use days of budesonide， with the Histogram- based Gradient Boosting Classifier demonstrating the best predictive performance. Low temperature， high humidity， and low atmospheric pressure show significant positive impacts on the prediction of daily budesonide usage.

BACKGROUND: Neoadjuvant immunochemotherapy has emerged as an indispensable therapeutic modality for non-small cell lung cancer (NSCLC). However, its clinical application experience remains limited, and the associations between various clinical factors and treatment benefits remain undefined. This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with stage IB-IIIB NSCLC in a real-world setting, analyze survival outcomes among subgroups with diverse clinical characteristics, and identify potential clinical predictive factors for pathological response. METHODS: This study included patients with stage IB-IIIB NSCLC who underwent radical lung resection after 2-4 cycles of neoadjuvant immunochemotherapy at Peking University People's Hospital between August 2019 and March 2024. Medical records and follow-up information were collected to analyze therapeutic response, adverse events and survival outcomes. Logistic analysis was used to identify clinical predictors of pathological response. RESULTS: Among 183 enrolled patients, 116 (63.4%) were stage III. Grade 3-4 immune-related adverse events (irAEs) occurred in 39 (21.3%) patients. Radiographic complete response (CR) or partial response (PR) was achieved in 118 (64.5%) patients. R0 resection was achieved in 180 (98.4%) patients. Major pathologic response (MPR) was observed in 107 (58.5%) patients, with 78 (42.6%) achieving pathologic complete response (pCR). Squamous cell carcinoma and radiographic objective response were associated with pathological response (pCR/MPR). With a median follow-up of 22.1 [interquartile range (IQR): 18.3-32.2] months, the 2-year event-free survival (EFS) and overall survival (OS) rates were 82.5% and 90.4%, respectively. Achievement of pathological response (pCR/MPR) was correlated with prolonged survival outcomes. CONCLUSIONS Neoadjuvant immunochemotherapy is safe and effective for patients with stage IB-IIIB NSCLC. Patients achieving pCR or MPR exhibit significantly better survival benefits from neoadjuvant immunochemotherapy. Squamous cell carcinoma and radiographic objective response can serve as clinical predictors of pathological response.
Humans ; Carcinoma, Non-Small-Cell Lung/mortality* ; Male ; Lung Neoplasms/mortality* ; Female ; Middle Aged ; Neoadjuvant Therapy/adverse effects* ; Aged ; Neoplasm Staging ; Adult ; Immunotherapy/adverse effects* ; Treatment Outcome ; Retrospective Studies

OBJECTIVES: Tiletamine, a veterinary anesthetic, has emerged as a novel psychoactive substance and has been abused in many parts of the world, causing great harm to public health. However, the sensitivity of existing detection methods cannot meet the needs of forensic practice. This study aims to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of tiletamine and its metabolite desethyltiletamine in human biological samples, and to verify its applicability in forensic practice. METHODS: SKF_525A was used as the internal standard. Biological samples were extracted with acetonitrile containing 1 ng/mL SKF_525A, vortexed for 10 min, ultrasonicated for 20 min, centrifuged at 10 000 r/min for 10 min, and 500 μL of the supernatant was filtered through a 0.22 μm membrane. Analyses were performed using an ACQUITY UPLC H-Class PLUS system and an XEVO TQ-S Micro triple quadrupole mass spectrometer. An ACQUITY UPLC^® BEH C18 (1.7 µm, 2.1 mm×100 mm) column at a flow rate of 0.3 mL/min was used, and four mobile phase systems were tested to optimize separation. Detection used positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, with quantifier ion transitions of mass to charge 224.043→179.016 for tiletamine and mass to charge 196.08→151.06 for desethyltiletamine. Calibration curves were established over 0.1-200 ng/mL in spiked blood samples. The linear range, limit of detection (LOD), and limit of quantification (LOQ) were determined. Low (5 ng/mL), medium (20 ng/mL), and high (100 ng/mL) concentrations of tiletamine were spiked into blood, liver, and kidney to evaluate precision, accuracy, matrix effect, recovery, and stability. Finally, actual forensic case samples were tested to validate applicability. RESULTS: The established UPLC-MS/MS method achieved simultaneous detection of tiletamine and desethyltiletamine in human biological samples, with retention times of 3.42 min and 2.82 min, respectively. Using mobile phase A (20 mmol/L ammonium acetate and 0.1% formic acid in water) and mobile phase B (acetonitrile) produced the best separation. In blood, tiletamine showed good linearity from 0.1-200 ng/mL (r=0.992, R²=0.983), LOD 0.03 ng/mL, LOQ 0.1 ng/mL, recovery 92%-107%, and matrix effect 71%-99%. In liver and kidney, recoveries were 91%-98% and 93%-104%, and matrix effects were 69%-96% and 72%-100%, respectively. Intra- and inter-day precision [expressed as relative standard deviation (RSD)] and accuracy [expressed as relative error (RE)] were within 15%, and samples were stable at -20 ℃. Tiletamine was detected in actual case samples at 0.37 μg/mL (blood), 0.15 μg/g (liver), 0.11 μg/g (kidney) in case 1, and 8.75 ng/mL (blood) in case 2; desethyltiletamine was also detected in blood. CONCLUSIONS The UPLC-MS/MS method is efficient, accurate, and sensitive, and is suitable for detecting tiletamine and desethyltiletamine in human biological samples.
Tandem Mass Spectrometry/methods* ; Humans ; Chromatography, High Pressure Liquid/methods* ; Substance Abuse Detection/methods* ; Liquid Chromatography-Mass Spectrometry