ObjectiveTo investigate the therapeutic effects and mechanisms of modified Huangqi Jianzhong decoction （HQJZ） on gastric precancerous conditions （GPC）. MethodsIn the cell experiment， human gastric mucosal epithelial cells underwent malignant transformation induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPC （MC cells）. The cells were allocated into four groups： control ， model， low-dose HQJZ （HQJZ-L）， and high-dose HQJZ （HQJZ-H）. The control and model groups were cultured with the complete medium， while HQJZ-L and HQJZ-H groups received additional interventions with HQJZ at low （0.5 g·L^-1） and high （1.0 g·L^-1） doses， respectively. Cell counting kit-8 （CCK-8） assay was used to evaluate cytotoxicity， Transwell assay to assess cell invasion， Annexin V-FITC/PI staining to detect apoptosis， immunofluorescence assay to analyze reactive oxygen species （ROS） expression and mitochondrial autophagy， and Western blot to verify expression of proteins in key pathways. In the animal experiment， the GPC model was established in healthy BALB/c mice through MNNG induction. Twenty-four mice were allocated into four groups： control， model， HQJZ-L， and HQJZ-H. Control and model groups received normal saline （10 mL·kg^-1·d^-1） orally， while HQJZ-L and HQJZ-H groups were administrated with low-dose （6.24 g·kg^-1·d^-1） and high-dose （12.48 g·kg^-1·d^-1） HQJZ， respectively. After treatment， hematoxylin‑eosin （HE） staining and AB-PAS staining were performed to observe histopathological changes in the gastric tissue. Immunofluorescence assay was used to detect reactive oxygen species （ROS） and microtubule-associated protein 1 light chain 3 （LC3） levels in the gastric mucosa， TdT-mediated dUTP nick-end labeling （TUNEL） staining to assess apoptosis rates， and Western blotting and immunohistochemistry （IHC） to analyze the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， and foxhead box O3 （FoxO3）. ResultsCell viability assays showed that HQJZ dose-dependently reduced MC cell viability compared with the control group （P<0.05， P<0.01）. Transwell assays revealed that the model group exhibited enhanced cell invasion compared with the control group （P<0.05）. Compared with the model group， HQJZ treatment attenuated the cell invasion （P<0.05）. Gastric mucosal pathology in mice demonstrated that compared with the control group， the model group showed elevated HE and AB-PAS pathological scores （P<0.05）， while HQJZ treatment reduced these scores （P<0.05）. Transmission electron microscopy revealed increased mitochondrial number and volume in the model group compared with the control group. HQJZ treatment resulted in abnormal mitochondrial structure and significant alterations in rough endoplasmic reticulum morphology and distribution， presenting as dilated and hollow forms. Mitochondrial and apoptosis assessments indicated that compared with the control group， the model group exhibited enhanced Mito Tracker Green fluorescence （P<0.05）， no significant change in DCFH-DA fluorescence， Mito Tracker Red CMXRos fluorescence， ROS immunofluorescence， or malondialdehyde （MDA） level， increased GSH level （P<0.05）， enhanced LC3 fluorescence （P<0.05）， no significant change in apoptosis rate， and elevated ATP content in cells and mouse serum （P<0.05）. Compared with the model group， HQJZ treatment reduced Mito Tracker Green fluorescence （P<0.05）， increased DCFH-DA fluorescence， Mito Tracker Red fluorescence， MDA level， LC3 fluorescence， and apoptosis rate （P<0.05）， and decreased cellular ATP content （P<0.05）. The HQJZ-L group showed no significant change in ROS immunofluorescence or GSH level， whereas the HQJZ-H group demonstrated enhanced ROS immunofluorescence and glutathione （GSH） level （P<0.05）. Immunohistochemistry and Western blotting revealed that compared with the control group， the model group exhibited increased numbers of PCNA- and Ki67-positive cells （P<0.05） and elevated protein levels of FoxO3， sirtuin 1 （SIRT1）， and B-cell lymphoma 6 （Bcl-6） （P<0.05）. HQJZ treatment reduced the numbers of PCNA- and Ki67-positive cells （P<0.05） and lowered the protein levels of FoxO3， SIRT1， and Bcl-6 （P<0.05）. ConclusionHQJZ alleviates the progression of gastric precancerous lesions by regulating mitochondrial function via the FoxO3/ROS pathway and promoting apoptosis of GPC-malignant cells.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective: To explore the influencing factors of incident caries at age 5 among caries-free 3-year-old children in Beijing, construct a machine learning prediction model based on oral health behavioral data, and provide a scientific basis and practical tool for early risk identification, stratified prevention and control, and home-kindergarten-medical collaborative intervention of incident dental caries in preschool children. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and written informed consent was obtained from the guardians of the study participants and their guardians. Children with complete baseline data at age 3 and follow-up data at age 5 from Beijing public oral health programs were included. Oral examinations were conducted according to World Health Organization diagnostic criteria, and questionnaires were completed by guardians. Risk factors were screened by Logistic regression. The total sample was randomly divided into a test set (20%) and a validation set (80%). Five-fold cross-validation was performed on the validation set for model training and tuning, and the final model performance was evaluated on the test set. Four machine learning models—decision tree, random forest, Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM)—were constructed. Model performance was evaluated using the area under the curve (AUC), accuracy, and specificity. Shapley Additive Explanations (SHAP) was used for model interpretation. Results: The incidence of incident caries for 3 372 5-year-old children in Beijing was 50.96%. Multivariate logistic regression showed that parental caries, sleeping with milk, frequent feeding at night, no postprandial cleaning, high sugar intake, insufficient bedtime tooth brushing, and non-fluoride toothpaste use were significant risk factors (P < 0.05). Although all four machine learning models performed well, the XGBoost model performed the best (AUC = 0.806). Feature importance and SHAP analysis indicated that the frequency of bedtime tooth brushing, the frequency of candy consumption, and parental caries status were the top three predictors. Conclusion The XGBoost model based on oral health behaviors at age 3 can accurately predict the risk of incident caries in 5-year-old children in Beijing. Bedtime tooth brushing, sugar control, and parental oral health management are key points for caries prevention in preschool children.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

ObjectiveTo observe the prognosis effect of soluble programmed death ligand-1（sPD-L1） in treating patients with advanced lung adenocarcinoma treated with epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs） and the influence of Yiqi Yangyin Jiedu prescription. MethodA prospective cohort-controlled study was conducted to enroll patients treated with EGFR-TKIs in the first line of treatment，who were admitted to the Oncology Department of Longhua Hospital and Shanghai Chest Hospital from May 1^st， 2021 to June 30^th， 2023， and they were evaluated as non-progressive and identified with deficiency of Qi and Yin after one month of treatment. The patients were divided into an exposed group （EGFR-TKIs combined with Yiqi Yangyin Jiedu prescription） and a non-exposed group （EGFR-TKIs alone）according to whether or not they were treated with Yiqi Yangyin Jiedu prescription and were treated until disease progression， or death and intolerable adverse reactions occurred. The enzyme-linked immunosorbent assay （ELISA） was applied to detect the level of sPD-L1 in patients at the time of enrollment and disease progression，and Cox risk proportionality model was used to analyze the independent prognostic factors affecting disease progression of patients treated with EGFR-TKIs. ResultA total of 90 patients （39 in the exposed group and 51 in the non-exposed group） undergoing disease progression after EGFR-TKI treatment were enrolled. At the time of enrolment and after disease progression，the levels of serum sPD-L1 in the 90 patients were 12.06 （27.54） ng·L^-1 and 41.99 （62.93） ng·L^-1，respectively. Compared with that at the time of enrollment， the serum sPD-L1 level in the 90 patients was significantly increased after disease progression （P<0.01）. The serum sPD-L1 level in patients in the exposed group was 12.27 （24.78） ng·L^-1 and 29.57 （61.12）ng·L^-1 respectively at the time of enrolment and after disease progression. In the non-exposed group， patients had serum sPD-L1 levels of 11.81 （28.46） ng·L^-1 and 49.54 （74.12） ng·L^-1 respectively at the time of enrolment and after disease progression. Compared with that at the time of enrollment， the serum sPD-L1 level in the two groups of patients was significantly increased after disease progression （P<0.01）. In addition， compared with that in the non-exposed group， the sPD-L1 level in the exposed group was greatly reduced after disease progression（P<0.01）. Cox multifactorial analysis showed that sPD-L1 level and age at the time of enrolment were associated with patients' progression-free survival（PFS），and that low levels of sPD-L1 （<12.06 ng·L^-1） prolonged the PFS and reduced the risk of disease progression in patients treated with EGFR-TKIs compared with high levels of sPD-L1. ConclusionElevated sPD-L1 level is a poor prognostic factor for the long-term efficacy of EGFR-TKIs，and treatment with Yiqi Yangiin Jiedu prescription can down-regulate sPD-L1 level of patients treated with EGFR-TKIs.

Objective: To analyze the trend in burden of rheumatoid arthritis (RA) in China from 1990 to 2021, so as to provide insights into reducing the RA burden in China. Methods: Data of Global Burden of Disease Study 2021 were collected, and the incidence, mortality and disability-adjusted life years (DALY) of RA in China from 1990 to 2021 were analyzed and compared with global and different Socio-demographic Index (SDI) regions. The trend in burden of RA was analyzed using average annual percent change (AAPC). Results: The crude incidence rates of RA in China increased from 10.87/105 in 1990 to 17.38/105 in 2021, the crude mortality rates increased from 0.41/105 to 0.72/105, and the crude DALY rates increased from 34.26/105 to 58.61/105, with the increases of 59.98%, 77.95% and 71.06%, respectively. From 1990 to 2021, the standardized incidence rates of RA in China showed an increasing trend (AAPC=0.545%, P<0.05), the standardized mortality rates showed a decreasing trend (AAPC=-0.783%, P<0.05), and the standardized DALY rates showed no significant trend (AAPC=-0.017%, P>0.05). In 2021, the standardized incidence rate, standardized mortality rate and standardized DALY rate of RA were higher in females than in males; from 1990 to 2021, the standardized DALY rates of RA showed a decreasing trend in females (AAPC=-0.200%, P<0.05) and an increasing trend in males (AAPC=0.316%, P<0.05). The crude incidence rates of RA first increased and then decreased with age in 2021, reaching the highest in the age group of 75-<80 years at 34.36/105. Both the crude mortality rates and the crude DALY rates increased with age, reaching the highest in the age group of 95 years and older at 26.72/105 and 285.67/105, respectively. The standardized incidence rates and standardized DALY rates of RA in China in 2021 were lower than those in high SDI regions, while the standardized mortality rate was lower than that in medium-low SDI regions. Conclusions The burden of RA in China from 1990 to 2021 showed an upward trend, and was at a high level compared to different SDI regions. Higher disease burden of RA was seen in females and the elderly.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Purpose: Retroperitoneal sarcomas (RPS) are rare tumors that present unique challenges, often due to late presentation, and the proximity of critical organs makes complete surgical resection challenging. This study aimed to assess the feasibility of neoadjuvant short-course radiotherapy (SCRT) targeting margins-at-risk and to assess its potential impact on outcomes. Materials and Methods: This is a single-center, prospective, non-randomized feasibility study. SCRT was administered via image-guided volumetric modulated arc therapy, consisting of 5 fractions of daily radiotherapy followed by immediate surgery. As a starting dose, patients were prescribed 25 Gy in 5 fractions. For the escalation stage, patients were prescribed 30 Gy in 5 fractions. Only the presumed threatened surgical margins were delineated for large tumors. Results: Patients with either primary or recurrent RPS were recruited. Eight patients underwent SCRT but one patient did not have a resection as planned. Seven patients underwent surgical resection, of whom one passed away 3 months postoperative from a cardiac event. After a median follow-up of 20.5 months for the six postoperative survivors, there were no overt long-term toxicities and one patient relapsed out-of-radiotherapy-field. Conclusion SCRT to RPS with a margin boost followed by immediate surgery is worth investigating. A starting dose of 30 Gy in 5 fractions is recommended for further studies. Longer-term follow-up is necessary.