ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）/cysteinyl aspartate-specific proteinase （Caspase）-1/gasdermin D （GSDMD） signaling pathway. MethodsForty db/db mice were randomly assigned into model， positive control （0.001 3 g·kg·d^-1 dapagliflozin suspension）， and high-， medium-， and low-dose Gelian Tiaotang pills （3.12， 1.56， and 0.78 g·kg·d^-1 suspension of Gelian Tiaotang pills， respectively） groups， with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water， while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose （FBG） and body mass were measured every 4 weeks. Kidneys were weighed after sampling， and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The pathological changes， extracellular matrix deposition， and renal fibrosis degree were examined by hematoxylin-eosin， periodic acid-schiff （PAS）， and Masson staining， respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-1β and IL-18 in the renal tissue. Immunohistochemistry （IHC） was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， and GSDMD-N in the renal tissue. ResultsCompared with the normal group， the model group generally had poor general states and increases in the body mass， kidney weight， kidney index， and levels of FBG， TG， TC， SCr， and BUN （P<0.01）. In addition， glomerular pyknosis， increased matrix， vacuolar degeneration of renal tubular epithelial cells， and interstitial infiltration of inflammatory cells were observed in the model group （P<0.01）， together with rises in the levels of IL-1β and IL-18 in the renal tissue （P<0.01） and up-regulated protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.01）. Compared with the model group， 12 weeks of drug interventions reduced the body mass， kidney weight， and kidney index and lowered the levels of FBG， TG， TC， SCr， and BUN in the serum and IL-1β and IL-18 in the renal tissue （P<0.05， P<0.01）. Furthermore， drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.05， P<0.01）. The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway， thus delaying the process of renal fibrosis in diabetes.

Objective: To investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer. Methods: The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC). Results: Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05). Conclusions The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.

Objective: To investigate the mortality and life loss of female breast cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for prevention and control of breast cancer. Methods: Data of female breast cancer deaths in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management information System from 2014 to 2012. The mortality of breast cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010 (Chinese-standardized rate) and the world standard population first introduced by Segi (world-standardized rate). The life loss were measured using potential years of life lost (PYLL), rate of potential years of life lost (PYLLR) and average years of life lost (AYLL). The trends in mortality, PYLLR and AYLL were analyzed using the average annual percent change (AAPC). Results: Totally 2 523 deaths were reported due to breast cancer from 2014 to 2022, ranking fifth in the order of female malignant tumor deaths. The crude mortality of female breast cancer was 7.13/105, showing an increasing trend with AAPC of 2.186% (P<0.05). The Chinese population-standardized mortality and global population-standardized mortality were 5.93/105 and 4.39/105, showing no significant trend with AAPC of -0.617% and -0.602% (both P>0.05), respectively. The crude mortality of female breast cancer appeared a tendency towards a rise with age (P<0.05). The crude mortality of breast cancer in females aged 65 years and older showed an increasing trend (AAPC=3.283%, P<0.05), but there were no significant tendency aged 15 to <45 years and 45 to <65 years (AAPC=-1.011% and -1.850%, both P>0.05). The PYLL, PYLLR and AYLL of breast cancer were 41 227.50 person-years, 1.23‰ and 19.44 years per person, respectively. AYLL showed a decreasing trend (AAPC=-1.969%, P<0.05), and PYLLR showed no significant trend (AAPC=-0.527%, P>0.05). Conclusions The mortality of female breast cancer in Wenzhou City appeared a tendency towards a rise from 2014 to 2022, and AYLL appeared a downward trend. Females aged 65 years and older were the key groups for the prevention and control of breast cancer.

Objective: To analyze the trends in mortality of liver cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for improving liver cancer control measures. Methods: Data of liver cancer mortality in Wenzhou City from 2014 to 2022 were collected from Wenzhou Chronic Disease Monitoring Information System. The crude mortality were estimated and standardized by the national population census data in China in 2010, and the trends in mortality of liver cancer were analyzed with average annual percent change (AAPC). Results: There were 22 033 liver cancer deaths from 2014 to 2022, accounting for 18.08% of malignant tumor deaths and ranking the second in malignant tumor deaths. The crude mortality of liver cancer was 30.00/105 and the standardized mortality was 24.32/105, both showing decreasing trends (AAPC=-2.812% and -5.742%, both P<0.05). The standardized mortality of liver cancer were higher in men than in women (36.66/105 vs. 11.21/105, P<0.05), both showing decreasing trends (AAPC=-5.702% and -5.521%, both P<0.05). The crude mortality of liver cancer appeared a tendency towards a rise with age (P<0.05), with the highest crude mortality in the group aged 80 to 84 years, reaching 145.12/105. The crude mortality of liver cancer showed a tendency towards a decline among residents aged under 15 years, 15 to 44 years, 45 to 64 years and 65 years and above (AAPC=-20.311%, -6.569%, -7.408% and -3.177%, all P<0.05). Conclusions The mortality of liver cancer showed a tendency towards a decline in Wenzhou City from 2014 to 2022. Men and the elderly were high-risk groups for liver cancer deaths, and prevention should be strengthened based on risk factors.

Objective:To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma.Methods:A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel′s Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups.Results:(1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups ( Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions:Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

Diabetic kidney disease(DKD)is the leading cause of end-stage renal disease worldwide and one of the major microvascular complications of diabetes.The pathogenesis of DKD is multifactorial,and its pathological process involves multiple pathways.Ferroptosis is a regulatory cell death characterized by iron dependent lipid peroxidation.Recently,an increasing number of studies have shown that ferroptosis is a key driving factor for the occurrence and development of DKD and has been identified to play a crucial role in the occurrence,development,and treatment of various kidney diseases.Traditional Chinese medicine has unique advantages in preventing and delaying the progression of DKD due to the characteristics of multi-component,multi-target,and multi-pathway.This article focuses on summarizing the impact of key regulatory factors and signaling pathways of ferroptosis on the pathological process of DKD,as well as the research progress of traditional Chinese medicine in regulating ferroptosis key factors and pathways for preventing and treating DKD.The aim of this study is to provide new ideas for the clinical treatment of DKD and the development of new traditional Chinese medicine drugs.

Objective:To explore the predictive value of ultrasound-based radiomics for liver metastasis in pancreatic neuroendocrine tumors (pNEN).Methods:A retrospective analysis was conducted on clinical, pathological, and ultrasound data of 269 pNEN patients confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from January 2012 to June 2022, including 94 patients with liver metastasis and 175 without liver metastasis. The regions of interest (ROI) were delineated on the maximum diameter section of the tumor using ITKSNAP software, and radiomics features were extracted using Pyradiomics. Radiomics features with an intra-group correlation coefficient greater than 0.90 were retained, and the optimal features were selected using the maximum relevance minimum redundancy (MRMR) algorithm. The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3, and the random forest algorithm (Rfs) was used to predict pNEN liver metastasis. Three models were constructed, including the clinical ultrasound model, the radiomics model, and the comprehensive model that combined clinical ultrasound and radiomics features. The predictive performance of different models for pNEN liver metastasis was analyzed using the ROC curve, and the predictive performance of different models was compared using the Delong test.Results:A total of 874 features were extracted from the ROI, and 12 highly robust radiomics features were retained for model construction based on inter- and intra-observer correlation grading and feature selection. The area under curve(AUC), sensitivity, specificity, and accuracy of the radiomics model, the clinical ultrasound model, and the comprehensive model for predicting liver metastasis in pNEN patients were 0.800, 0.574, 0.789, 0.714; 0.780, 0.596, 0.874, 0.777; and 0.890, 0.694, 0.874, 0.810, respectively. The Delong test showed that the comprehensive model had the best predictive performance, with an AUC superior to that of radiomics model ( Z=3.845, P=0.000 12) and clinical ultrasound model ( Z=3.506, P=0.000 45). Conclusions:The radiomics model based on ultrasound has good performance in predicting liver metastasis in pNEN, and the comprehensive model that combines clinical ultrasound and radiomics features can further improve the predictive performance of the model.

Objective:To predict the clinical value of World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of clear cell renal cell carcinoma (ccRCC) pre-scholarly based on ultrasound imaging group.Methods:Clinical and ultrasound imaging data of patients with surgically pathologically confirmed ccRCC at Tianjin Medical University Cancer Institue and Hospital from January 2021 to October 2022 were retrospectively collected and divided into a low grade group (grade Ⅰ and Ⅱ, 105 cases) and a high grade group (grade Ⅲ and Ⅳ, 70 cases) using WHO/ISUP pathological grading criteria. The clear image of the largest diameter of the tumor was selected and imported into ITK-SNAP software for manual segmentation of the image and extraction of ultrasonographic radiomics features. The patients were randomly divided into a training group and a test group in the ratio of 7∶3, with 122 cases in the training group and 53 cases in the test group. Stable radiomics features were obtained by dimensionality reduction. The support vector machines (SVM) algorithm was applied to predict the pathological grading of ccRCC. Finally, a clinical-ultrasound imaging model, an ultrasonographic radiomics model and a comprehensive model combining the two were constructed. The predictive effects of the three models were analyzed by the area under the ROC curve (AUC). The performance of each model was evaluated by applying the calibration curve. The net benefit of patients was obtained by applying the decision curve.Results:A total of 873 radiomics features were extracted, and 10 features were finally obtained for model construction after dimensionality reduction. Final test results showed that the AUC, sensitivity, specificity and accuracy of the clinical-ultrasound imaging model were 0.68, 0.47, 0.78, 0.66. The AUC, sensitivity, specificity and accuracy of the ultrasonographic radiomics model were 0.74, 0.53, 0.88, 0.74. The AUC, sensitivity, specificity and accuracy of the comprehensive model were 0.84, 0.63, 0.86, 0.77. The AUC of the comprehensive model being larger than that of the clinical-ultrasound imaging model ( Z=-3.224, P=0.001) and ultrasonographic radiomics model ( Z=-2.594, P=0.009). The calibration curves showed that the comprehensive model was more stable than the other two models. The decision curve showed a higher net clinical benefit for the comprehensive model than for the other two models within a threshold of 0.1-1.0. Conclusions:The preoperative prediction of ccRCC pathological grading by the radiomics model based on ultrasound images is effective. The comprehensive model constructed by combining relevant clinical and ultrasound parameters has better performance, which can help predict ccRCC pathological grading preoperatively to a certain extent. It is crucial to help physicians choose the best management plan in the era of personalized medicine.

Objective:To investigate the prediction of National Institute of Healthy (NIH) risk stratification of gastrointestinal stromal tumor(GIST) based on clinical ultrasound model, ultrasonographic radiomics model and combined model by oral contrast enhanced ultrasonography.Methods:The clinical and ultrasound imaging data of 204 gastric GIST patients attending Tianjin Medical University Cancer Institute and Hospital from June 2021 to June 2022 were retrospectively analyzed, among whom a total of 101 patients with high and moderate NIH risk stratification GIST confirmed by postoperative pathology were included in the high risk group, and a total of 103 patients with low and extremely low NIH risk stratification GIST were in the low risk group. The ultrasound images of the largest diameter of the GIST were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from the ROI segmented images. The patients were randomly divided into training and validation sets in the ratio of 7∶3. The XGBoost of Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and combined model. Then the area under ROC curve (AUC), sensitivity, specificity, and accuracy were evaluated; the predictive ability of the three models was compared by Delong test. Calibration Curve was applied to evaluate the model performance, and the clinical Decision Curve Analysis was applied to determine the net benefit to patients.Results:A total of 578 ultrasonographic radiomics features were extracted from ROI, and 8 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. Finally, test results showed that AUC, sensitivity, specificity and accuracy of clinical ultrasound imaging model, ultrasonographic radiomics model and combined model were 0.75, 69.3%, 68.9%, 69.1%; 0.87, 79.2%, 81.6%, 80.4%; 0.91, 80.2%, 83.5%, 81.9%, respectively. Delong test showed that the difference of AUC between ultrasonographic radiomics model and clinical ultrasound imaging model was statistically significant ( Z=2.698, P<0.001), and the combined model was significantly better than clinical ultrasound imaging model ( Z=4.062, P<0.001) and ultrasonographic radiomics model ( Z=2.225, P=0.026). Calibration Curve showed the high performance of combined model, and Decision Curve Analysis showed the superior clinical usefulness of combined model. Conclusions:It is feasible to construct an ultrasonographic radiomics model for GIST NIH risk stratification based on oral contrast enhanced ultrasonography images, and the combined model has more advantageous diagnostic performance, which can identify high risk NIH GIST objectively and stably for clinical purposes.

ObjectiveTo validate the alleviating effect of Gegen Qinliantang （GGQLT） on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 （SIRT1）/forkhead transcription factor O1 （FoxO1） autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups， with 15 mice in each group. The groups included a normal group （physiological saline， 0.2 g·kg^-1）， a metformin group （0.2 g·kg^-1）， high-， medium-， and low-dose GGQLT groups （31.9， 19.1， 6.9 g·kg^-1）， and a model group （physiological saline， 0.2 g·kg^-1）. They were orally treated with corresponding drugs for eight weeks， once daily. Fasting blood glucose （FBG） was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and total cholesterol （TC） were measured using an automated biochemical analyzer. Fasting serum insulin （INS） levels were determined using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Western blot was used to detect the expression of Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1， FoxO1， Beclin-1， and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group， the model group showed significant increases in FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.01）， and significant increases in the expression of SIRT1， Beclin-1， LC3， and FoxO1 proteins in liver tissues （P<0.01）. Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group， the metformin group and the low-， medium-， and high-dose GGQLT groups showed significant decreases in serum FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.05， P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， LC3 （P<0.05， P<0.01）， and up-regulated FoxO1 protein （P<0.01）. Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group， the medium- and high-dose GGQLT groups showed significant decreases in FBG， FINS， and TG levels （P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， and LC3 in liver tissues （P<0.05， P<0.01）， and reduced FoxO1 protein （P<0.01）. The high-dose GGQLT group showed reduced HOMA-IR， TC， LDL-C， and HDL-C levels （P<0.05， P<0.01）. Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders， alleviate insulin resistance in db/db mice， and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.