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 trends in mortality and life loss due to falls among the elderly in Wenzhou City, Zhejiang Province, so as to provide the basis for formulating prevention and control measures for falls among the elderly. Methods: The data on fall-related deaths among the elderly aged 60 and above in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2015 to 2023. The crude mortality was calculated and standardized using the data from the Sixth National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL), average years of life lost (AYLL), and potential years of life lost rate (PYLLR). The trends in mortality and life loss among the elderly were analyzed using the annual percent change (APC) and average annual percent change (AAPC). Results: There were 11 378 deaths due to falls among the elderly in Wenzhou City from 2015 to 2023, with a crude mortality of 82.67/100 000 and a standardized mortality of 65.32/105, which appeared no significant changing trend (AAPC=3.401%、2.995%,both P>0.05). There was a tendency towards a rise from 2019 to 2023 (APC=12.592%、11.507%, both P<0.05). The majority of falls occurred at home, with 6 312 cases accounting for 55.48%. The primary types of fall-related deaths were slips, trips, and falls on the same level, with 8 541 cases representing 75.07%. The crude mortality and standardized mortality of falls in males were 76.63/105 and 60.86/105, which were lower than that in females at 88.72/100 000 and 70.33/100 000 (both P<0.05), and the trends were consistent with the overall population. The crude mortality of falls among the elderly increased with age (P<0.05). From 2015 to 2023, the crude mortality of falls among the elderly aged 60 to <65 years showed an upward trend (AAPC=4.860%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). The PYLL was 5 123 person-years, the AYLL was 0.45 years per person, and the PYLLR was 0.37‰. From 2015 to 2023, PYLL showed an upward trend (AAPC=5.477%, P<0.05). The PYLL, AYLL, and PYLLR for males were 3.08 times, 3.48 times, and 2.67 times those of females, respectively. Conclusions From 2015 to 2023, the mortality of falls among the elderly in Wenzhou City had remained relatively stable. However, PYLL showed an upward trend. Males and older seniors were key groups for falls prevention. It is recommended to enhance health education and promote age-friendly home modifications to prevent falls among the elderly.

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 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 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.

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.

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 explore the diagnostic value of strain ultrasonic elastography (SUE) supported by Image Pro Plus (IPP) software in distinguishing benign and malignant Breast Imaging Reporting and Data System (BI-RADS) category 4 nodules.Methods:The clinical and ultrasound imaging data of 192 female patients with BI-RADS category 4 nodules diagnosed by breast ultrasound in Tianjin Medical University Cancer Institute and Hospital from January 2020 to January 2021 were retrospectively analyzed. One nodule was selected for each patient, and a total of 192 nodules were analyzed. The ultrasound images and SUE images of each nodule were acquired before surgery, followed by BI-RADS classification scoring and SUE scoring. The IPP software was applied to outline the region of interest of all nodules, and the software automatically counted the SUE area ratio (SUE-IPP-AR) of all nodules. Using pathological diagnosis as the gold standard, SUE-IPP scoring was performed based on the optimal cut-off value of SUE-IPP-AR for distinguishing benign and malignant nodules according to receiver operating characteristic (ROC) curve. The efficacy of BI-RADS classification, SUE score, SUE-IPP score, and SUE-IPP+BI-RADS combined score in the differentiation of benign and malignant breast nodules were analyzed by ROC curve. Kappa coefficient was used to assess inter-observer agreement for SUE and SUE-IPP-AR.Results:Of the 192 nodules, 58 were benign nodules and 134 were malignant nodules diagnosed by pathology. These nodules were classified by BI-RADS, with 46 nodules in BI-RADS category 4A, 57 nodules in BI-RADS category 4B and 89 nodules in BI-RADS category 4C. SUE images 1-6 level were 12, 14, 41, 51, 42, and 32 nodules, respectively. ROC curve analysis showed that the optimal cut-off value of SUE-IPP for determining benign and malignant BI-RADS category 4 breast nodules was 58% [area under the curve (AUC) = 0.729, sensitivity 73%, specificity 69%]. The AUC of SUE-IPP+BI-RADS combined score for determining benign and malignant nodules was the largest (0.871), which was higher than that of BI-RADS score (AUC = 0.829, Z = 2.51, P = 0.012), SUE-IPP score (AUC = 0.729, Z = 3.56, P < 0.001) and SUE score (AUC = 0.695, Z = 4.37, P < 0.001). The sensitivity of SUE-IPP+BI-RADS combined score ≥ 3 points for diagnosing malignant nodules was 86.6%, while the specificity was 82.8%. Therefore, SUE-IPP+ BI-RADS score had the best efficacy for determining benign and malignant nodules. There was good agreement between sonographer with more than 5 years of experience and those with less than 5 years of experience in applying SUE to diagnose breast malignant nodules (Kappa = 0.768, 95% CI 0.711-0.825), and very good diagnostic agreement in applying SUE-IPP (Kappa = 0.946, 95% CI 0.919-0.974). Conclusions:SUE-IPP can improve the diagnostic ability for BI-RADS category 4 breast malignant nodules and can be used as an adjunct to ultrasound diagnosis.