ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

The Internet of Bodies （IoB） refers to an embodied technology that treats the physical body as a network interface and embeds technological objects into the human body， aiming to collect massive body data. As an emerging technology， the widespread application of IoB in the field of smart healthcare will bring both advantages and disadvantages. It poses ethical risks in terms of physicality， psychology， and sociability， primarily manifested in the uncertainty of technology that may harm patients’ bodies， the easy restriction of patients’ autonomy by external technologies， and issues of fairness and equality caused by the technology gap. Faced with the realistic ethical dilemmas arising from IoB technology empowering smart healthcare， solutions were proposed across several levels. On the ethical mechanism level， an interdisciplinary and multi-field expert alliance should be established to promote the optimization of ethical governance mechanisms. In terms of ethical governance methods， a governance strategy prioritizing “pre-control” should be adopted to front-load ethical risks. On the practical application level， it was vital to clarify the reasonable application boundaries of technology in practice and integrate ethical morality into technology application behavior. Regarding social justice in technology resources， a dual approach of strengthening grassroots investment and educational guidance should be implemented to ensure ethical justice and accessibility in medical practice， thereby guiding the development of IoB technology to align with the fundamental principles of bioethics.

Background and purpose:The ripple filter(RiFi)is a passive energy modulator used in particle beam therapy to broaden the Bragg peak.The 1D-RiFi features a wavy structure that can broaden a monoenergetic carbon ion beam to 3 mm,while the 2D-RiFi employs a two-dimensional groove structure to achieve a 6 mm beam broadening.This study aimed to evaluate the potential advantages of the 2D-RiFi over the 1D-RiFi in terms of dose distribution optimization,treatment efficiency,and organ at risk(OAR)dose control by comparing water phantom and clinical patient plans.Methods:Carbon ion treatment plans were designed for water phantoms and 20 patients using both 1D-RiFi and 2D-RiFi.The water phantom plans targeted a cubic region of interest(80 mm×80 mm×80 mm)at ranges of 95,105,190 and 290 mm.From patients who underwent carbon ion therapy at Shanghai Proton and Heavy Ion Center,20 cases were selected via simple random sampling with computer-generated random numbers,stratified by the proportion of different tumor sites(6 head and neck tumors,4 prostate tumors,4 lung tumors,2 pancreatic tumors,2 liver tumors and 2 shoulder tumors).Key dosimetric metrics,including homogeneity index(HI),conformity index(CI)and clinical target volume(CTV)coverage by 95%prescription dose(V95),were analyzed along with OAR doses.Energy layers,beam time,and irradiation time were compared between the two RiFi types.Statistical analysis was performed using the Wilcoxon rank-sum test,with a significance level of P＜0.05.This study was approved by the ethics committee of Shanghai Proton and Heavy Ion Center(approval number:240311EXP-01).Results:For water phantom plans,the 1D-RiFi plans achieved HI of 0.04±0.01,CI of 1.10±0.03,V95 of 99.92%±0.06%and flatness of 6.52%±0.61%,while the 2D-RiFi plans achieved HI of 0.04±0.01,CI of 1.11±0.04,V95 of 99.92%±0.06%,and flatness of 7.52%±0.81%.The mean doses to the distal and lateral block in 1D-RiFi plans were(1.34 Gy±0.43)Gy[relative biological effectiveness(RBE)]and(0.98±0.05)Gy(RBE),respectively,compared to(1.47±0.33)Gy(RBE)and(0.94±0.03)Gy(RBE)for 2D-RiFi plans.The use of 2D-RiFi reduced the average beam-on time by 43%and the number of energy layers by 48%.For clinical plans,the 1D-RiFi plans had HI of 0.07±0.04,CI of 1.94±0.67,and V95 of 98.81%±1.61%,compared to HI of 0.07±0.05,CI of 1.95±0.70,and V95 of 98.79%±1.69%for the 2D-RiFi plans,with no statistically significant differences(P=0.77,0.65 and 0.66,respectively).OAR mean doses increased slightly with the 2D-RiFi plans(average increase of 0.8%,P=0.62)but remained within clinically acceptable limits.The 2D-RiFi plans reduced energy layers by 45%-50%(average 48%),beam time by 32%-49%(average 44%),and irradiation time by 28%-41%(average 36%).Conclusion:Treatment plans using the 2D-RiFi achieved comparable target coverage to those using the 1D-RiFi,with a slight but clinically acceptable increase in OAR doses.The application of the 2D-RiFi significantly reduced the number of energy layers,beam time and irradiation time in carbon ion therapy,enhancing treatment efficiency.

This study aims to investigate whether the dietary supplement coenzyme Q10(CoQ10)alleviates bisphenol A(BPA)-induced mouse Leydig cell line(TM3)damage through autophagy pathway.Cell activity was measured by CCK-8 assay when treated with different concentrations of BPA for 24 h.TM3 cells were then divided into 5 groups:CON group,BPA group,Torin2 group,CQ group and BPA+CoQ10 group,with three repeats in each group.The morphology of TM3 cells were observed under inverted light microscope.Western blot was used to determine the protein ex-pression of p62 and LC3-Ⅰ/Ⅱ.The autophagy level of TM3 cells was detected by MDC cell auto-phagy staining,the mRNA expression levels of Atg7,Beclin 1,p62 and Atg5 genes were deter-mined by RT-qPCR,and the apoptosis rate of TM3 cells was detected by flow cytometry.The results showed that compared with 0 μmol/L BPA treatment group,the viability of TM3 cells de-creased significantly after 24 h treatment with 60 μmol/L BPA(P＜0.01).Compared with CON group,the number of TM3 cells markedly reduced in the BPA-treated group,the expression of au-tophagy-related proteins(p62,LC3-Ⅱ)significantly increased(P＜0.01),comparable to the CQ group.The MDC fluorescence intensity dramatically enhanced(P＜0.01),the mRNA expression levels of autophagy-related genes(Atg7,Beclin1,p62,Atg5)significantly elevated(P＜0.01),and the apoptosis rate significantly increased(P＜0.01).Compared with BPA group,the expression levels of autophagy-related genes Atg7 and Beclin1 mRNA(P＜0.05),p 62 and Atg5 mRNA(P＜0.01)in TM3 cells treated with BPA+CoQ10 significantly decreased.Moreover,the expres-sion levels of autophagy-related protein p62(P＜0.01)and LC3-Ⅱ(P＜0.05),MDC fluorescence intensity(P＜0.05)and apoptosis rate(P＜0.01)also markedly reduced.In conclusion,CoQ10 could subsequently reduce the apoptosis of TM3 cells by improving the abnormal autophagy flux induced by BPA.

This study aims to investigate whether the dietary supplement coenzyme Q10(CoQ10)alleviates bisphenol A(BPA)-induced mouse Leydig cell line(TM3)damage through autophagy pathway.Cell activity was measured by CCK-8 assay when treated with different concentrations of BPA for 24 h.TM3 cells were then divided into 5 groups:CON group,BPA group,Torin2 group,CQ group and BPA+CoQ10 group,with three repeats in each group.The morphology of TM3 cells were observed under inverted light microscope.Western blot was used to determine the protein ex-pression of p62 and LC3-Ⅰ/Ⅱ.The autophagy level of TM3 cells was detected by MDC cell auto-phagy staining,the mRNA expression levels of Atg7,Beclin 1,p62 and Atg5 genes were deter-mined by RT-qPCR,and the apoptosis rate of TM3 cells was detected by flow cytometry.The results showed that compared with 0 μmol/L BPA treatment group,the viability of TM3 cells de-creased significantly after 24 h treatment with 60 μmol/L BPA(P＜0.01).Compared with CON group,the number of TM3 cells markedly reduced in the BPA-treated group,the expression of au-tophagy-related proteins(p62,LC3-Ⅱ)significantly increased(P＜0.01),comparable to the CQ group.The MDC fluorescence intensity dramatically enhanced(P＜0.01),the mRNA expression levels of autophagy-related genes(Atg7,Beclin1,p62,Atg5)significantly elevated(P＜0.01),and the apoptosis rate significantly increased(P＜0.01).Compared with BPA group,the expression levels of autophagy-related genes Atg7 and Beclin1 mRNA(P＜0.05),p 62 and Atg5 mRNA(P＜0.01)in TM3 cells treated with BPA+CoQ10 significantly decreased.Moreover,the expres-sion levels of autophagy-related protein p62(P＜0.01)and LC3-Ⅱ(P＜0.05),MDC fluorescence intensity(P＜0.05)and apoptosis rate(P＜0.01)also markedly reduced.In conclusion,CoQ10 could subsequently reduce the apoptosis of TM3 cells by improving the abnormal autophagy flux induced by BPA.

Objective To explore the impact factors of volume reduction rate(VRR)of benign thyroid nodules after thermal ablation based on conventional ultrasound and contrast-enhanced ultrasound(CEUS)manifestations.Methods Totally 238 patients with benign thyroid nodules who underwent thermal ablation were retrospectively enrolled and divided into VRR＜75%group(n=93)and VRR≥75%group(n=145)according to VRR of lesions 12 months after treatment.Multivariate logistic regression analysis was used to screen the independent impact factors of VRR of lesions 12 months after thermal ablation based on conventional ultrasound and CEUS manifestations.Receiver operating characteristic curve was plotted,the area under the curve(AUC)was calculated to evaluate the efficacy of the combination of the above factors for predicting VRR of lesions.Results High echo,calcification,cystic and solid components,high enhancement,enhancement loss and high ablation energy were all independent risk factors,while circular enhancement was the independent protective factor of VRR of benign thyroid nodules 12 months after thermal ablation(all P＜0.05).The AUC of combination of the above factors for predicting VRR of benign thyroid nodules 12 months after thermal ablation was 0.926.Conclusion High echo,calcification,cystic and solid components,high enhancement,enhancement loss and high ablation energy were all independent risk factors,while circular enhancement was the independent protective factor of VRR of benign thyroid nodules 12 months after thermal ablation.

Objective To explore the impact factors of volume reduction rate(VRR)of benign thyroid nodules after thermal ablation based on conventional ultrasound and contrast-enhanced ultrasound(CEUS)manifestations.Methods Totally 238 patients with benign thyroid nodules who underwent thermal ablation were retrospectively enrolled and divided into VRR＜75%group(n=93)and VRR≥75%group(n=145)according to VRR of lesions 12 months after treatment.Multivariate logistic regression analysis was used to screen the independent impact factors of VRR of lesions 12 months after thermal ablation based on conventional ultrasound and CEUS manifestations.Receiver operating characteristic curve was plotted,the area under the curve(AUC)was calculated to evaluate the efficacy of the combination of the above factors for predicting VRR of lesions.Results High echo,calcification,cystic and solid components,high enhancement,enhancement loss and high ablation energy were all independent risk factors,while circular enhancement was the independent protective factor of VRR of benign thyroid nodules 12 months after thermal ablation(all P＜0.05).The AUC of combination of the above factors for predicting VRR of benign thyroid nodules 12 months after thermal ablation was 0.926.Conclusion High echo,calcification,cystic and solid components,high enhancement,enhancement loss and high ablation energy were all independent risk factors,while circular enhancement was the independent protective factor of VRR of benign thyroid nodules 12 months after thermal ablation.

Background and purpose:The ripple filter(RiFi)is a passive energy modulator used in particle beam therapy to broaden the Bragg peak.The 1D-RiFi features a wavy structure that can broaden a monoenergetic carbon ion beam to 3 mm,while the 2D-RiFi employs a two-dimensional groove structure to achieve a 6 mm beam broadening.This study aimed to evaluate the potential advantages of the 2D-RiFi over the 1D-RiFi in terms of dose distribution optimization,treatment efficiency,and organ at risk(OAR)dose control by comparing water phantom and clinical patient plans.Methods:Carbon ion treatment plans were designed for water phantoms and 20 patients using both 1D-RiFi and 2D-RiFi.The water phantom plans targeted a cubic region of interest(80 mm×80 mm×80 mm)at ranges of 95,105,190 and 290 mm.From patients who underwent carbon ion therapy at Shanghai Proton and Heavy Ion Center,20 cases were selected via simple random sampling with computer-generated random numbers,stratified by the proportion of different tumor sites(6 head and neck tumors,4 prostate tumors,4 lung tumors,2 pancreatic tumors,2 liver tumors and 2 shoulder tumors).Key dosimetric metrics,including homogeneity index(HI),conformity index(CI)and clinical target volume(CTV)coverage by 95%prescription dose(V95),were analyzed along with OAR doses.Energy layers,beam time,and irradiation time were compared between the two RiFi types.Statistical analysis was performed using the Wilcoxon rank-sum test,with a significance level of P＜0.05.This study was approved by the ethics committee of Shanghai Proton and Heavy Ion Center(approval number:240311EXP-01).Results:For water phantom plans,the 1D-RiFi plans achieved HI of 0.04±0.01,CI of 1.10±0.03,V95 of 99.92%±0.06%and flatness of 6.52%±0.61%,while the 2D-RiFi plans achieved HI of 0.04±0.01,CI of 1.11±0.04,V95 of 99.92%±0.06%,and flatness of 7.52%±0.81%.The mean doses to the distal and lateral block in 1D-RiFi plans were(1.34 Gy±0.43)Gy[relative biological effectiveness(RBE)]and(0.98±0.05)Gy(RBE),respectively,compared to(1.47±0.33)Gy(RBE)and(0.94±0.03)Gy(RBE)for 2D-RiFi plans.The use of 2D-RiFi reduced the average beam-on time by 43%and the number of energy layers by 48%.For clinical plans,the 1D-RiFi plans had HI of 0.07±0.04,CI of 1.94±0.67,and V95 of 98.81%±1.61%,compared to HI of 0.07±0.05,CI of 1.95±0.70,and V95 of 98.79%±1.69%for the 2D-RiFi plans,with no statistically significant differences(P=0.77,0.65 and 0.66,respectively).OAR mean doses increased slightly with the 2D-RiFi plans(average increase of 0.8%,P=0.62)but remained within clinically acceptable limits.The 2D-RiFi plans reduced energy layers by 45%-50%(average 48%),beam time by 32%-49%(average 44%),and irradiation time by 28%-41%(average 36%).Conclusion:Treatment plans using the 2D-RiFi achieved comparable target coverage to those using the 1D-RiFi,with a slight but clinically acceptable increase in OAR doses.The application of the 2D-RiFi significantly reduced the number of energy layers,beam time and irradiation time in carbon ion therapy,enhancing treatment efficiency.

Objective:To construct a diabetes foot prediction model for adult patients with type 2 diabetes based on retrospective cohort study using data from a regional health data platform.Methods:Using Yinzhou Health Information Platform of Ningbo, adult patients with newly diagnosed type 2 diabetes from January 1, 2015 to December 31, 2022 were included in this study and divided randomly the train and test sets according to the ratio of 7∶3. LASSO regression model and bidirectional stepwise regression model were used to identify risk factors, and model comparisons were conducted with net reclassification index, integrated discrimination improvement and concordance index. Univariate and multivariate Cox proportional hazard regression models were constructed, and a nomogram plot was drawn. Area under the curve (AUC) was calculated as a discriminant evaluation indicator for model validation test its calibration ability, and calibration curves were drawn to test its calibration ability.Results:No significant difference existed between LASSO regression model and bidirectional stepwise regression model, but the better bidirectional stepwise regression model was selected as the final model. The risk factors included age of onset, gender, hemoglobin A1c, estimated glomerular filtration rate, taking angiotensin receptor blocker and smoking history. AUC values (95% CI) of risk outcome prediction at year 5 and 7 were 0.700 (0.650-0.749) and 0.715(0.668-0.762) for the train set and 0.738 (0.667-0.801) and 0.723 (0.663-0.783) for the test set, respectively. The calibration curves were close to the ideal curve, and the model discrimination and calibration powers were both good. Conclusions:This study established a convenient prediction model for diabetic foot and classified the risk levels. The model has strong interpretability, good discrimination power, and satisfactory calibration and can be used to predict the incidence of diabetes foot in adult patients with type 2 diabetes to provide a basis for self-assessment and clinical prediction of diabetic foot disease risk.

Objective:To develop a prediction model for the risk of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods:Patients with new diagnosis of T2DM recorded in Yinzhou Regional Health Information Platform between January 1, 2015 and December 31, 2022 were included in the study. The predictor variables were selected by using Lasso-Cox proportional hazards regression model. Cox proportional hazards regression models were used to establish the prediction model for the risk of DR. Bootstrap method (500 resamples) was used for internal validation, and the performance of the model was assessed by C-index, the receiver operating characteristic curve and area under the curve (AUC), and calibration curve.Results:The predictor variables included in the final model were age of T2DM onset, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, estimated glomerular filtration rate, and history of lipid-lowering agent and angiotensin converting enzyme inhibitor uses. The C-index of the final model was 0.622, and the mean corrected C-index was 0.623 (95% CI: 0.607-0.634). The AUC values for predicting the risk of DR after 3, 5, and 7 years were 0.631, 0.620, and 0.624, respectively, with a high degree of overlap of the calibration curves with the ideal curves. Conclusion:In this study, a simple and practical risk prediction model for DR risk prediction was developed, which could be used as a reference for individualized DR screening and intervention in newly diagnosed T2DM patients.