ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

Objective To analyze the incidence of congenital syphilis in four regions of China from 2005 to 2020 and predict its change trend, and to provide a scientific basis for the prevention and control of congenital syphilis. Methods The incidence data of congenital syphilis in eastern, western, central and northeastern China from 2005 to 2020 were collected. The annual change percentage (APC) and average annual change percentage (AAPC) were calculated by Joinpoint software, and the change trend was analyzed. The ARIMA model was established by SPSS26.0 software to predict the incidence from 2021 to 2025. Results From 2005 to 2020, there were 107 504 cases of congenital syphilis, and the incidence reached the peak in 2011, which was 0.90/100 000, and decreased to 0.09/100 000 in 2020. The incidence of congenital syphilis in the eastern, central, western, and northeastern regions of China decreased to 0.07/100 000, 0.06/100 000, 0.12/100 000, and 0.15/100 000 in 2020, respectively. Joinpoint regression analysis found that from 2005 to 2020, the incidence of congenital syphilis showed a downward trend in the whole country (AAPC=-8.68%, t=-5.18, P＜0.05), the eastern region (AAPC=-12.01%, t=-6.81, P＜0.05), the central region (AAPC=-5.45%, t=-2.09, P＜0.05), and the western region (AAPC=-6.05%, t=-3.00, P＜0.05), while the incidence in the northeast region was relatively stable (AAPC=-1.66%, t=-1.18，P＞0.05). The ARIMA (2,2,0) model was constructed to predict that the annual incidence of congenital syphilis from 2021 to 2025 would be 0.06/100,000, 0.03/100,000, 0.02/100,000, 0.01/100,000, and 0.01/100,000, respectively. Conclusion From 2005 to 2020, the incidence of congenital syphilis in China shows an overall downward trend. The western and northeastern regions are the key prevention and control areas, and the work of ^"eliminating mother to child transmission of syphilis^" needs to be continuously promoted.

Objective: To analyze the impact of premature death due to four major chronic diseases on life expectancy in Yangpu District, Shanghai Municipality from 2010 to 2021, so as to provide the evidence for formulating chronic disease prevention and control strategies. Methods : Mortality data of registered residents in Yangpu District from 2010 to 2021 were collected through the Death Information Registration and Management System of the Shanghai Municipal Disease Control and Prevention Information Management Platform. The premature death probability of malignant tumors, diabetes, cardiovascular and cerebrovascular diseases, and chronic respiratory diseases, and life expectancy of residents were calculated using the abridged life table method. Trends in premature death probability for four types of chronic diseases were analyzed using the average annual percent change (AAPC). The impact of premature death probability due to four chronic diseases on life expectancy was assessed by Arriaga's decomposition method. Results : The premature death probability due to four major chronic diseases in Yangpu District decreased from 9.88% in 2010 to 9.22% in 2021, showing an overall declining trend (AAPC=-0.540%, P<0.05). Among females, the premature death probability declined from 6.71% to 4.90% (AAPC=-2.715%, P<0.05), whereas no statistically significant trend was observed in males (P>0.05). Life expectancy increased from 82.52 years in 2010 to 84.50 years in 2021, with an overall upward trend (AAPC=0.244%, P<0.05). Life expectancy rose by 1.71 years for males and 2.34 years for females (AAPC=0.197% and 0.303%,both P<0.05). Declines in premature death probability from malignant tumors (AAPC=-0.967%, P< 0.05) and chronic respiratory diseases (AAPC=-3.071%, P<0.05) contributed to gains in life expectancy of 0.30 years and 0.03 years, with contribution rates of 12.18% and 1.29%, respectively. Changes in premature death probability due to diabetes as well as cardiovascular and cerebrovascular diseases were not statistically significant (both P>0.05), resulting in reductions in life expectancy of 0.05 years and 0.10 years, with contribution rates of -2.40% and -5.05%, respectively. Notably, an increase in premature death probability due to cardiovascular and cerebrovascular diseases among males (AAPC=1.673%) contributed to a decrease of 0.22 years in male life expectancy, whereas a decrease among females (AAPC=-3.824%) contributed to an increase of 0.03 years in female life expectancy, with contribution rates of -13.03% and 1.14%, respectively. Conclusions From 2010 to 2021, Yangpu District experienced an overall decline in premature death probability due to four major chronic diseases and an increase in life expectancy. Greater attention should be paid to the negative impacts of premature death probability from diabetes as well as cardiovascular and cerebrovascular diseases among males on life expectancy.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged