Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Objective: To analyze adverse event following immunization(AEFI) with the domestic bivalent human papilloma virus (HPV) vaccine among female students in primary, junior, and senior high schools in Hebei Province from 2022 to 2024, aiming to provide evidence for the vaccination program. Methods: On May 14, 2025, AEFI case data and vaccination data for the domestic bivalent HPV vaccine among female students in primary, junior, and senior high schools in Hebei Province from 2022 to 2024 were collected from the China Disease Control and Prevention Information System and the Hebei Provincial Immunization Program Information Management System, respectively. Statistical analysis was performed by using descriptive and analytical epidemiological methods, with intergroup comparisons conducted by using the Chi square test or Fisher s exact probability test. Results: From 2022 to 2024, a total of 817 900 doses of the domestic bivalent HPV vaccine were administered to female students in primary, junior, and senior high schools in Hebei Province. A total of 68 AEFI cases were reported, comprising 57 common vaccine reactions, 7 rare vaccine reactions, 3 coincidental events, and 1 psychogenic reaction. The overall AEFI reporting rate was 8.31 per 100 000 doses, 4 cases (2.30/100 000 doses), 31 cases (8.73/100 000 doses), and 33 cases (11.41/100 000 doses) were reported in 2022, 2023, and 2024, respectively, with a statistically significant difference across years ( χ 2=10.97, P <0.01). The reporting rates for common and rare vaccine reactions were 6.97 per 100 000 doses and 0.86 per 100 000 doses, respectively. The AEFI reporting rates were 15.14 per 100 000 doses among primary school girls and 8.20 per 100 000 doses among secondary school girls, though the difference was not statistically significant (Fisher s exact test, P =0.30). The reporting rate was higher after the first dose (10.91/100 000 doses) than after the second dose (5.96/100 000 doses; χ 2=5.85, P =0.02).The second quarter recorded the highest AEFI reporting rate at 11.21 per 100 000 doses. The majority of AEFI cases (56 cases, 82.35%) occurred within 24 hours post vaccination. Conclusion The domestic bivalent HPV vaccine demonstrates a favorable safety profile among female students in Hebei Province, with a low overall AEFI reporting rate that consisted predominantly of general reactions and occasional cardiac related reactions.

ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan （DSS） in ameliorating renal injury in db/db mice. MethodsThirty 8-week-old specific pathogen-free （SPF）-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L^-1. The 30 db/db mice were randomly divided into five groups： the model group， the irbesartan （IBN） group， and three DSS dose groups （low-， medium-， and high-dose DSS groups， administered at 16.77， 33.54， 67.08 g·kg^-1·d^-1， respectively）. Additionally， the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg^-1·d^-1 by gavage， while the three DSS groups received DSS at 16.77， 33.54， and 67.08 g·kg^-1·d^-1 by gavage， respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention， serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary total protein （UTP）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of silencing information regulator 1 （SIRT1）， hypoxia-inducible factor-1α （HIF-1α）， very low-density lipoprotein receptor （VLDLr）， and cluster of differentiation 31 （CD31）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3. ResultsCompared to the normal group， the model group showed significantly increased SCr， BUN， UTP， TG， and LDL-C. HE staining revealed glomerulosclerosis， mesangial matrix hyperplasia， capillary loop distortion and thickening， with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels increased （P<0.05）. Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 （P<0.05）， indicating hypoxia and apoptosis in renal cells. In all treatment groups， SCr， BUN， TG， and LDL-C were significantly reduced compared to the model group （P<0.05）， and UTP was significantly improved in the medium-dose DSS group （P<0.05）. Renal tissue structure and morphology were improved， inflammatory cells were reduced， and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels decreased （P<0.05）. Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups （P<0.05）， with the most significant improvement observed in the IBN group and medium-dose DSS group （P<0.05）. ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice， and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.

ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg^-1·d^-1）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers. ResultsCompared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

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.

ObjectiveTo investigate the independent predictive factors for 90-day mortality in patients with acute-on-chronic liver failure （ACLF）， to establish a risk predictive model， and to assess its predictive efficacy in comparison with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ. MethodsA retrospective analysis was performed for the clinical data of 394 patients with ACLF who were admitted to The Affiliated Hospital of Inner Mongolia Medical University and Hohhot Second Hospital from July 2018 to July 2024， and general information and laboratory markers on admission were collected from all patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of quantitative data between two groups， and the chi-square test or the adjusted chi-square test was used for comparison of qualitative data between two groups. The LASSO regression analysis was used to identify related variables， and the multivariate logistic regression analysis was used to establish a predictive model and generate a nomogram. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， calibration curve， and clinical decision curve were used to assess the performance of the model. ResultsA total of 394 patients with ACLF were included in this study， with 136 patients in the training set， 58 in the internal validation set， and 200 in the external validation set. The cohort had a mean age of 52.9±11.7 years， among whom male patients accounted for 72.84% （287/394）， the patients with HBV infection accounted for 22.33% （88/394）， the patients with alcohol-related causes accounted for 45.94% （181/394）， and the patients with other causes （including drug-induced and autoimmune diseases） accounted for 31.73% （125/394）. The overall 90-day mortality rate was 27.41% （108/394）. The multivariate logistic regression analysis showed that diabetes （odds ratio ［OR］= 5.831， 95% confidence interval ［CI］： 1.587 — 21.424， P=0.008）， cystatin C （Cys-C） （OR=2.984， 95%CI： 1.501 — 5.933， P=0.002）， and spontaneous peritonitis （SBP） （OR=5.692， 95%CI： 2.150 — 15.071， P<0.001） were independent risk factors， and a nomogram was generated based on these factors. This model had an AUC of 0.836 in the training set， 0.881 in the internal validation set， and 0.878 in the external validation set， showing a good discriminatory ability. The calibration curve showed a good degree of fitting， with a relatively high net clinical benefit. The subgroup analysis based on etiology showed that the model had an AUC of 0.850 in the patients with HBV infection， 0.858 in the patients with alcohol-induced ACLF， and 0.908 in the patients with other etiologies， indicating that the model had a good discriminatory ability across the populations with different etiologies. Compared with traditional scores， the model （AUC=0.836） had a significantly better predictive value than MELD （AUC=0.619， Z=3.197， P=0.001）， MELD-Na （AUC=0.651， Z=2.998， P=0.003）， MELD 3.0 （AUC=0.601， Z=3.682， P<0.001）， and COSSH-ACLF Ⅱ （AUC=0.719， Z=2.396， P=0.017） alone. ConclusionDiabetes， SBP， and Cys-C are independent risk factors for 90-day mortality in patients with ACLF. Compared with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ scores， this model has a higher predictive value for 90-day prognosis in patients with ACLF and is suitable for patients with ACLF caused by various etiologies.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

ObjectiveTo investigate the effectiveness of teaching pedagogy based on outcome-based education (OBE) and conceive-design-implement-operate (CDIO) model in the teaching of exercise rehabilitation training. MethodsTwenty-seven postgraduate students majoring in exercise rehabilitation training of grade 2024 at Capital University of Physical Education and Sports were randomly divided into control group (n = 13) and experimental group (n = 14). The control group received routine teaching methods, while the experimental group received teaching of OBE-CDIO. After the course, theoretical scores, objective structured clinical examination (OSCE) scores and teaching satisfaction via questionnaire were compared between two groups. ResultsAfter the course, there was no significant difference in theoretical scores between two groups (t = 1.103, P > 0.05). Scores in all stations of OSCE were higher in the experimental group than in the control group (t > 2.181, P < 0.05), as well as the satisfaction scores of learning, enthusiasm, organization, group interaction, individual affinity, workload and examination (|t| > 3.781, P < 0.001). ConclusionThe teaching pedagogy based on the OBE-CDIO model can improve practical competence and teaching satisfaction among postgraduate students majoring in exercise rehabilitation training.

ObjectiveTo explore the training path of rehabilitation therapy professionals in local colleges and universities under the background of New Medicine. MethodsTaking Jining Medical University as an example, combining the interdisciplinary integration, intelligent driving and people-oriented New Medicine attributes of rehabilitation therapy, this study focused on the current practical problems in rehabilitation education, accurately aligned with the requirements of new medicine construction, reshaped the curriculum system with new concepts, empowered practical innovation with new technologies, and cultivated humanistic literacy with new connotations. By deeply integrating digital construction with educational practice, it carried out the construction and practice of the New Medicine talent training model in rehabilitation therapy, helping students form a stereoscopic knowledge structure, possess the ability to apply intelligent rehabilitation technology and solve complex rehabilitation problems, and become high-quality rehabilitation therapy talents with both morality and ability. ResultsThe overall construction of the rehabilitation therapy major established a model of Dual fusion foundation, Three element empowerment and Three dimensional soul casting, including reform and innovation in curriculum system, practical mode and moral education mechanism. It has formed a health oriented "vertical and horizontal integration-discipline fusion" dual-fusion stereoscopic curriculum system, an intelligent led "theory and practice-science and education-industry and education" three element integration practical mode, and a confucian medical culture "curriculum-practice-evaluation" three-dimensional integrated moral education mechanism. Through practical testing, this model achieved significant results and was widely recognized, including a significant improvement in the quality of talent cultivation, prominent achievements in resource construction, and prominent achievements in health services, providing strong support for the construction of regional rehabilitation medical systems. ConclusionThe reform of the rehabilitation treatment talent training model at Jining Medical University under the background of New Medicine provides a replicable and promotable practical paradigm for the training of rehabilitation talents in similar universities through reshaping the curriculum system, strengthening practical innovation, and cultivating humanistic literacy.

ObjectiveTo investigate the effectiveness of teaching pedagogy based on outcome-based education (OBE) and conceive-design-implement-operate (CDIO) model in the teaching of exercise rehabilitation training. MethodsTwenty-seven postgraduate students majoring in exercise rehabilitation training of grade 2024 at Capital University of Physical Education and Sports were randomly divided into control group (n = 13) and experimental group (n = 14). The control group received routine teaching methods, while the experimental group received teaching of OBE-CDIO. After the course, theoretical scores, objective structured clinical examination (OSCE) scores and teaching satisfaction via questionnaire were compared between two groups. ResultsAfter the course, there was no significant difference in theoretical scores between two groups (t = 1.103, P > 0.05). Scores in all stations of OSCE were higher in the experimental group than in the control group (t > 2.181, P < 0.05), as well as the satisfaction scores of learning, enthusiasm, organization, group interaction, individual affinity, workload and examination (|t| > 3.781, P < 0.001). ConclusionThe teaching pedagogy based on the OBE-CDIO model can improve practical competence and teaching satisfaction among postgraduate students majoring in exercise rehabilitation training.