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 Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.

The Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Objective : To explore the effect of dendrobium officinale polysaccharides(DOP) on necrotizing enterocolitis(NEC) in neonatal mice and to preliminarily explore the potential molecular mechanisms. Methods : Seven-day-old C57BL/6J mice were randomly divided into four groups: control(CTRL) group, necrotizing enterocolitis(NEC) group, low-dose DOP treatment(DOPL+NEC) group and high-dose DOP treatment(DOPH+NEC) group. The NEC model was established by hypoxia, cold stimulation, hypertonic feeding and intraperitoneal injection of lipopolysaccharide(LPS). At the end of the experiment, the small intestine tissues were collected. The general condition of the mice was observed, and body weight was recorded. Hematoxylin-eosin(HE) staining was used to observe pathological changes in the small intestine tissues. The expression levels of E-cadherin, Occludin and Claudin-1 were detected by immunohistochemistry and Western blot. The concentrations of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6 and IL-10 were measured by ELISA. The levels of lactate dehydrogenase(LDH), malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione(GSH) were detected using commercial kits. The expression levels of nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxygenase-1(HO-1) proteins were detected by immunohistochemistry and Western blot. Results : ompared with the CTRL group , the NEC group exhibited decreased body weight and increased HE pathological scores (P < 0. 01 or P < 0. 001) . The protein expression levels of E-cadherin , Occludin and Claudin-1 were reduced (P < 0. 01 or P < 0. 001) . The concentrations of TNF-α, IL-1βand IL-6 increased , while the concentration of IL-10 decreased (P < 0. 01) . The levels of MDA and LDH increased , while the levels of GSH and SOD decreased (P < 0. 01) . The protein expression levels of Nrf2 and HO-1 increased ( P < 0. 05 or P < 0. 01) . In contrast , DOP intervention groups showed increased body weight and decreased HE scores (P < 0. 05 or P < 0. 01) . The protein expression levels of E-cadherin , Occludin and Claudin-1 increased (P < 0. 05 or P < 0. 01 or P < 0. 01) . The concentrations of TNF-α, IL-1βand IL-6 decreased(P < 0. 05 or P < 0. 01 ) , while the concentration of IL-10 increased ( P < 0. 01) . The levels of MDA and LDH decreased , while the levels of GSH and SOD increased ( P < 0. 05 or P < 0. 01) . The protein expression levels of Nrf2 and HO-1 further increased (P < 0. 05 or P < 0. 01) . Conclusion DOP can ameliorate the pathological damage of necrotizing enterocolitis and enhance the intestinal mucosal barrier function in NEC mice . Additionally , it can also reduce oxidative stress injury and intestinal inflammation in NEC mice . The mechanism may be associated with the activation of the Nrf2/HO-1 pathway by DOP.

Objective:To investigate the effect of securinine(SEC)on apoptosis of the human colon cancer cell line SW620,and to elucidate its possible mechanism.Methods:The nude mice with subcutaneously transplanted tumor were divided into control group(n=6),oxaliplatin(OXA)group(n=7),and SEC group(n=7).The volume and mass of subcutaneous tumors in the nude mice were measured in various groups,and the tumor inhibitory rates in various groups were calculated.The SW620 cells were treated with different doses(5-120 μmol·L-1)of SEC for 12,24,48,and 72 h,respectively.Cell counting kit-8(CCK-8)assay was used to assess the survival rates of cells in various groups,and the optimal doses of SEC were confirmed.The SW620 cells were divided into control group,20 μmol·L-1 SEC group,40 μmol·L-1SEC group,and 40 μmol·L-1OXA group.TUNEL staining method and flow cytometry were used to detect the apoptotic rates of cells in various groups.JC-1 staining was used to detect the mitochondrial membrane potentials of cells in various groups,and 2',7'-dichlorodi-hydrofluorescin diacetate(DCFH-DA)fluorescence staining and flow cytometry were used to measure the reactive oxygen species(ROS)levels in the cells in various groups.Western blotting method was used to detect the expression levels of cytochrome C,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),mitogen-activated protein kinase p38,phosphorylated p38(p-p38),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)proteins in the cells in various groups.Results:Compared with control group,the volume and mass of subcutaneously transplanted tumors in the nude mice in SEC group were significantly decreased(P＜0.05 or P＜0.01 or P＜0.001);the inhibitory rates of tumor in SEC group and OXA group were 20.42％and 6.50％.The CCK-8 assay results showed that compared with 0 μmol·L-1 SEC,when the SEC dose exceeded 20 μmol·L-1,the survival rates of SW620 cells were significantly decreased(P＜0.001).The optimal condition for subsequent experiments was set as doses of 20 μmol·L-1SEC and 40 μmol·L-1SEC,and duration of 24 h.The TUNEL results showed that compared with control group,the apoptotic rates of cells in 20 and 40 μmol·L-1 SEC groups were significantly increased(P＜0.05 or P＜0.001).The results of flow cytometry showed that compared with control group,the apoptotic rate in 40 μmol·L-1SEC group was significantly increased(P＜0.001).The JC-1 staining results showed that compared with control group,the mitochondrial membrane potentials of cells in 20 and 40 μmol·L-1 SEC groups were significantly decreased(P＜0.001).Compared with control group,the levels of ROS detected by DCFH-DA fluorescence staining in the cells of 20 and 40 μmol·L-1 SEC groups and 40 μmol·L-1 OXA group were significantly increased(P＜0.001),while the level of ROS detected by flow cytometry in 40 μmol·L-1SEC group was significantly increased(P＜0.05).Compared with control group,the expression levels of Bcl-2 protein in the cells in 20 and 40 μmol·L-1 SEC groups and 40 μmol·L-1 OXA group were decreased(P＜0.01),while the expression levels of cytochrome C and Bax proteins were increased(P＜0.001).Compared with control group,the ratios of p-JNK/JNK,p-p38/p38 and p-ERK/ERK in 20 and 40 μmol·L-1 SEC groups were significantly increased(P＜0.05 or P＜0.01 or P＜0.001).Conclusion:SEC can inhibit the proliferation of SW620 cells,increase the cellular ROS levels,reduce the mitochondrial membrane potential,and induce the mitochondrial apoptosis;its mechanism may be related to the regulation of the mitogen-activated protein kinase(MAPK)signaling pathway.

OBJECTIVE To explore the expression,regulation,and downstream pathways of miR-21-5p in nasal type 2 inflammatory diseases.METHODS The expression levels of miR-21-5p were evaluated in nasal mucosa of patients with chronic rhinosinusitis with nasal polyps(CRSwNP)and healthy controls,as well as in nasal mucosa of CRSwNP and allergic rhinitis(AR)mouse models by real-time PCR.Human primary nasal epithelial cells were cultured and treated with different cytokines.The expression of miR-21-5p were then detected after 48 hours treatment.miR-21-5p lentivirus were used for overexpression in nasal epithelial cells.After 72 hours,cells were collected,and RNA was extracted for transcriptome analysis.Differentially expressed genes were further analyzed for pathway enrichment.RESULTS Compared with healthy controls,the expression of miR-21-5p was significantly increased in the nasal mucosa of CRSwNP patients(P<0.01).The expression of miR-21-5p was also significantly increased in mouse models of CRSwNP and AR respectively,compared to the control groups(P<0.01,respectively).The type 2 inflammation cytokines IL-4 and IL-13 can significantly upregulate miR-21-5p expression in nasal epithelial cells(P<0.01,respectively).Overexpression by lentivirus can significantly increase the expression of miR-21-5p in nasal epithelial cells,and lead to 118 differentially expressed genes.Those genes are significantly enriched in pathways associated with posttranscriptional gene silencing,WNT signaling and MAPKinase signaling.CONCLUSION miR-21-5p is upregulated in nasal type 2 inflammatory diseases partially controlled by IL-4 and IL-13.Overexpression of miR-21-5p lead to the changes of downstream pathways associated with WNT signaling and MAPKinase signaling in nasal epithelial cells.

The 2024 National Education Work Conference pointed out that at the current juncture of the critical period for achieving the goals and tasks of the 14th Five-Year Plan,the implementation of the Education Powerhouse Construction Plan Outline should be taken as the main line of work,and building first-class disciplines is an crucial task for a higher education powerhouse.In 2022,forensic medicine was officially listed as a first-level discipline under the medical category,presenting an un-precedented historical opportunity for the development of forensic medicine.The forensic medicine dis-cipline of Southern Medical University comprehensively improves the quality of talent cultivation and facilitates the construction of first-class disciplines as its main direction.It aims to initiate and imple-ment a high-level faculty team building plan featuring"combining recruitment and cultivation,inter-disciplinary integration";make vigorous efforts to establish a first-level doctoral program,refine advan-tageous second-level disciplines and research directions;and establish an innovative research platform from a high starting point with deep integration.The discipline adheres to moral cultivation and the Five Domains of Education simultaneous development,to build a high-quality talent joint training model.Guided by the construction of the national legal system and industry needs,the discipline will enhance social service capabilities.The forensic medicine construction in our university will continue to contribute to the rule of law in China and educational power.

Objective To investigate the characteristics and differences of congenital endowment in senile dementia population based on the theory of five circuits and six qi.Methods Based on the cross-sectional data of China Health and Retirement Longitudinal Survey(CHARLS)in 2018,the dementia status of the population aged 60 and above in China was evaluated by using the Mini-Mental State Examination(MMSE),and the five-circuit and six-qi features at birth in the senile dementia population were analyzed by descriptive statistics and Chi-square goodness-of-fit test.Results A total of 854 patients with senile dementia were included.The five-circuit and six-qi features at birth in the senile dementia population were as follows:most of them were born at the heavenly stem of Bing while the least at the heavenly stem of Ji and Geng(P＜0.001),most of them were born at the earthly branch of Wei while the least at the earthly branch of Zi(P＜0.001),most of them were born at the yearly circuit of excessive water circuit while the least at the yearly circuit of excessive gold circuit and deficient earth circuit(P＜0.001),and most of the patients were born at sitan of taiyin damp-earth and zaiquan of taiyang cold-water while the least at sitan of jueyin wind-wood and zaiquan of shaoyang ministerial fire;no statistically significant differences were found in the dominant qi and guest qi(P＞0.05);most of the patients were born in the year of combination of circuit and qi being Shunhua while the least in the year of combination of circuit and qi being same celestial correspondence(P＜0.001),and the patients born in the year of Shunhua usually were frequently distributed in heavenly-stem and earthly-branch year of Jiawu(P＜0.001).Conclusion There is a certain relationship between the congenital endowment at birth and the incidence of senile dementia in the population of senile dementia.The circuit-qi features at birth for the prevalence of senile dementia are the yearly circuit of excessive water circuit,sitan of taiyin damp-earth and zaiquan of taiyang cold-water,and the year of the combination of circuit and qi being Shunhua.The population born at the time with the above circuit-qi features are prone to suffer the injury of the kidneys,the heart,and the spleen,and then result into illness.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.