AIM:To observe the effects of Huazhuo granules on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/glycogen synthase kinase-3β(GSK-3β)and PI3K/Akt/forkhead box protein O1(FOXO1)signaling pathways in the liver tissue of type 2 diabetes mellitus(T2DM)rats,and to explore its mechanism of action in regulating glycogen synthesis and gluconeogenesis.METHODS:Thirty 8-week-old SPF-grade male SD rats were chosen,with 5 ran-domly selected ones as the blank control group.The remaining 25 rats were fed to a high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin to establish a T2DM rat model.After successful mod-eling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with met-formin,and low,medium,and high-dose Huazhuo granule groups,resulting in a total of 6 groups with 5 rats in each.Rats in the treatment groups were gavaged with the corresponding doses of medication,while those in the blank control and model groups were gavaged with an equal volume of saline once daily for 4 consecutive weeks.After 24-hour fasting with free access to water,the rats were euthanized to measure blood glucose,serum insulin levels,and serum triglyceride(TG),total cholesterol(T-CHO),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels.Liver pathological morphology was assessed by hematoxylin-eosin staining,and liver glycogen storage was detected by periodic acid-Schiff staining.Immunohistochemistry and Western blot analysis were employed to detect the protein levels of p-PI3K,p-Akt,p-FOXO1 and p-GSK-3β in the liver of rats in each group.The mRNA levels of phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6Pase),GSK-3β,FOXO1,PI3K and Akt in liver tissues were detected by RT-qPCR.RESULTS:Compared with the model group,the rats in the high-dose Huazhuo Granule group and the metformin group exhibited decreased blood glucose and insulin levels(P<0.01),reduced AST,ALT,TG,and T-CHO concentrations(P<0.01),and increased HDL-C concentrations(P<0.01).The phosphorylation levels of PI3K,Akt,FOXO1,and GSK-3β proteins were up-regulated(P<0.01).In con-trast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3β were all down-regulated(P<0.01).Conversely,the gene expressions of PI3K and Akt were upregulated(P<0.01).Pathological morphology of the liver tissue improved,accompanied by increased glycogen deposition in hepatocytes.CONCLUSION:Huazhuo granule manifests effects in lowering blood glucose and serum insulin levels,ameliorating blood lipids,and enhancing liver function in rats.These ef-fects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3β signaling pathway and reduce gluco-neogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.

As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.

Objective:To investigate the value of anlotinib combined with radiotherapy in second-line targeted drug-resistant advanced lung adenocarcinoma with epidermal growth factor receptor(EGFR) mutation.Methods:A total of 150 patients with advanced lung adenocarcinoma with EGFR mutation who were resistant to second-line targeted therapy and admitted to the Affiliated Hospital of Shaoxing University from July 2021 to July 2023 were prospectively selected as the study objects, and they were divided into the control group and the study group by random number table method, with 75 cases in each group. The control group received radiotherapy, and the study group received anrotinib combined radiotherapy. The recent clinical effects, tumor indexes, cellular immune indexes and the occurrence of adverse reactions were compared between the two groups.Results:After treatment, the objective response rate (ORR) and disease control rate (DCR) in the study group were higher than those in the control group: 53.33%(40/75) vs. 34.67%(26/75), 86.67%(65/75) vs. 64.00%(48/75), there were statistical differences ( χ2 = 5.30, 10.37, P<0.05). After treatment, the levels of VEGF, cytokeratin 21-1 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in the study group were lower than those in the control group: (472.93 ± 45.71) ng/L vs. (510.26 ± 50.49) ng/L, (4.82 ± 1.13) μg/L vs. (5.25 ± 1.34) μg/L, (5.65 ± 1.24) μg/L vs. (6.17 ± 1.42) μg/L, there were statistical differences ( P<0.05). After treatment, the levels of CD 3+, CD 4+ and CD 4+/CD 8+ in the study group were higher than those in the control group, and the level of CD 8+ was lower than that in the control group: 0.532 ± 0.044 vs. 0.508 ± 0.041, 0.321 ± 0.030 vs. 0.305 ± 0.027, 1.02 ± 0.19 vs. 0.93 ± 0.16, 0.303 ± 0.040 vs. 0.320 ± 0.044, there were statistical differences ( P<0.05). There was no significant difference in the occurrence of adverse reactions between the two groups ( P>0.05). Conclusions:Anlotinib combined with radiotherapy can enhance the clinical efficacy of second-line targeted drug resistant advanced lung adenocarcinoma with EGFR mutation, improve tumor indexes, promote the recovery of immune function, without significantly increasing adverse reactions.

Objective:To investigate the effects of the expanded lateral thoracic artery perforator flap in the reconstruction of breast scar contracture deformity after burns in minor females.Methods:The study was a retrospective observational study. From July 2018 to October 2023, 8 female children aged 4 to 12 years and with breast scar contracture deformity after burns, who met the inclusion criteria, were admitted to the Department of Burns and Plastic Surgery of Guangzhou Red Cross Hospital of Jinan University. The skin and soft tissue expander (hereinafter referred to as expander) was placed in the first stage. The contracture scar was removed and released in the second stage, and the wound formed after the scar was removed measured between 9 cm×8 cm and 15 cm×10 cm. The expanded lateral thoracic artery perforator flap was designed and transferred to repair the wound with resected flap area of 10 cm×9 cm to 16 cm×11 cm, and the wound at the flap donor area was directly sutured. The complications such as incision infection, hematoma, and expander exposure were observed after stage Ⅰ surgery. After stage Ⅱ surgery, the survival of the flap and the wound healing at the flap donor area were observed. During the 1-year follow-up after the stage Ⅱ surgery, the breast development was evaluated according to tanner staging performance of female pubertal breast development, the aesthetic effect of the affected breast was evaluated by using the aesthetic effect evaluation standard after breast surgery, the Vancouver scar scale (VSS) was used to score the scar condition at the flap donor and recipient areas, and the satisfaction of the children's families with the surgical outcomes was investigated by using a self-made scale.Results:After stage Ⅰ surgery, no incision infection, hematoma, expander exposure, or other complications occurred in 8 children. After stage Ⅱ surgery, only one child had tissue necrosis at the distal end of the flap with a size of about 2 cm×1 cm, which healed after dressing change, and the flap in other children had good blood supply, soft texture, moderate thickness, and similar color to the skin at the recipient area. The wounds at all flap donor areas healed well. During the 1-year follow-up after stage Ⅱ surgery, 7 children had normal breast development, with their breast volume, height, and shape being almost the same as or similar to the healthy side, with the aesthetic effect of all being grade Ⅰ; the breast in one child had not yet developed, and these indicators were not evaluated. The locations of nipple areola complex in 8 children were almost the same as or similar to those in the healthy side, and their skin color, integrity, texture, and elasticity of the partial breast repaired by the transferred flap were similar to those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The shapes of nipple and areola in 5 children were inconsistent with those in the healthy side because of the original scar, with the aesthetic effect of all being grade Ⅱ, and the shapes of nipple and areola in the other 3 children were consistent with those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The VSS score of the scar at the flap recipient area was 2-5, and the VSS score of the scar at the flap donor area was 1-3. Seven children's families were satisfied with the surgical effect, and one child's family was basically satisfied with the surgical effect.Conclusions:For the breast scar contracture deformity of minor females after burns, the expanded lateral thoracic artery perforator flap is used for reconstruction before puberty, which results in fewer postoperative complications, good breast shape, and hidden scar at the flap donor area. It is beneficial for the normal development of adolescent breasts, and is one of the safe and effective methods for the treatment of breast scar contracture deformity in minor females after burns.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

Ferroptosis, a newly discovered form of iron-dependent regulation of cell death, has been found to be associated with the development of various cancers, including melanoma. This review summarizes recent progress in roles of ferroptosis in the pathogenesis, metastasis and treatment of melanoma, aiming to provide a theoretical basis for the development of new drugs and new treatment strategies for melanoma in clinical practice.

Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.

As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.

AIM:To observe the effects of Huazhuo granules on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/glycogen synthase kinase-3β(GSK-3β)and PI3K/Akt/forkhead box protein O1(FOXO1)signaling pathways in the liver tissue of type 2 diabetes mellitus(T2DM)rats,and to explore its mechanism of action in regulating glycogen synthesis and gluconeogenesis.METHODS:Thirty 8-week-old SPF-grade male SD rats were chosen,with 5 ran-domly selected ones as the blank control group.The remaining 25 rats were fed to a high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin to establish a T2DM rat model.After successful mod-eling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with met-formin,and low,medium,and high-dose Huazhuo granule groups,resulting in a total of 6 groups with 5 rats in each.Rats in the treatment groups were gavaged with the corresponding doses of medication,while those in the blank control and model groups were gavaged with an equal volume of saline once daily for 4 consecutive weeks.After 24-hour fasting with free access to water,the rats were euthanized to measure blood glucose,serum insulin levels,and serum triglyceride(TG),total cholesterol(T-CHO),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels.Liver pathological morphology was assessed by hematoxylin-eosin staining,and liver glycogen storage was detected by periodic acid-Schiff staining.Immunohistochemistry and Western blot analysis were employed to detect the protein levels of p-PI3K,p-Akt,p-FOXO1 and p-GSK-3β in the liver of rats in each group.The mRNA levels of phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6Pase),GSK-3β,FOXO1,PI3K and Akt in liver tissues were detected by RT-qPCR.RESULTS:Compared with the model group,the rats in the high-dose Huazhuo Granule group and the metformin group exhibited decreased blood glucose and insulin levels(P<0.01),reduced AST,ALT,TG,and T-CHO concentrations(P<0.01),and increased HDL-C concentrations(P<0.01).The phosphorylation levels of PI3K,Akt,FOXO1,and GSK-3β proteins were up-regulated(P<0.01).In con-trast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3β were all down-regulated(P<0.01).Conversely,the gene expressions of PI3K and Akt were upregulated(P<0.01).Pathological morphology of the liver tissue improved,accompanied by increased glycogen deposition in hepatocytes.CONCLUSION:Huazhuo granule manifests effects in lowering blood glucose and serum insulin levels,ameliorating blood lipids,and enhancing liver function in rats.These ef-fects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3β signaling pathway and reduce gluco-neogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.