Objective To investigate the ameliorative effect of Qihuakeli,a Hani formula,on glycolipid metabolism in type 2 diabetes mellitus by in vivo and in vitro experiments.Methods Rat liver mesenchymal stromal cells(BRL-3A)were inoculated in six-well plates and divided into blank,palmitic acid,fenofibrate,and Qihuakeli serum-containing 5.4,10.8,and 21.6 g/kg groups.Except for the blank group,the remaining groups were intervened with 0.2 mmol/L palmitic acid(PA)for 24 hour,and then added with drug-containing serum,and then continued to incubate for 24 hour.The proliferation rate of BRL-3A cells in each group was determined.Total cholesterol(T-CHO),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)concentrations in the supernatant of each cell group were measured,cell culture medium was aspirated and discarded,triglyceride(TG)concentration in the cell lysate.The lipid content of the cells was determined by measuring and staining with red oil.Meanwhile,45 rats were taken and divided into blank group,model group,fenofibrate group(0.225 g/kg),Qihuakeli compound 5.4 g/kg group,and Qihuakeli compound 10.8 g/kg group,the blank group was given normal feed and the rest of the groups were given high-fat feed for 42 day.Beginning on the 43rd day,each group,except the blank group,was injected with a single intraperitoneal injection of Starting from the 43rd day,except the blank group,each group was given a one-time intraperitoneal injection of 0.25%streptozotocin(STZ)solution,and at the same time,the corresponding drugs were given by gavage for 14 day.The rats'weight gain and liver index were measured.Serum fasting blood glucose(FBG)and fasting insulin(FINS)were detected,and the insulin resistance index(ISI)was calculated.Serum free fatty acid(FFA)levels and tumor necrosis factor-α(TNF-α)in liver tissue were also detected.HE staining was used to detect pathological changes in the pancreas.Pathological changes were observed in the tissues,and islet α and β cell expression was detected by immunohistochemistry.Results Compared to the PA group,the accumulation rate of BRL-3A cells was significantly higher(P<0.01)in the 10.8 and 21.6 g/kg Qihuakeli-containing serum groups.The levels of T-CHO,LDL-C and TG in the 5.4 and 21.6 g/kg serum groups were significantly lower(P<0.05),and HDL-C levels significantly increased(P<0.05).Oil red staining results showed that lipids in the cytoplasm of the 5.4,10.8 and 21.6 g/kg.Qihuacel-containing groups significantly reduced.Compared to the model group,the body weight of the 10.8 g/kg group containing Qihuakeli granules increased significantly(P<0.05).The liver index of the 5.4 g/kg group containing Qihuakeli decreased significantly(P<0.05).The serum indices of FBG,FINS,FFA and insulin resistance of the 5 g/kg group containing Qihuakeli decreased significantly(P<0.05).In the 5.4,10.8 g/kg groups,all serum FBG,FINS,FFA and insulin resistance indices significantly reduced in the 5.4 and 10.8 g/kg Qihuakeli groups(P<0.05 or P<0.01).TNF-α levels were significantly reduced(P<0.01).HE staining showed that a small number of lymphocytes were scattered in the pancreatic ducts and perivascular area of the rats in the Qihuakeli 5.4 and 10.8 g/kg groups,the local vasodilatation was observed,the number of pancreatic islet cells and the area of islet cells significantly increased.Immunohistochemical study was further used.The results of immunohistochemistry showed that the area of pancreatic islet α-cells significantly reduced and the area of pancreatic islet β-cells significantly increased in Qihuakeli 5.4 and 10.8 g/kg groups.Conclusion Qihuakeli compound improved glucose-lipid metabolism in T2DM,probably by improving the function of pancreatic islet cells,increasing the sensitivity of insulin to blood glucose,improving insulin resistance,decreasing the secretion of insulin and glucagon,and thus lowering the level of fasting blood glucose.Meanwhile,by decreasing the content of TNF-α,inhibiting lipolysis in the body,and promoting the uptake of FFA by adipocytes,and further lowering the FFA.Thus,it regulates the levels of TG,T-CHO,HDL-C and LDL-C,improves the abnormalities of glucose and lipid metabolism,and alleviates T2DM.

Infertility is a common reproductive disorder affecting millions of couples worldwide. It is estimated that male factors account for about 30%-50% of infertility cases, and some studies have found that the concentration of male sperm gradually decreases over time, a trend that suggests the importance of male fertility. Many factors contribute to the decline of male fertility, among which environmental factors have received widespread attention. After reaching adulthood, spermatogonial stem cells will continue to produce sperm, but these cells exist outside the blood testicular barrier, which makes them highly sensitive to environmental conditions such as air pollution, tobacco smoke, radiation, and heavy metals. It is reported that exposure to these adverse environmental factors not only causes oxidative stress and DNA damage to germ cells, but also leads to abnormal epigenetic modification of sperm DNA, thereby causing a series of diseases. This article reviewed the abnormal methylation changes in DNA associated with exposure to environmental pollutants during spermatogenesis and how these changes affect the quantity, quality, and function of spermatozoa.

Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

Objective To explore the risk factors for recurrent laryngeal nerve(RLN)invasion in patients with papillary thyroid carcinoma(PTC)based on ultrasound image characteristics,construct a regression equation,and explore its predictive value for providing a reference for the clinical prevention and treatment of RLN invasion in PTC patients.Methods A retrospective analysis was conducted on 1 195 patients who were pathologically diagnosed with PTC in the Affiliated TCM Hospital of Guangzhou Medical University and Nanfang Hospital,Southern Medical University from January 2020 to November 2024.These patients were divided into invasion group(n=28)and non-invasion group(n=1167)according to whether they had RLN invasion or not.The clinical data,pathological data and ultrasound image characteristics were compared between two groups.The risk factors for RLN invasion in PTC patients were identified using multifactorial Logistic regression to construct a regression equation which was then evaluated using the likelihood ratioχ2.Moreover,the Hosmer-Lemeshow test was utilized to assess the goodness of fit,and the receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of the regression equation for RLN invasion in PTC patients,and the area under the curve(AUC)was calculated.Results The proportions of patients with tumor located in the posterior sagittal position,maximum tumor diameter≥1 cm,capsule contact and lymph node metastasis were higher in invasion group than in non-invasion group(P<0.05).Multifactorial Logistic regression analysis identified tumor located in the posterior sagittal position(OR=1.079,95%CI:1.031-1.129),maximum tumor diameter≥1 cm(OR=2.408,95%CI:1.256-4.617),capsule contact(OR=3.171,95%CI:1.724-5.833),and lymph node metastasis(OR=3.425,95%CI:1.884-6.226)as independent risk factors for RLN invasion in PTC patients(P<0.05).The regression equation was constructed as followed:logit(P)=-8.552+tumor located in the posterior sagittal position×0.076+maximum tumor diameter≥1 cm×0.879+capsule contact×1.154+lymph node metastasis×1.231.The likelihood ratioχ2 evaluation of the regression equation suggested that the regression equation was effectively constructed(P<0.001).Hosmer-Lemeshow test for the goodness of fit of the regression equation showed that the regression equation was well fitted(P>0.05).ROC curve analysis revealed that when logit(P)>0.875,the AUC value was 0.901(95%CI:0.882-0.917),with a sensitivity of 75.00%and a specificity of 88.95%.Conclusion The occurrence of RLN invasion in PTC patients is associated with tumor located in the posterior sagittal position,maximum tumor diameter≥1 cm,capsule contact,and lymph node metastasis,and the regression equations constructed based on these factors can well predict the occurrence of RLN invasion in PTC patients and is expected to provide an effective guidance for clinical practice.

Objective To investigate the ameliorative effect of Qihuakeli,a Hani formula,on glycolipid metabolism in type 2 diabetes mellitus by in vivo and in vitro experiments.Methods Rat liver mesenchymal stromal cells(BRL-3A)were inoculated in six-well plates and divided into blank,palmitic acid,fenofibrate,and Qihuakeli serum-containing 5.4,10.8,and 21.6 g/kg groups.Except for the blank group,the remaining groups were intervened with 0.2 mmol/L palmitic acid(PA)for 24 hour,and then added with drug-containing serum,and then continued to incubate for 24 hour.The proliferation rate of BRL-3A cells in each group was determined.Total cholesterol(T-CHO),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)concentrations in the supernatant of each cell group were measured,cell culture medium was aspirated and discarded,triglyceride(TG)concentration in the cell lysate.The lipid content of the cells was determined by measuring and staining with red oil.Meanwhile,45 rats were taken and divided into blank group,model group,fenofibrate group(0.225 g/kg),Qihuakeli compound 5.4 g/kg group,and Qihuakeli compound 10.8 g/kg group,the blank group was given normal feed and the rest of the groups were given high-fat feed for 42 day.Beginning on the 43rd day,each group,except the blank group,was injected with a single intraperitoneal injection of Starting from the 43rd day,except the blank group,each group was given a one-time intraperitoneal injection of 0.25%streptozotocin(STZ)solution,and at the same time,the corresponding drugs were given by gavage for 14 day.The rats'weight gain and liver index were measured.Serum fasting blood glucose(FBG)and fasting insulin(FINS)were detected,and the insulin resistance index(ISI)was calculated.Serum free fatty acid(FFA)levels and tumor necrosis factor-α(TNF-α)in liver tissue were also detected.HE staining was used to detect pathological changes in the pancreas.Pathological changes were observed in the tissues,and islet α and β cell expression was detected by immunohistochemistry.Results Compared to the PA group,the accumulation rate of BRL-3A cells was significantly higher(P<0.01)in the 10.8 and 21.6 g/kg Qihuakeli-containing serum groups.The levels of T-CHO,LDL-C and TG in the 5.4 and 21.6 g/kg serum groups were significantly lower(P<0.05),and HDL-C levels significantly increased(P<0.05).Oil red staining results showed that lipids in the cytoplasm of the 5.4,10.8 and 21.6 g/kg.Qihuacel-containing groups significantly reduced.Compared to the model group,the body weight of the 10.8 g/kg group containing Qihuakeli granules increased significantly(P<0.05).The liver index of the 5.4 g/kg group containing Qihuakeli decreased significantly(P<0.05).The serum indices of FBG,FINS,FFA and insulin resistance of the 5 g/kg group containing Qihuakeli decreased significantly(P<0.05).In the 5.4,10.8 g/kg groups,all serum FBG,FINS,FFA and insulin resistance indices significantly reduced in the 5.4 and 10.8 g/kg Qihuakeli groups(P<0.05 or P<0.01).TNF-α levels were significantly reduced(P<0.01).HE staining showed that a small number of lymphocytes were scattered in the pancreatic ducts and perivascular area of the rats in the Qihuakeli 5.4 and 10.8 g/kg groups,the local vasodilatation was observed,the number of pancreatic islet cells and the area of islet cells significantly increased.Immunohistochemical study was further used.The results of immunohistochemistry showed that the area of pancreatic islet α-cells significantly reduced and the area of pancreatic islet β-cells significantly increased in Qihuakeli 5.4 and 10.8 g/kg groups.Conclusion Qihuakeli compound improved glucose-lipid metabolism in T2DM,probably by improving the function of pancreatic islet cells,increasing the sensitivity of insulin to blood glucose,improving insulin resistance,decreasing the secretion of insulin and glucagon,and thus lowering the level of fasting blood glucose.Meanwhile,by decreasing the content of TNF-α,inhibiting lipolysis in the body,and promoting the uptake of FFA by adipocytes,and further lowering the FFA.Thus,it regulates the levels of TG,T-CHO,HDL-C and LDL-C,improves the abnormalities of glucose and lipid metabolism,and alleviates T2DM.

Objective To explore the risk factors for recurrent laryngeal nerve(RLN)invasion in patients with papillary thyroid carcinoma(PTC)based on ultrasound image characteristics,construct a regression equation,and explore its predictive value for providing a reference for the clinical prevention and treatment of RLN invasion in PTC patients.Methods A retrospective analysis was conducted on 1 195 patients who were pathologically diagnosed with PTC in the Affiliated TCM Hospital of Guangzhou Medical University and Nanfang Hospital,Southern Medical University from January 2020 to November 2024.These patients were divided into invasion group(n=28)and non-invasion group(n=1167)according to whether they had RLN invasion or not.The clinical data,pathological data and ultrasound image characteristics were compared between two groups.The risk factors for RLN invasion in PTC patients were identified using multifactorial Logistic regression to construct a regression equation which was then evaluated using the likelihood ratioχ2.Moreover,the Hosmer-Lemeshow test was utilized to assess the goodness of fit,and the receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of the regression equation for RLN invasion in PTC patients,and the area under the curve(AUC)was calculated.Results The proportions of patients with tumor located in the posterior sagittal position,maximum tumor diameter≥1 cm,capsule contact and lymph node metastasis were higher in invasion group than in non-invasion group(P<0.05).Multifactorial Logistic regression analysis identified tumor located in the posterior sagittal position(OR=1.079,95%CI:1.031-1.129),maximum tumor diameter≥1 cm(OR=2.408,95%CI:1.256-4.617),capsule contact(OR=3.171,95%CI:1.724-5.833),and lymph node metastasis(OR=3.425,95%CI:1.884-6.226)as independent risk factors for RLN invasion in PTC patients(P<0.05).The regression equation was constructed as followed:logit(P)=-8.552+tumor located in the posterior sagittal position×0.076+maximum tumor diameter≥1 cm×0.879+capsule contact×1.154+lymph node metastasis×1.231.The likelihood ratioχ2 evaluation of the regression equation suggested that the regression equation was effectively constructed(P<0.001).Hosmer-Lemeshow test for the goodness of fit of the regression equation showed that the regression equation was well fitted(P>0.05).ROC curve analysis revealed that when logit(P)>0.875,the AUC value was 0.901(95%CI:0.882-0.917),with a sensitivity of 75.00%and a specificity of 88.95%.Conclusion The occurrence of RLN invasion in PTC patients is associated with tumor located in the posterior sagittal position,maximum tumor diameter≥1 cm,capsule contact,and lymph node metastasis,and the regression equations constructed based on these factors can well predict the occurrence of RLN invasion in PTC patients and is expected to provide an effective guidance for clinical practice.

Objective To investigate the pharmacological effects of"Yajieshaba"on mice with alcohol-induced liver injury and to investigate the mechanism of the impact of"Yajieshaba"on the regulation of intestinal flora by 16S rDNA technology.Methods Healthy male KM mice were randomly divided into control,model,"Yajieshaba"low,medium,and high dose(0.39,1.17 and 3.51 g·kg-1)groups and Bifendatatum(2.93 mg·kg-1)groups,with eight mice in each group.After one week of pre-administration of"Yajieshaba",a mouse model of acute alcoholic liver injury was established by a single instillation of 56%alcohol,and the levels of AST and ALT in the serum of mice were measured,and the morphological changes of liver histology were observed by HE staining;secondly,faecal DNA was extracted from each group under aseptic operation,and 16S rDNA sequencing and differential analysis by alpha diversity and species composition at the phylum and genus levels were performed.Results The results showed that the biochemical indexes of liver function(ALT and AST)were significantly improved by"Yajieshaba",and the degree of liver damage was significantly reduced by HE staining.At the phylum level,it significantly decreased the abundance of Aspergillus and increased the quantity of Bacteroides;at the genus level,it significantly up-regulated the plenty of Bacteroides and Prevotella and downregulated a lot of Prevotella and Helicobacter.At the genus level,"Yajieshaba"significantly up-regulated the abundance of Bacillus spp.and Prevotella spp.and down-regulated the abundance of Prevotella spp.and Helicobacter spp.Conclusion"Yajieshaba"may play an anti-acute alcoholic liver injury effect by regulating the intestinal flora and metabolites.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

AIM: To explore the effect of ethanol extract of costusroot (EEC) on gastric mucosa in gastric ulcer rats and related mechanism. METHODS: The rats were randomly divided into 5 groups: normal group, model group, sucralfate group, low-EEC group and high-EEC group, and anhydrous alcohol was administrated intragastrically to replicate gastric ulcer model in groups other than the normal. Changes in the area of gastric ulcer were observed and the inhibition rate of ulcer was calculated. The pathological changes of gastric tissue were measured by HE staining, and the protein expression levels of Bax and Bcl-2 were tested by immunohistochemistry and Western blot. RESULTS: EEC inhibited the formation of ulcer area in model rats and alleviated the histopathological damage to the stomach caused by ethanol. While enhancing the expression of Bcl-2 protein (P<0.01), it effectively inhibited the overexpression of Bax (P<0.01). CONCLUSION: EEC has a strong function of anti-gastric ulcers, and its mechanism of action might be related to the regulation of the protein expression level of Bax and Bcl-2 to inhibit the apoptosis of gastri mucosal cells.

Objective To study the giant invasive pituitary tumor neuroendoscopic operation indications,operation excision,risk aversion,and the operation skills.Methods The clinical data of 7 patients with giant invasive pituitary tumor among of endoscopic transsphenoidal surgery 61 cases of neurological patients with pituitary tumors were analyzed retrospectively.Results There were 1 case of total resection,6 cases of subtotal resection invading cavernous sinus cases,diaphragma sellar was seen in 5 cases of resection of the tumor,and 2 cases showed no diaphragma sellar.The average operation time was 100 minutes.No intraoperative transfusion.Postoperative hemorrhage in 2 cases,and 1 death case in this group after 36 hours,and 1 case undergoing endoscopic hematoma resection and cured.Conclusions With the development of endoscopic techniques,indications for operation with the new changes,for the giant invasive pituitary tumor operation therapy,endoscopic technique provides a disposable operation resection,the method is safe and avoid catastrophic consequences.