Objective To establish a high-performance liquid chromatography method to detect empagliflozin and related substances in empagliflozin bulk drug and tablets,and to provide technical support for quality control and unified monitoring of empagliflozin bulk drug and its tablets.Methods A liquid chromatography development system with the full factorial design of experiments and the Box-Behnken model was used to screen and optimize the chromatographic parameters.Related substances were detected in empagliflozin API and empagliflozin tablets from different companies with the optimized chromatographic parameters.Results The optimized chromatographic parameters were obtained:Shim-pack GIST C18-AQ column(250 mm×4.6 mm,5 μm)was used,column temperature was 15 ℃,gradient elution with water-acetonitrile as mobile phase was as below,flow rate was 1.2 mL·min-1,detection wavelength was set at 224 nm.The specificity of the method is good,with recoveries ranging from 94.8％to 101.7％,and RSD ranging from 0.5％to 3.1％.The known single impurity in APIs and tablets is less than 0.05％,any other unknown single impurity is less than 0.06％,and the total amount of impurities are less than 0.3％.The related substances of supervised sampling are under good control.Conclusion The method is reliable and robust for determining related substances of empagliflozin and its tablets.

Objective To evaluate the quality of propranolol hydrochloride tablets based on national drug sampling,to analyze existing quality issues and improve their quality standards,to provide references and suggestions for the production,quality control,and supervision of this product.Methods A comprehensive evaluation of 178 batches of sampled products was conducted using legal standards combined with exploratory research,including key quality indicators such as related substances,dissolution,content uniformity,content determination,in vitro dissolution profiles,and genotoxic impurity N-nitrosoproranolol.The quality of domestic propranolol hydrochloride tablets and the controllability of the current quality standards for product quality were assessed.Results According to the legal standard methods,the qualification rate of 178 batches of sampled products was 100%.Exploratory research revealed that the impurity levels of samples from six manufacturing enterprises were far below the limit requirements;however,differences existed in genotoxic impurity N-nitrosoproranolol and other aspects.Conclusions The overall quality of propranolol hydrochloride tablets is good,but the current standards need further improvement.It is recommended to add/revise the detection methods for related substances,content,and content uniformity,strictly control N-nitrosoproranolol,and urge enterprises to pay attention to the quality of excipients and the control of the preparation production process.

Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease(NAFLD)and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group(Chow group)and a methionine-choline-deficient(MCD)diet group(MCD group),with 10 mice per group.The MCD diet was used to induce NAFLD.Each group was further divided into two subgroups,resulting in four subgroups:Chow+saline,Chow+liraglutide,MCD+saline,and MCD+liraglutide group.After daily intraperitoneal injection of liraglutide(400 μg/kg)or an equivalent volume of saline for 4 weeks,an intraperitoneal glucose tolerance test(IPGTT)was performed.Serum levels of aspartate transaminase(AST),alanine aminotransferase(ALT),total cholesterol(TC),triglyceride(TAG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured.Liver tissues were collected post-euthanasia to assess TAG content.Histopathological changes,lipid deposition,and fibrosis were evaluated via hematoxylin-eosin(HE)staining,Oil Red O staining,and Masson staining.Real-time quantitative PCR(qPCR)and Western blotting were used to analyze the expression of α-smooth muscle actin(α-SMA),fibronectin(FN),collagen type Ⅰ α(COL1A),matrix metalloproteinase 9(MMP9),tissue inhibitor of metalloproteinase 1(TIMP1),transforming growth factor β(TGF-β),SMAD3,and phosphorylated SMAD3(pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15,30,and 60 min,with a decreased area under the curve(AUC)(both P<0.05).Biochemical analysis showed that liraglutide lowered AST and ALT levels(both P<0.001),increased TC and HDL-C levels(both P<0.05),but had no significant effect on TAG or LDL-C in MCD mice.HE staining and Oil Red O staining revealed reduced lipid droplets,ballooning degeneration,and inflammatory infiltration in hepatocytes after liraglutide treatment.Masson staining indicated decreased collagen fiber deposition in the liver.qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3,alongside downregulated MMP9 in MCD mice.Liraglutide reversed these changes,lowering α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury,lipid deposition,and fibrosis in NAFLD mice,through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.

Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease(NAFLD)and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group(Chow group)and a methionine-choline-deficient(MCD)diet group(MCD group),with 10 mice per group.The MCD diet was used to induce NAFLD.Each group was further divided into two subgroups,resulting in four subgroups:Chow+saline,Chow+liraglutide,MCD+saline,and MCD+liraglutide group.After daily intraperitoneal injection of liraglutide(400 μg/kg)or an equivalent volume of saline for 4 weeks,an intraperitoneal glucose tolerance test(IPGTT)was performed.Serum levels of aspartate transaminase(AST),alanine aminotransferase(ALT),total cholesterol(TC),triglyceride(TAG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured.Liver tissues were collected post-euthanasia to assess TAG content.Histopathological changes,lipid deposition,and fibrosis were evaluated via hematoxylin-eosin(HE)staining,Oil Red O staining,and Masson staining.Real-time quantitative PCR(qPCR)and Western blotting were used to analyze the expression of α-smooth muscle actin(α-SMA),fibronectin(FN),collagen type Ⅰ α(COL1A),matrix metalloproteinase 9(MMP9),tissue inhibitor of metalloproteinase 1(TIMP1),transforming growth factor β(TGF-β),SMAD3,and phosphorylated SMAD3(pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15,30,and 60 min,with a decreased area under the curve(AUC)(both P<0.05).Biochemical analysis showed that liraglutide lowered AST and ALT levels(both P<0.001),increased TC and HDL-C levels(both P<0.05),but had no significant effect on TAG or LDL-C in MCD mice.HE staining and Oil Red O staining revealed reduced lipid droplets,ballooning degeneration,and inflammatory infiltration in hepatocytes after liraglutide treatment.Masson staining indicated decreased collagen fiber deposition in the liver.qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3,alongside downregulated MMP9 in MCD mice.Liraglutide reversed these changes,lowering α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury,lipid deposition,and fibrosis in NAFLD mice,through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.

Objective To evaluate the quality of propranolol hydrochloride tablets based on national drug sampling,to analyze existing quality issues and improve their quality standards,to provide references and suggestions for the production,quality control,and supervision of this product.Methods A comprehensive evaluation of 178 batches of sampled products was conducted using legal standards combined with exploratory research,including key quality indicators such as related substances,dissolution,content uniformity,content determination,in vitro dissolution profiles,and genotoxic impurity N-nitrosoproranolol.The quality of domestic propranolol hydrochloride tablets and the controllability of the current quality standards for product quality were assessed.Results According to the legal standard methods,the qualification rate of 178 batches of sampled products was 100%.Exploratory research revealed that the impurity levels of samples from six manufacturing enterprises were far below the limit requirements;however,differences existed in genotoxic impurity N-nitrosoproranolol and other aspects.Conclusions The overall quality of propranolol hydrochloride tablets is good,but the current standards need further improvement.It is recommended to add/revise the detection methods for related substances,content,and content uniformity,strictly control N-nitrosoproranolol,and urge enterprises to pay attention to the quality of excipients and the control of the preparation production process.

Objective To establish a high-performance liquid chromatography method to detect empagliflozin and related substances in empagliflozin bulk drug and tablets,and to provide technical support for quality control and unified monitoring of empagliflozin bulk drug and its tablets.Methods A liquid chromatography development system with the full factorial design of experiments and the Box-Behnken model was used to screen and optimize the chromatographic parameters.Related substances were detected in empagliflozin API and empagliflozin tablets from different companies with the optimized chromatographic parameters.Results The optimized chromatographic parameters were obtained:Shim-pack GIST C18-AQ column(250 mm×4.6 mm,5 μm)was used,column temperature was 15 ℃,gradient elution with water-acetonitrile as mobile phase was as below,flow rate was 1.2 mL·min-1,detection wavelength was set at 224 nm.The specificity of the method is good,with recoveries ranging from 94.8％to 101.7％,and RSD ranging from 0.5％to 3.1％.The known single impurity in APIs and tablets is less than 0.05％,any other unknown single impurity is less than 0.06％,and the total amount of impurities are less than 0.3％.The related substances of supervised sampling are under good control.Conclusion The method is reliable and robust for determining related substances of empagliflozin and its tablets.

Growth arrest and DNA damage-inducible 45b(GADD45b)was initially discovered to be involved in processes such as cell cycle arrest,differentiation and apoptosis.It is an important signal regulatory molecule in cells,responsible for signal transduction under various physiological or environmental stimuli.The GADD45b gene belongs to the GADD45 gene family.This gene is commonly expressed in human and fetal tissues,but the expression is tissue-specific,with high expression in the liver and bone marrow.The GADD45b protein is a small,evolutionarily conserved acidic protein distributed in both the cytoplasm and nucleus.Research has shown that GADD45b is closely associated with signaling pathways such as p38/MAPK and TGFβ/Smad3,and it has functions including improving tissue fibrosis and inflammation progression,inhibiting cell autophagy,and enhancing neural function recovery.GADD45b plays a significant role in tumors,innate immunity,neurological diseases,and disorders of hepatic glucose and lipid metabolism.The incidence of non-alcoholic fatty liver disease(NAFLD)is increasing year by year in China and has become a serious public health issue in the country.Disorders in hepatic glucose and lipid metabolism are major causes of NAFLD.Multiple studies have shown that GADD45b gene and protein exhibit abnormal expression in liver diseases with hepatic glucose and lipid metabolism disorders.Previous research has found that GADD45b can increase the stability of the FoxO1 protein in hepatocytes,and enhance the expression of PGC1a,thereby promoting hepatic gluconeogenesis.Additionally,GADD45b can inhibit fatty acid transport in hepatocytes by binding to FABP1 and reduce hepatic steatosis by interacting with HSP72 protein.Therefore,the roles of GADD45b in promoting hepatic gluconeogenesis,inhibiting fatty acid transport,and reducing steatosis may form the basis for research into treatments for hepatic glucose and lipid metabolism disorders and liver diseases.This paper reviews the characteristics and functions of the GADD45b protein,as well as recent advances in the study of hepatic glucose and lipid metabolism and liver diseases,aiming to provide reference for further GADD45b research.

Objective To explore the influence of different factors on the safe screw placement of the ulnar coronoid process based on the DR imaging measurement of the ulnar coronoid process.Methods During the period from July 2020 to November 2021,102 normal adult elbow joint DR films were randomly included from Yunnan Provincial Hospital of Traditional Chinese Medicine.Standard elbow joint DR films were selected as the measurement objects,with the apex of the coronoid process as the vertex and two straight lines parallel to the elbow joint space along both sides of the coronoid process.The length of the line segment from the apex of the coronoid process to the intersection of the radius and ulnar cortex of the ulna was the safe distance to place the nail on the coronal surface of the ulna coronoid process;The standard lateral DR film of the elbow joint was selected as the measurement image,and the apex of the coronoid process was used as a point to draw out two safety lines intersecting with the ulnar cortex at the proximal and distal ends.The length of the safety lines at the proximal and distal ends of the coronoid process was the safe nail placement distance on the sagittal plane of the ulnar coronoid process.The differences in safe nail placement distance between different genders,left and right sides,were compared and the correlation between safe nail placement distances on different cross-sections was analyzed.Results There was a statistically significant difference in the safe placement distance of the ulnar coronoid process between males and females(P＜0.05);On the coronal plane,there was a correlation between the safe nail placement distance on the radial and ulnar sides in males;On the sagittal plane(P＜0.05),there was a correlation between the safe placement distance of the ulnar coronoid process in women's proximal and distal ends(P＜0.05).Conclusion Studying the safe screw placement distance of the ulnar coronoid process is beneficial to guide the clinical placement of screws for coronoid process fractures,the design of new steel plates,and the correction of deformity.

Objective Evaluation of the efficacy of high-frequency repetitive transcranial magnetic stimulation for chronic disturbance of consciousness after severe craniocerebral injury based on magnetic resonance spectroscopy.Methods The clinical data of 106 patients with chronic disturbance of consciousness after severe craniocerebral injury from January 2018 to December 2022 were retrospectively analyzed,and they were divided into control group(conventional rehabilitation treatment)and observation group(high frequency repetitive transcranial magnetic stimulation treatment)by propensity score matching method(1∶1),with 53 cases in each group.Both groups were examined by magnetic resonance spectroscopy(MRS)before and after treatment.The brain metabolic indexes[N-acetyl aspartate(NAA)/creatine(Cr)value,choline complex(Cho)/Cr value],Glasgow coma scale(GCS)score,electroencephalogram(EEG)grading,coma recovery scale(CRS-R)score,brainstem auditory evoked potential(BAEP)grading,upper limb sensory evoked potential(SSEP)grading and Cerebral blood flow perfusion index[cerebral blood volume(CBV),mean transit time(MTT),cerebral blood flow(CBF)]were compared between the two groups.Results After treatment,the NAA/Cr values of the thalamus and brainstem in the two groups increased,while the Cho/Cr values decreased,and the levels of brain metabolic indexes in the observation group were signifi-cantly better than those in the control group(P<0.05).The two groups'GCS score and CRS-R score increased,and the improvement of the observation group was better than that of the control group(P<0.05).The BAEP grading,EEG grading,and SSEP grading of the two groups improved,and those of the observation group were better than the control group(P<0.05).The CBF and CBV of the two groups increased,and MTT decreased,and the level of cere-bral blood perfusion index in the observation group was better than that in the control group(P<0.05).Conclusion High frequency repetitive transcranial magnetic stimulation has a significant effect on the recovery of patients with chronic consciousness disorders after severe craniocerebral injury.The mechanism may be related to improving the blood flow velocity of brain tissue and metabolism in the brain.

Objective To investigate the mechanism by which Liraglutide improves the inflammatory response in metabolic associated fatty liver disease(MAFLD)by regulating the interferon gene stimulating factor(STING)signaling pathway.Methods 20 male C57BL/6J mice were randomly divided into normal diet group(NC),Liraglutide intervention group(NC+Lir group),high fat diet group(HFD group)and Liraglutide intervention high fat diet group(HFD+Lir group),with 5 in each group.Mouse primary hepato-cytes(MPHs)were divided into normal control(Con)group,Liraglutide intervention group(Con+Lir group),palmitic acid group(PA group)and Liraglutide intervention PA group(PA+Lir group).The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and triglyceride(TG)contents in liver were detected.HE and oil red O staining were used to observe the pathological changes in the liver and to calculate the MAFLD activity score(NAS).The mRNA expression levels of STING,IL-1β and TNF-α in tissues and cells were detected by qRT-PCR.The protein expression levels of STING,p-IRF3 and IFN-β were detected by Western blot.Results Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD group were higher than those in NC group(P＜0.05 or P＜0.01).Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD+Lir group were lower than those in HFD group(P＜0.05 or P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in liver of HFD group were higher than those of NC group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in HFD+ Lir group were lower than those in HFD+ Lir group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA group were higher than those in Con group(P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA+Lir group were lower than those in PA group(P＜0.05 or P＜0.01).Conclusion Liraglutide ameliorates the high-fat-induced inflammation responses in MAFLD by regulating the STING signaling pathways.