To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

Adipose-derived mesenchymal stem cells (ADSCs) are prominent candidates for regenerative medicine owing to their accessibility and multilineage differentiation potential. Nonetheless, clinical translation is limited by poor survival, differentiation, and migration after transplantation. To overcome these challenges, various pretreatment strategies have been developed to enhance their therapeutic efficacy. This review summarizes recent advances in ADSC pretreatment, focusing on methods that improve their survival, integration, and function in therapeutic applications. Physical, chemical, and biological pretreatments are discussed, including hypoxic conditioning, pharmacological interventions, and cytokine pre-incubation, all of which serve to precondition ADSCs for enhanced regenerative performance. These developments hold promise for enhancing the therapeutic potential of ADSCs and offer new opportunities for their future clinical application.

BACKGROUND:Previous studies have found that growth arrest and DNA damage-inducible protein 45β(Gadd45b)is beneficial to the repair of acute cerebral ischemia,but the action mechanism is still unclear.OBJECTIVE:To investigate the effect and mechanism of Gadd45b on white matter demyelinating lesions in rats with chronic cerebral ischemia.METHODS:SD rats were randomly divided into four groups:sham operation group,model group,empty vector group,and Gadd45b overexpression group,with 15 rats in each group.Gadd45b-overexpressing lentivirus and no-load lentivirus were injected into the bilateral hippocampus and bilateral ventricles of rats.One week after lentivirus transfection,the rat model of chronic hypoperfusion cerebral ischemia was established by bilateral common carotid artery ligation.Three weeks after the bilateral common carotid artery ligation,the learning and cognitive functions of rats were evaluated by novel object recognition test.Luxol fast blue staining was used to observe the changes of myelin structure in the corpus callosum of rats.Hematoxylin-eosin staining and Nissl staining were used to observe the damage of the rat corpus callosum.Immunofluorescence staining was used to detect the expression of myelin basic protein and neurofilament protein 200 in the corpus callosum of rats.Immunofluorescence double staining was used to detect the expression of astrocyte markers GFAP/C3d and GFAP/S100A10 in rat brain tissue.ELISA was used to detect the levels of tumor necrosis factor-α and interleukin-6 in the supernatant of brain tissue.RESULTS AND CONCLUSION:(1)Gadd45b overexpression could significantly improve the learning and cognitive function of rats with chronic cerebral ischemia,and improve demyelination and pathological damage in the rat corpus callosum.(2)The results of immunofluorescence showed that Gadd45b overexpression significantly increased the expression levels of myelin basic protein and neurofilament protein 200 in the brain tissue of rats with chronic cerebral ischemia.(3)Gadd45b overexpression reduced GFAP/C3d double positive cells and increased GFAP/S100A10 double positive cells in the brain tissue of rats with chronic cerebral ischemia.(4)Gadd45b overexpression reduced the levels of tumor necrosis factor-α and interleukin-6 in the brain tissue of rats with chronic cerebral ischemia.It is concluded that Gadd45b overexpression improves cognitive dysfunction by promoting the A2 phenotype transformation of astrocytes,alleviating white matter myelin structure damage and neuroinflammation in rats with chronic cerebral ischemia.

Objective To explore the relationship between gut microbiota and adult hippocampal neu-rogenesis(AHN)in the prevention of age-related neurological decline by aerobic exercise,and to clar-ify the role of microbiota-gut-brain axis in exercise enhancing AHN.Methods Sixteen 52-week-old SPF C57BL/6 male mice were randomly divided into an old control group(OC)and an old aerobic ex-ercise group(OE),each of 8.The OE group underwent 16-week incremental load treadmill exercise,while the control group kept quiet.After the intervention,the contents of 5-Hydroxytryptamine(5-HT),γ-aminobutyric acid(GABA)and Dopamine(DA)in hippocampus were detected using ELISA,while those of glutamic amino acid(Glu)in hippocampus,as well as Acetylcholine(Ach)in hippocam-pus and serum was determined by using the ultraviolet colorimetric method.Moreover,hippocampal in-sulin-like growth factors 1(IGF1)and vascular epithelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)proteins expression were measured using Western blotting.Meanwhile,fe-cal samples were collected for microbiota analysis by 16S rDNA sequencing.Results① After 16-week aerobic exercise,compared with the OC group,the contents of 5-HT and Glu(P<0.01),DA and GA-BA(P<0.05)in hippocampus increased in the OE group.Moreover,the hippocampal and serum Ach levels in the OE group increased significantly,compared to the OC group(P<0.01).②Compared with the OC group,the expression of BDNF,VEGF and IGF1 in the OE group increased significantly(P<0.01)after 16-week aerobic exercise.③Compared with the OC group,the diversity of microbiota in the OE group increased significantly(P<0.01)after the intervention.Moreover,the relative abundance of bacteroidetes and tenericutes increased,while that of proteobacteria decreased significantly in the OE group(P<0.01).Conclusions The composition of gut microbiota and the expression of central neu-rotransmitters in aged mice were significantly improved after 16-week incremental load aerobic exer-cise.Moreover,the expression of hippocampal neurogenesis related factors and the content of central neurotransmitters in adult individuals were promoted.The microbiota-gut-brain axis plays an important role in exercise improving AHN in aged mice.

Objective To explore the relationship between gut microbiota and adult hippocampal neu-rogenesis(AHN)in the prevention of age-related neurological decline by aerobic exercise,and to clar-ify the role of microbiota-gut-brain axis in exercise enhancing AHN.Methods Sixteen 52-week-old SPF C57BL/6 male mice were randomly divided into an old control group(OC)and an old aerobic ex-ercise group(OE),each of 8.The OE group underwent 16-week incremental load treadmill exercise,while the control group kept quiet.After the intervention,the contents of 5-Hydroxytryptamine(5-HT),γ-aminobutyric acid(GABA)and Dopamine(DA)in hippocampus were detected using ELISA,while those of glutamic amino acid(Glu)in hippocampus,as well as Acetylcholine(Ach)in hippocam-pus and serum was determined by using the ultraviolet colorimetric method.Moreover,hippocampal in-sulin-like growth factors 1(IGF1)and vascular epithelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)proteins expression were measured using Western blotting.Meanwhile,fe-cal samples were collected for microbiota analysis by 16S rDNA sequencing.Results① After 16-week aerobic exercise,compared with the OC group,the contents of 5-HT and Glu(P<0.01),DA and GA-BA(P<0.05)in hippocampus increased in the OE group.Moreover,the hippocampal and serum Ach levels in the OE group increased significantly,compared to the OC group(P<0.01).②Compared with the OC group,the expression of BDNF,VEGF and IGF1 in the OE group increased significantly(P<0.01)after 16-week aerobic exercise.③Compared with the OC group,the diversity of microbiota in the OE group increased significantly(P<0.01)after the intervention.Moreover,the relative abundance of bacteroidetes and tenericutes increased,while that of proteobacteria decreased significantly in the OE group(P<0.01).Conclusions The composition of gut microbiota and the expression of central neu-rotransmitters in aged mice were significantly improved after 16-week incremental load aerobic exer-cise.Moreover,the expression of hippocampal neurogenesis related factors and the content of central neurotransmitters in adult individuals were promoted.The microbiota-gut-brain axis plays an important role in exercise improving AHN in aged mice.

Objective To prepare a stable rat model of chronic liver failure to provide a tool for basic research.Methods Sixty-six SPF SD rats were divided into a normal group(n=18)and a modeling group(n=48).Rats in the modeling group received an intraperitoneal injection of 50％CCl4 olive oil solution(1.5 mL/kg,twice a week).Multidimensional assessment was performed at 8,16,and 24 weeks,respectively,including ultrasonic examination of liver morphology,hardness,portal vein diameter,and ascites,and collection of serum,plasma,and liver tissue to detect liver function,coagulation function,and blood ammonia levels.Liver tissue injury and fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Cognitive function was assessed using the water maze test.Survival were recorded simultaneously.Results Rats in the model group showed decreased activity and appetite,yellow urine,and increased abdominal circumference compared with the normal group.Ultrasound showed enhanced liver parenchyma echo in the model group that thickened with time,secondary ascites formation,portal vein dilation,and portal hypertension.Water maze and blood ammonia tests confirmed cognitive decline(memory and orientation loss)and hepatic encephalopathy in the model group.Gross observation showed that the liver in the model group was atrophied and appeared rough and uneven.HE staining showed hepatocyte swelling,steatosis,and necrosis,and Masson staining confirmed fibrosis progression with pseudolobule formation.The liver function indexes AST,ALT,TBIL and blood ammonia continued to increase,and coagulation dysfunction(prolonged PT and increased INR)gradually increased with the modeling process.Conclusions Intraperitoneal injection of 50％CCl4 olive oil solution(1.5 mL/kg,every week)for 24 weeks can stably simulate persistent chronic liver injury in rats and lead to the typical pathological changes and complications of chronic liver failure,based on the decompensation stage of cirrhosis.This model replicates the pathological evolution of human hepatitis from liver fibrosis → liver cirrhosis compensation → decompensation → chronic liver failure,providing a reliable modeling reference for the study of the mechanism of chronic liver failure.

OBJECTIVE To investigate the activity and mechanism of tetrandrine(TET)against influenza A virus in vitro and in vivo.METHODS(1)Cell experiments.① Human non-small cell lung cancer cells(A549)were divided into TET 0(cell control),1.25,2.5,5,10,20 and 25 μmol·L-1 groups,and H1N1+TET 0,1.25,2.5,5,10,20 and 25 μmol·L-1 groups.The TET groups were treated with the corresponding concentrations of TET while the H1N1+TET groups were infected with H1N1 for 1 h before the corresponding concentrations of TET were added.After 48 h,cell viability was detected using the CCK-8 method.② The cells were divided into cell control,H1N1+TET 0,2.5,5,and 10 μmol·L-1 groups and treated as in ①.After 24 h of incubation,the mRNA expressions of matrix protein 1(M1),hemagglutinin(HA),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-β(IFN-β)were tested by the real-time quantitative PCR(RT-qPCR).The expression levels of M1,HA,neuraminidase(NA),nucleoprotein(NP),and phosphorylation of signal transducer and activator of transcription 3(STAT3)protein were detected by Western blotting.(2)Animal experiments.① Male BALB/c mice were randomly divided into the solvent control group,H1N1 group,H1N1+oseltamivir phosphate(Ose)20 mg·kg-1 group,and H1N1+TET 25,50 and 100 mg·kg-1 groups.The solvent control group and the H1N1 group were ig administered with 0.5％carboxymethyl cellulose sodium(CMC-Na),while the H1N1+Ose group and the H1N1+TET 25,50 and 100 mg·kg-1 groups were ig given suspensions of the respective concentrations of drugs in 0.5％CMC-Na.After three consecutive days of pretreatment,all these groups except the solvent control group were intranasally inoculated with H1N1 to establish an influenza-infected mouse model.The survival rate and body mass of mice were monitored and recorded for 15 consecutive days post-H1N1 infection.② The grouping and treatment were the same as ①.After infection,mice were sacrificed on day 3 and 5.The expression levels of M1,HA,TNF-α,IL-1βand IL-6in lung tissues were detected by RT-qPCR,and those of M1,HA,NA,NP,and phosphoryla-tion of STAT3 protein in mice lung tissues by Western blotting.Hematoxylin-Eosin(HE)staining was performed to observe the pathological changes of lung tissues in mice.The levels of IL-6,TNF-α and IFN-β in bronchoalveolar lavage fluid(BALF)were determined by enzyme-linked immunosorbent assays(ELISA).RESULTS(1)① The half maximal inhibitory concentration study showed a value of 18.06 μmol·L-1 for A549 effected by TET.Compared with the H1N1 group,TET 2.5,5 and 10 μmol·L-1 significantly increased cell viability.② The expression levels of M1,HA mRNA and M1,HA,NA protein in the TET 2.5,5 and 10 μmol·L-1 groups were significantly lowered compared with the H1N1 group.TET 5 μmol·L-1 significantly decreased H1N1-induced IL-6,TNF-α and IFN-β mRNA expression levels in A549 cells.TET 5 and 10 μmol·L-1 could significantly mitigate the phosphorylation of STAT3.(2)① Com-pared with the H1N1 group,TET 50 mg·kg-1 significantly improved the survival rate of H1N1-infected mice while TET 25 mg·kg-1 significantly elevated the body-weight of H1N1-infected mice.In the TET 50 mg·kg-1 group,expressions of HA and M1 mRNA,and HA,M1,NA and NP protein in the lung tissues of H1 N1-infected mice were significantly reduced compared with the H1N1 group.Compared with the H1N1 group,TET 50 mg·kg-1 significantly decreased the lung index,improved inflammatory lesions in lung tissues,inhibited the mRNA expressions of TNF-α,IL-6 and IFN-β in lung tissues,and down regu-lated the expressions of TNF-α,IL-6 and IFN-β proinflammatory cytokines in the BALF of the H1N1-infected mice.In addition,TET 50 mg·kg-1 also significantly inhibited STAT3 phosphorylation in lung tissues of mice infected with H1N1.CONCLUSION TET can inhibit H1N1 infection both in vivo and in vitro.The potential mechanism may be related to the inhibition of the IL-6/STAT3 pathway,which subse-quently suppresses the inflammatory response induced by H1N1.

Objective:To elucidate the role of solute carrier protein 7,family member 11(SLC7A11)/Glutathione peroxi-dase 4(glutathione peroxidase 4,GPx4)regulated ferroptosis pathway in the improvement of sarcopenia through aerobic exercise,and to identify a new target for the prevention and treatment of sarcopenia with exercise.Method:Twenty 52-week-old Specific pathogen Free(SPF)C57BL/6 male mice were randomly divided into the old control group(OC)and the old exercise group(OE).There were 10 mice in each group.Following one week of adaptive exercise,moderate-intensity exercise with incremental load was implemented as follows:14 m/min at 1-2 weeks,15 m/min at 3-4 weeks,16m/min at 5-10weeks,17m/min at 11-16weeks,60min/d,all with a slope of 0°.Gastrocnemius was harvested for ultrathin electron microscope sections.The levels of Glutathione(GSH),muscle glycogen and non-heme iron(non-heme iron)were measured by spectro-photometer.The serum ferritin(SF),mitochondrial 8-hydroxy-2 deoxyguanosine(8-OHdG)and 4-Hydroxynone-na(4-HNE)were measured by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of iron metabolism-related proteins,such as GPx4,SLC7A11,ferroportin 1(FPN1)and ferri-tin heavy chain 1(FTH1)in gastrocnemius muscle.Result:①Compared with OC,the wet weights of quadriceps femoris and gastrocnemius in OE were signifi-cantly increased(P＜0.01).In the exercise group,mitochondrial cristae arranged neatly and densely,and the light and dark bands of myofilaments were clear.In the aged control group,the mitochondrial cristae of gas-trocnemius muscle were disrupted,vacuolated or pyknotic,showing typical features of ferroptosis.② The SF and the iron content of gastrocnemius muscle were decreased in OE(P＜0.01).③ The levels of 4-HNE and 8-OHdG in gastrocnemius muscle of OE were significantly lower than those of OC(P＜0.01).The GSH content in gastrocnemius of OE was significantly higher than that of OC(P＜0.01).④ The expressions of SLC7A11,GPx4,FPN1 and FTH1 in gastrocnemius muscle of OE were significantly higher than those of OC(P＜0.01).Conclusion:Moderate aerobic exercise can prevent age-related sarcopenia by activating the SLC7A11/GPx4 pathway and inhibiting mitochondrial ferroptosis.

OBJECTIVE To investigate the activity and mechanism of tetrandrine(TET)against influenza A virus in vitro and in vivo.METHODS(1)Cell experiments.① Human non-small cell lung cancer cells(A549)were divided into TET 0(cell control),1.25,2.5,5,10,20 and 25 μmol·L-1 groups,and H1N1+TET 0,1.25,2.5,5,10,20 and 25 μmol·L-1 groups.The TET groups were treated with the corresponding concentrations of TET while the H1N1+TET groups were infected with H1N1 for 1 h before the corresponding concentrations of TET were added.After 48 h,cell viability was detected using the CCK-8 method.② The cells were divided into cell control,H1N1+TET 0,2.5,5,and 10 μmol·L-1 groups and treated as in ①.After 24 h of incubation,the mRNA expressions of matrix protein 1(M1),hemagglutinin(HA),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-β(IFN-β)were tested by the real-time quantitative PCR(RT-qPCR).The expression levels of M1,HA,neuraminidase(NA),nucleoprotein(NP),and phosphorylation of signal transducer and activator of transcription 3(STAT3)protein were detected by Western blotting.(2)Animal experiments.① Male BALB/c mice were randomly divided into the solvent control group,H1N1 group,H1N1+oseltamivir phosphate(Ose)20 mg·kg-1 group,and H1N1+TET 25,50 and 100 mg·kg-1 groups.The solvent control group and the H1N1 group were ig administered with 0.5％carboxymethyl cellulose sodium(CMC-Na),while the H1N1+Ose group and the H1N1+TET 25,50 and 100 mg·kg-1 groups were ig given suspensions of the respective concentrations of drugs in 0.5％CMC-Na.After three consecutive days of pretreatment,all these groups except the solvent control group were intranasally inoculated with H1N1 to establish an influenza-infected mouse model.The survival rate and body mass of mice were monitored and recorded for 15 consecutive days post-H1N1 infection.② The grouping and treatment were the same as ①.After infection,mice were sacrificed on day 3 and 5.The expression levels of M1,HA,TNF-α,IL-1βand IL-6in lung tissues were detected by RT-qPCR,and those of M1,HA,NA,NP,and phosphoryla-tion of STAT3 protein in mice lung tissues by Western blotting.Hematoxylin-Eosin(HE)staining was performed to observe the pathological changes of lung tissues in mice.The levels of IL-6,TNF-α and IFN-β in bronchoalveolar lavage fluid(BALF)were determined by enzyme-linked immunosorbent assays(ELISA).RESULTS(1)① The half maximal inhibitory concentration study showed a value of 18.06 μmol·L-1 for A549 effected by TET.Compared with the H1N1 group,TET 2.5,5 and 10 μmol·L-1 significantly increased cell viability.② The expression levels of M1,HA mRNA and M1,HA,NA protein in the TET 2.5,5 and 10 μmol·L-1 groups were significantly lowered compared with the H1N1 group.TET 5 μmol·L-1 significantly decreased H1N1-induced IL-6,TNF-α and IFN-β mRNA expression levels in A549 cells.TET 5 and 10 μmol·L-1 could significantly mitigate the phosphorylation of STAT3.(2)① Com-pared with the H1N1 group,TET 50 mg·kg-1 significantly improved the survival rate of H1N1-infected mice while TET 25 mg·kg-1 significantly elevated the body-weight of H1N1-infected mice.In the TET 50 mg·kg-1 group,expressions of HA and M1 mRNA,and HA,M1,NA and NP protein in the lung tissues of H1 N1-infected mice were significantly reduced compared with the H1N1 group.Compared with the H1N1 group,TET 50 mg·kg-1 significantly decreased the lung index,improved inflammatory lesions in lung tissues,inhibited the mRNA expressions of TNF-α,IL-6 and IFN-β in lung tissues,and down regu-lated the expressions of TNF-α,IL-6 and IFN-β proinflammatory cytokines in the BALF of the H1N1-infected mice.In addition,TET 50 mg·kg-1 also significantly inhibited STAT3 phosphorylation in lung tissues of mice infected with H1N1.CONCLUSION TET can inhibit H1N1 infection both in vivo and in vitro.The potential mechanism may be related to the inhibition of the IL-6/STAT3 pathway,which subse-quently suppresses the inflammatory response induced by H1N1.