The Guidelines for Construction of Traditional Chinese Medicine Pharmacovigilance Systems in Medical Institutions （T/CACM 1563.2-2024） were the first special guideline in China to systematically assist medical institutions in establishing a pharmacovigilance system tailored to the characteristics of traditional Chinese medicine （TCM）. This guideline was jointly developed with 23 authoritative medical and research institutions in China， under the lead of the Institute of Basic Clinical Medicine， China Academy of Chinese Medical Sciences. The purpose of this guideline was to standardize pharmacovigilance work throughout the entire lifecycle of TCM （including research and development， marketing， and application） and to establish a four-dimensional framework of "organizational structure， institutional system， information platform， and vigilance activities". Key components included the establishment of a TCM Safety Committee， the construction of nine core systems， the development of an information platform that complies with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use （ICH） E2B standards， alongside the risk monitoring， identification， assessment， and control during clinical trials and post-marketing phases. Therefore， this guideline filled a significant gap in the systemic standards for TCM safety management within medical institutions. Strictly adhering to domestic and international laws and regulations， the guideline compilation involved multiple rounds of expert interviews， systematic evidence integration， and broad consensus. This guideline was specified to be applicable to medical institutions at all levels， primarily addressing core issues， including the difficulty in adverse reaction identification， low reporting rates， and incomplete risk management chains due to the complex composition and diverse application of TCM. The compilation process was scientific and rigorous， ensuring alignment with current national laws and regulations， and was registered internationally. In the future， implementation will be promoted through standardized training， tiered dissemination， as well as a post-effect evaluation and dynamic revision mechanism starting two years after publication. All these aimed to enhance medical institutions' proactive capabilities in preventing and controlling TCM safety risks， ensure patient medication safety， and promote the high-quality development of TCM.

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.

The Guidelines for Construction of Traditional Chinese Medicine Pharmacovigilance Systems in Medical Institutions （T/CACM 1563.2-2024） were the first special guideline in China to systematically assist medical institutions in establishing a pharmacovigilance system tailored to the characteristics of traditional Chinese medicine （TCM）. This guideline was jointly developed with 23 authoritative medical and research institutions in China， under the lead of the Institute of Basic Clinical Medicine， China Academy of Chinese Medical Sciences. The purpose of this guideline was to standardize pharmacovigilance work throughout the entire lifecycle of TCM （including research and development， marketing， and application） and to establish a four-dimensional framework of "organizational structure， institutional system， information platform， and vigilance activities". Key components included the establishment of a TCM Safety Committee， the construction of nine core systems， the development of an information platform that complies with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use （ICH） E2B standards， alongside the risk monitoring， identification， assessment， and control during clinical trials and post-marketing phases. Therefore， this guideline filled a significant gap in the systemic standards for TCM safety management within medical institutions. Strictly adhering to domestic and international laws and regulations， the guideline compilation involved multiple rounds of expert interviews， systematic evidence integration， and broad consensus. This guideline was specified to be applicable to medical institutions at all levels， primarily addressing core issues， including the difficulty in adverse reaction identification， low reporting rates， and incomplete risk management chains due to the complex composition and diverse application of TCM. The compilation process was scientific and rigorous， ensuring alignment with current national laws and regulations， and was registered internationally. In the future， implementation will be promoted through standardized training， tiered dissemination， as well as a post-effect evaluation and dynamic revision mechanism starting two years after publication. All these aimed to enhance medical institutions' proactive capabilities in preventing and controlling TCM safety risks， ensure patient medication safety， and promote the high-quality development of TCM.

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.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Objective:To observe the clinical efficacy of filiform needle combined with fire needles for cervical radiculopathy(CR)due to wind-cold obstructing the meridians. Methods:A total of 60 patients with CR due to wind-cold obstructing the meridians were randomized into an observation group and a control group,with 30 cases in each group.The control group was treated with filiform needle treatment,and the observation group was treated with additional fire needle point-pricking treatment.The visual analog scale(VAS)and 20-point scale of CR developed by Yasuhisa TANAKA(YT-20)were scored before treatment and after 1,2,3,and 4 weeks of treatments.The tenderness threshold was measured.The local skin temperature was measured by an infrared thermal imager.A safety evaluation was performed after treatment. Results:After treatment,the VAS score in the observation group at each time point was lower than that in the control group(P<0.05).The YT-20 score,tenderness threshold,and local skin temperature in the observation group were all higher than those in the control group(P<0.05).The VAS score in the observation group at each time point after treatment was lower than that before treatment(P<0.05),and the YT-20 score,tenderness threshold,and local skin temperature at each time point were higher than those before treatment(P<0.05).After 3 and 4 weeks of treatments,the VAS score in the control group was lower than that before treatment(P<0.05),and the YT-20 score,tenderness threshold,and local skin temperature were higher than those before treatment(P<0.05).The group factor effects of VAS and YT-20 scores,tenderness threshold,and local skin temperature between the two groups were statistically significant(P<0.05).There was no significant difference in the time effect and the interaction effect between time and group(P>0.05). Conclusion:Filiform needle combined with fire needle or applied alone both can relieve neck pain in patients with CR due to wind-cold obstructing the meridians,and improve the temperature of the neck.The combination of filiform needle and fire needle works more quickly and has better efficacy.

【Objective】 To investigate the development of adaptability in children aged 2 - 6, and to explore its influencing factors, so as to provide reference for promoting the development of adaptability in young children. 【Methods】 Data were from the National Nutrition and Health Systematic Survey for Children in China, and 3 319 children aged 2 - 6 and their parents from 28 sites across 14 provinces were recruited in this study.The Development Scale for Children Aged 0 - 6 years (WS/T 580-2017) was used to measure the developmental quotient of children′s adaptive ability, and a survey questionnaire was used to collect relevant information about children and their parents. 【Results】 Among 3 319 children aged 2 - 6, the proportion of slightly low or low level of adaptability, moderate adaptability development, good and excellent adaptability development was 7.68%,66.25% and 26.06%, respectively.The proportion of children aged 5 - 6 with good and excellent adaptability was lower in 3-year-old and 4-year-old groups (χ²=59.29, P<0.05).Multiple stepwise linear regression showed that children′s gender (β=0.06), gestational age of birth (β=-0.05), only child (β=-0.04), left-behind child (β=-0.04), the main caregiver (β=-0.06), and the education level of parents (β=0.09, 0.10), whether parents actively pay attention to children′s emotions (β=-0.06) and whether children play with homemade toys (β=-0.04) were the influencing factors of children′s adaptive development quotient.Girls, full-term children, only children, non-left-behind children, children with parents as main caregivers, parents with a high level of education, parents who often take the initiative to pay attention to children′s emotions, and children who play with homemade toys had a higher level of adaptability development quotient. 【Conclusions】 The development level of adaptability in children aged 2 - 6 in China is mostly above the average level and is related to multiple factors.Targeted intervention work can be carried out on relevant factors in order to promote the development of children′s adaptability.

Objective:To discuss the protective effect of carnosine(CAR)against oxygen-glucose deprivation/reoxygenation(OGD/R)-induced astrocyte(AS)injury,and to clarify its possible mechanism.Methods:The AS were divided into control group,model group(OGD/R group),OGD/R+CAR group(CAR group),and OGD/R+CAR+AMP-activated protein kinase(AMPK)activator AICAR group(CAR+AICAR group).MTT assay and green cyanine staining method were used to detect the survival rates and green cyanine staining positive rates of the AS in various groups;Annexin V-FITC/PI method and flow cytometry were used to detect the apoptotic rates of the AS in various groups;Western blotting method was used to detect the expression levels of AMPK,phosphorylated AMPK(p-AMPK),mammalian target of rapamycin(mTOR),phosphorylated mTOR(p-mTOR),microtubule-associated protein light chain 3B(LC3B),Beclin-1,and P62 proteins in the AS in various groups;immunofluorescence staining was used to observe the LC3B positive fluorescence intensities in the AS in various groups.Results:Compared with control group,the survival rate and green cyanine staining positive rate of the AS in OGD/R group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).Compared with OGD/R group,the survival rate and green cyanine staining positive rate of the AS in CAR group were increased(P＜0.01),the apoptotic rate of the AS was decreased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were decreased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were increased(P＜0.01).Compared with CAR group,the survival rate and green cyanine staining positive rate of the AS in CAR+AICAR group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).The LC3B immunofluorescence staining results were consistent with the Western blotting results.Conclusion:CAR has the protective effect on injury of the AS induced by OGD/R,and its molecular mechanism may be related to the inhibition of the AMPK/mTOR signaling pathway,thereby inhibiting autophagy.

AIM:To explore the efficacy of lenvatinib(Len)in enhancing the therapeutic effects of immune checkpoint inhibitor for hepatocellular carcinoma(HCC)and to delve into its immunomodulatory mechanisms within the tumor microenvironment.METHODS:The effects of various concentrations of Len on the migration of human umbilical vein endothelial cells(HUVECs)and the secretion of CXC chemokine ligand 10(CXCL10)were investigated,and the mechanism by which Len modulates CXCL10 secretion was validated.An orthotopic HCC model was established,and the mice bearing tumors were randomly allocated into 4 groups:PBS group,BMS-202(PD-1/PD-L1 inhibitor)group,Len group,and Len/BMS-202 group.The progression of the orthotopic liver tumors was monitored with small animal in vivo im-aging techniques.On the 13th day after the treatment,mice were sacrificed and tumor tissues were harvested for analysis.Immunofluorescence was employed to identify apoptosis,vascular architecture,and hypoxic status within the tumor tis-sue.The expression levels of proliferation marker Ki67,transforming growth factor-β(TGF-β),and the infiltration de-grees of CD4+T cells and CD8+T cells in the tumor tissue were monitored with immunohistochemistry.The secretion of im-mune factors interferon-γ(IFN-γ),CXCL10 and TGF-α in the mouse serum was quantified with ELISA.Above all data were followed by statistical analysis.RESULTS:(1)Len could facilitate endothelial cell migration within a specific range and potentiated the response of tumor cells to IFN-γ by blocking fibroblast growth factor receptor(FGFR),thereby increasing the secretion of CXCL10 from the tumor cells.(2)Compared with PBS group,tumor growth was slower in all treatment groups,with Len/BMS-202 group showing the most significant inhibition of tumor growth in tumor-bearing mice(P<0.05).(3)Compared with PBS group and monotherapy groups,Len/BMS-202 significantly promoted tumor tissue apoptosis and inhibited tumor cell proliferation(P<0.05).(4)Compared with PBS group and BMS-202 group,both Len group and Len/BMS-202 group manifested a substantial enhancement in pericytes coverage rate(P<0.01),concomitantly showing a marked improvement in hypoxic conditions(P<0.01).(5)Compared with PBS group and monotherapy groups,Len/BMS-202 group showed a significant increase in the infiltration of CD4+T cells and CD8+T cells within the tumor(P<0.01),along with a marked decrease in the expression of TGF-β(P<0.01).(6)Compared with PBS group,all treatment groups collectively induced varying degrees of secretion of IFN-γ,CXCL10 and TGF-α in mouse serum(P<0.05),with Len/BMS-202 group demonstrating the most pronounced effects(P<0.01).CONCLUSION:Lenvatinib may augment the therapeutic efficacy of BMS-202 in HCC by facilitating tumor vascular normalization,alleviating hypoxic conditions,and enhancing the secretion of CXCL10,thereby synergistically activating the tumor immune microenvironment.

Objective:To corelate thromboelastography (TEG)-related parameters and D-dimer and fibrinogen levels with the severity of preeclampsia and pregnancy outcomes in patients with preeclampsia.Methods:A case-control study was conducted involving 92 patients with preeclampsia who received treatment at Northwest Women's and Children's Hospital between March 2022 and September 2023 (patient group) and 92 healthy pregnant women who underwent routine check-ups during the same period (control group). All participants underwent TEG tests, and D-dimer and fibrinogen levels were measured. Intergroup comparisons were performed, and patients were categorized based on the severity of their condition. TEG parameters and D-dimer and fibrinogen levels were compared among patients with varying severities of preeclampsia. TEG-related parameters were correlated with D-dimer and fibrinogen levels. Adverse pregnancy outcomes in the patient group were statistically analyzed, and risk factors for these adverse outcomes in women with preeclampsia were identified.Results:In the patient group, the R and K values were (3.06 ± 0.36) minutes and (1.21 ± 0.14) minutes, respectively, both of which were significantly lower than those in the control group [(5.44 ± 0.61) minutes, (1.79 ± 0.21) minutes, t = 32.22, 22.04, both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in the patient group were (71.31 ± 7.63)°, (3.89 ± 0.41), (65.71 ± 7.01) mm, (2.22 ± 0.24) mg/L, and (4.51 ± 0.49) g/L, respectively, all of which were significantly higher than those in the control group [(64.85 ± 6.79)°, (2.19 ± 0.23), (58.96 ± 6.09) mm, (1.92 ± 0.21) mg/L, (3.75 ± 0.40) g/L, t = -6.06, -34.68, -6.97, -9.02, -11.52, all P < 0.001]. In the patient group, severe cases had significantly lower R and K values compared with mild cases, while the α angle, CI value, MA value, and D-dimer and fibrinogen levels were significantly higher in severe cases than in mild cases ( t = 11.06, 7.16, -8.01, -12.05, -3.91, -13.74, -8.269, all P < 0.001). In patients with preeclampsia, the R and K values were negatively correlated with D-dimer levels, and the R value was negatively correlated with fibrinogen level ( r = -0.504, -0.612, -0.493, all P < 0.05). In addition, the MA and CI values were positively correlated with D-dimer level, and the α angle was positively correlated with fibrinogen level ( r = 0.436, 0.534, 0.492, all P < 0.05). Among the participants, 41 women experienced adverse pregnancy outcomes. In patients with adverse pregnancy outcomes, the R and K values were (2.48 ± 0.25) minutes and (1.12 ± 0.14) minutes, which were significantly lower than those in patients without adverse pregnancy outcomes [(2.75 ± 0.29) minutes, (1.28 ± 0.13) minutes, t = 4.71, 5.67; both P < 0.001]. The α angle, CI value, MA value, and D-dimer and fibrinogen levels in patients with adverse pregnancy outcomes were (76.62 ± 8.01)°, (4.42 ± 0.46), (69.77 ± 7.06) mm, (2.57 ± 0.27) mg/L, and (4.97 ± 0.51) g/L, all of which were significantly higher than those in patients without adverse pregnancy outcomes [(67.04 ± 7.01)°, (3.46 ± 0.37), (62.45 ± 6.82) mm, (1.94 ± 0.21) mg/L, (4.14 ± 0.43) g/L, t = -6.11, -5.03, -11.09, -12.25, -8.46, all P < 0.001]. Logistic regression analysis indicated that R and K values were protective factors for adverse pregnancy outcomes ( OR < 1, P < 0.05), while MA value, α angle, CI value, and D-dimer and fibrinogen levels were independent risk factors ( OR > 1, P < 0.05). Conclusion:TEG-related parameters differ significantly between patients with preeclampsia and healthy pregnant women. These parameters are correlated with the severity of preeclampsia, as well as with D-dimer and fibrinogen levels. TEG-related parameters are risk factors for adverse pregnancy outcomes in patients with preeclampsia.