OBJECTIVE To systematically sort out the drugs causing drug-induced liver injury （DILI） and their relevant information， and to develop the Expert consensus on the medication catalog for drug-induced liver injury and rational drug use （hereinafter referred to as the Consensus）， so as to provide a reference for rational clinical use. METHODS Systematic searches were conducted across various literature databases， guideline retrieval websites and professional liver injury websites. Drugs identified as causing DILI from the included literature and online resources were extracted and assigned scores based on source credibility： three points for LiverTox A-class drugs and two points for B-class drugs； two points for drugs from Hepatox and guidelines； and one point for drugs from consensus and related literature sources. Drugs classified as LiverTox category A/B or with total scores ≥4 were included in the preliminary list of DILI-causing drugs. Opinions were collected and integrated from a multidisciplinary expert panel comprising 45 medical and pharmaceutical experts from 27 provinces across China through three rounds of the Delphi method （including questionnaires and discussion sessions）， and after revision， the final version of Consensus was formed. RESULTS & CONCLUSIONS This Consensus included 12 traditional Chinese medicines （TCMs） such as Polygoni Multiflori Radix and Ephedrae Herba， 151 Western medicines including amiodarone and atorvastatin， along with rational use information. For TCM， eight rational use information were included： evidence-based score， liver injury classification based on pathogenesis， liver injury classification based on biochemical abnormality pattern， clinical phenotype， laboratory examination manifestations， latency period， recovery time， and management strategies. For Western medicines， six additional items were included based on the TCM， namely liver function monitoring， discontinuation， contraindications， cautions， dose adjustments， and risk factors， totaling 14 items. This Consensus systematically compiles DILI drugs and their rational use information， which will support clinicians in enhancing the prevention， identification， and management of DILI， reducing the incidence of liver injury， and ensuring patient medication safety and efficacy.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To explore the influencing factors of olfactory dysfunction in patients with Parkinson's disease(PD)and conduct a systematic review and Meta-analysis.Methods Articles on factors influencing olfactory dysfunction in PD were retrieved from databases including SinoMed,VIP,China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,Web of Science,PubMed,Cochrane,Embase,and MEDLINE.The search period spanned from the inception of each database to November 30,2024.Results A total of 13 articles(with a total sample size of 2465)were included,with a total of 18 influencing factors summarized as two themes:core features and progression factors of PD,and individual background and environmental interaction factors.Meta-analysis showed that age(MD=1.01,95％CI:-0.46-2.49,P=0.18),smoking(OR=0.88,95％CI:0.57-1.37,P=0.57),and constipation(OR=1.22,95％CI:0.38-3.93,P=0.74)were not factors affecting olfactory dysfunction in PD patients.Conclusion Factors influencing olfactory dysfunction in PD are predominantly associated with non-motor symptoms.Intervention strategies targeting non-motor symptoms(such as improving sleep quality,vitamin D supplementation,and early cognitive training)may provide novel approaches for delaying the progression of olfactory dysfunction.

Objective To investigate the effect of pneumoperitoneum pressure during robotic-assisted kidney transplantation (RAKT) on the function of the transplant kidney. Methods The data of 243 kidney transplant recipients were retrospectively analyzed and divided into open kidney transplantation (OKT) group (n=105) and RAKT group (n=138). The RAKT group was further divided into 13 mmHg group (n=67) and 7 mmHg group (n=71) based on pneumoperitoneum pressure. The donor information, recipient's preoperative general data, intraoperative data, and postoperative recovery of the three groups were compared. In the RAKT group, the renal artery, segmental artery, interlobar artery, and venous flow velocity of the transplant kidney were measured using laparoscopic ultrasound. Results There was a statistically significant difference in donor types among the groups (P<0.05), while other donor information and recipient's preoperative general data showed no statistically significant differences (all P>0.05). There were no statistically significant differences in serum creatinine and complications at 30 days and 1 year postoperatively among the groups (all P>0.05). The OKT group and 7 mmHg group had more intraoperative urine output than the 13 mmHg group. Both RAKT groups had less intraoperative blood loss and shorter hospital stays than the OKT group, and longer operation times than the OKT group (all P<0.05). There were no statistically significant differences in operation time, intraoperative blood loss, and hospital stay between the two RAKT groups (all P>0.05). The vascular flow velocity of the transplant kidney decreased at 13 mmHg compared to 7 mmHg pneumoperitoneum pressure, but the differences were not statistically significant (all P>0.05). Conclusions Controllable pneumoperitoneum pressure has a limited impact on the vascular flow velocity of the transplanted kidney. RAKT is a safe and effective surgical method under appropriate pneumoperitoneum pressure, and choosing a lower pneumoperitoneum pressure is more conducive to the early recovery of renal function postoperatively.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Colorectal cancer(CRC)is one of the most common malignant life-threatening tumors,with serious impacts on patient quality of life.Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)has recently become a hot topic in the field of cancer research,and has demonstrated a close relationship with CRC.SHP2,encoded by the PTPN11 gene,is a non-receptor tyrosine kinase commonly present in various tissues and cells of the human body.Existing research shows that SHP2 plays a crucial role in regulating CRC and colitis-associated colon cancer(CAC),and the emergence of SHP2 allosteric inhibitors has identified SHP2 as a potential new therapeutic target for patients with CRC.Here we review the structure of SHP2 and its roles in CRC and CAC.

Objective To investigate the protective effect of hederagenin(HDG)on cisplatin(Cis)-induced acute kidney injury(AKI)in mice and its potential mechanism.Methods 24 male C57BL/6J mice were randomly divided into a control group,AKI model group,HDG low-dose group,and HDG high-dose group,with six mice in each group.AKI model was established by intraperitoneal injection of 20 mg/kg cisplatin(Cis).The HDG low-dose and HDG high-dose groups were given 20,40 mg/kg HDG by intragastric administration,respectively,and samples were collected 3 days later.The kidneys of the mice were collected for hematoxylin-eosin(HE)and periodic-acid-schiff(PAS)staining to evaluate the kidney pathology,and serum was collected to detect changes in serum creatinine(Scr)and blood urea nitrogen(BUN).The expression of p-P65,P65,IL-6,TNF-α,IL-1β,and other inflammatory-related proteins was detected by Western Blot.A TCMK1(renal tubular epithelial cell)inflammatory cell model was established by Cis(200 ng/mL)stimulation in vitro.Blank group,Cis model group,HDG low-dose group,HDG high-dose group,Axin2 overexpression group,HDG+Axin2 overexpression group were set up.In the Axin2-overexpression group,the expression of p-P65,P65,IL-6,TNF-α,IL-1β,Axin2,and AREG was detected among total cell proteins.Results Compared with the control group,AKI model mice exhibited significantly elevated serum creatinine and blood urea nitrogen levels(P<0.05),accompanied by pathological alterations including vacuolar degeneration of renal tubules,inflammatory cell infiltration,and glycogen deposition,and the expression of inflammation-related proteins(p-P65,TNF-α,IL-6,IL-1β)and Axin2 was markedly upregulated in AKI mice(P<0.05).HDG treatment induced a dose-dependent reduction in serum creatinine and blood urea nitrogen levels(high-dose>low-dose,P<0.05),alleviated renal histopathological damage,and concurrently suppressed the expression of these inflammatory mediators and Axin2(P<0.05).HDG was confirmed that dose-dependently inhibited Cis-induced upregulation of Axin2,and inflammatory cytokines in vitro experiments.Transcriptome sequencing revealed that Axin2 overexpression significantly increased amphiregulin(AREG)expression(P<0.05).Mechanistically,HDG reduced p-P65 phosphorylation by suppressing the Axin2/AREG axis(P<0.05),while Axin2 overexpression abolished the protective effects of HDG against Cis-induced renal tubular cell injury.Conclusions HDG protects against renal injury in AKI mice by reducing inflammation through the inhibition of Axin2/AREG axis activation.

Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.

Colorectal cancer(CRC)is one of the most common malignant life-threatening tumors,with serious impacts on patient quality of life.Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)has recently become a hot topic in the field of cancer research,and has demonstrated a close relationship with CRC.SHP2,encoded by the PTPN11 gene,is a non-receptor tyrosine kinase commonly present in various tissues and cells of the human body.Existing research shows that SHP2 plays a crucial role in regulating CRC and colitis-associated colon cancer(CAC),and the emergence of SHP2 allosteric inhibitors has identified SHP2 as a potential new therapeutic target for patients with CRC.Here we review the structure of SHP2 and its roles in CRC and CAC.

Objective To investigate the protective effect of hederagenin(HDG)on cisplatin(Cis)-induced acute kidney injury(AKI)in mice and its potential mechanism.Methods 24 male C57BL/6J mice were randomly divided into a control group,AKI model group,HDG low-dose group,and HDG high-dose group,with six mice in each group.AKI model was established by intraperitoneal injection of 20 mg/kg cisplatin(Cis).The HDG low-dose and HDG high-dose groups were given 20,40 mg/kg HDG by intragastric administration,respectively,and samples were collected 3 days later.The kidneys of the mice were collected for hematoxylin-eosin(HE)and periodic-acid-schiff(PAS)staining to evaluate the kidney pathology,and serum was collected to detect changes in serum creatinine(Scr)and blood urea nitrogen(BUN).The expression of p-P65,P65,IL-6,TNF-α,IL-1β,and other inflammatory-related proteins was detected by Western Blot.A TCMK1(renal tubular epithelial cell)inflammatory cell model was established by Cis(200 ng/mL)stimulation in vitro.Blank group,Cis model group,HDG low-dose group,HDG high-dose group,Axin2 overexpression group,HDG+Axin2 overexpression group were set up.In the Axin2-overexpression group,the expression of p-P65,P65,IL-6,TNF-α,IL-1β,Axin2,and AREG was detected among total cell proteins.Results Compared with the control group,AKI model mice exhibited significantly elevated serum creatinine and blood urea nitrogen levels(P<0.05),accompanied by pathological alterations including vacuolar degeneration of renal tubules,inflammatory cell infiltration,and glycogen deposition,and the expression of inflammation-related proteins(p-P65,TNF-α,IL-6,IL-1β)and Axin2 was markedly upregulated in AKI mice(P<0.05).HDG treatment induced a dose-dependent reduction in serum creatinine and blood urea nitrogen levels(high-dose>low-dose,P<0.05),alleviated renal histopathological damage,and concurrently suppressed the expression of these inflammatory mediators and Axin2(P<0.05).HDG was confirmed that dose-dependently inhibited Cis-induced upregulation of Axin2,and inflammatory cytokines in vitro experiments.Transcriptome sequencing revealed that Axin2 overexpression significantly increased amphiregulin(AREG)expression(P<0.05).Mechanistically,HDG reduced p-P65 phosphorylation by suppressing the Axin2/AREG axis(P<0.05),while Axin2 overexpression abolished the protective effects of HDG against Cis-induced renal tubular cell injury.Conclusions HDG protects against renal injury in AKI mice by reducing inflammation through the inhibition of Axin2/AREG axis activation.