OBJECTIVE To systematically evaluate the effects of oral non-peptidic thrombopoietin receptor agonists （TPO-RAs） on hepatic enzyme in adult patients with immune thrombocytopenia. METHODS A comprehensive literature search was conducted in PubMed， Web of Science， CNKI， Wanfang database and the Chinese Medical Association Journal Full-Text Database to collect randomized controlled trials （RCTs） comparing oral non-peptidic TPO-RAs （intervention group） with placebo or conventional therapy （control group）. All databases were searched from their inception to June 2025. After literature screening， data extraction and quality assessment of the included studies， meta-analysis was conducted using RevMan 5.4.1 software. RESULTS Twelve RCTs comprising 1 388 patients were included， with 971 in the intervention group and 417 in the control group. Meta-analysis results showed that there were no significant differences between the two groups in terms of the incidence of hepatic enzyme elevation[OR＝1.24， 95%CI （0.77， 1.99）， P ＝0.37 ] ， the incidence of hepatic enzyme elevation in patients treated for ≥6 weeks[OR＝1.21， 95%CI （0.73， 1.99）， P ＝0.46 ] ， and the incidence of severe hepatic enzyme elevation[OR＝1.39， 95%CI（0.46， 4.20）， P ＝0.55 ] . Subgroup analysis showed that there were no significant differences in the incidence of hepatic enzyme elevation between the intervention group and control group among patients using eltrombopag[OR＝1.57，95%CI（0.85，2.87）， P ＝0.15 ] ， avatrombopag[OR＝0.88，95%CI （0.09，8.46）， P ＝0.91 ] ， and hetrombopag[OR＝1.04，95%CI（0.30，3.65）， P ＝0.95 ] ， respectively. CONCLUSIONS Oral non-peptidic TPO-RAs do not significantly increase the risk of hepatic enzyme elevation in adult patients with immune thrombocytopenia， and show an overall favorable hepatic safety profile.

Objective To implement the disease prevention and control strategy of being ^"proactive and grassroots-focused,^" and to enhance the overall effectiveness of general hospitals in the tertiary prevention of cervical cancer, this consensus aims to provide an actionable guiding framework for the standardized construction of ^"Integrated Outpatient Clinics for Cervical Cancer Prevention and Control^" in general hospitals at all levels. Methods This consensus systematically elaborates on the specific elements for establishing such integrated clinics and formulates the corresponding standards. Results It is anticipated that the consensus will promote the establishment of standardized, homogeneous, and high-efficiency frontline positions for cervical cancer prevention and control within general hospitals, thereby contributing to the strategic vision of accelerating the elimination of cervical cancer. Conclusion The formulation and promotion of the consensus aim to provide robust clinical practice support for accelerating the realization of China's strategic vision of eliminating cervical cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component （NUF2） and magnesium homeostasis in ovarian cancer cell apoptosis， as well as the regulatory mechanism of gypenoside L （Gyp-L） on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group， a low-concentration Gyp-L group （50 µmol·L^-1）， a high-concentration Gyp-L group （100 µmol·L^-1）， and a cisplatin （15 µmol·L^-1） group. The migration， proliferation， and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays， clonal experiments， and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus （GEO） database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes （STRING） database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource （TIMER） database， and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis （GEPIA） database. The mRNA expression levels of NUF2， magnesium homeostasis-related indicators， such as magnesium transporter 1 （MAGT1）， non-imprinted in Prader-Willi/Angelman syndrome 1 （NIPA1）， NIPA-like domain containing 1 （NIPAL1）， as well as apoptosis-related indicators B cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） in OVCAR3 cells， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NUF2， MAGT1， NIPA1， NIPAL1， Bcl-2， and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed， and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning， TUNEL staining， Real-time PCR， and ProteinSimple WES. Finally， the Mg²⁺ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis （P<0.05）. Overexpression of NUF2 markedly increased the expression levels of MAGT1， NIPA1， NIPAL1， and Bcl-2， while reducing the expression level of Bax （P<0.05）. It also significantly elevated intracellular Mg²⁺ content and protein synthesis efficiency and simultaneously inhibited apoptosis （P<0.05）. Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2， downregulating the expression levels of NUF2， MAGT1， NIPA1， NIPAL1， and Bcl-2 （P<0.05）， while upregulating the expression level of Bax （P<0.05）. ConclusionGyp-L can inhibit the occurrence of ovarian cancer， and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.

Allergic conjunctivitis is a common ocular inflammatory disease, with intense itching being the most typical and distressing symptom for patients. In recent years, with the in-depth study of the interaction between the nervous and immune systems, significant progress has been made in understanding the mechanism of itching in allergic conjunctivitis. This review elaborates on the neurobiological basis of itching in allergic conjunctivitis, with a focus on the complex dialogue between immune cells and sensory neurons, particularly the core role of the IL-33-ST2-CGRP signaling axis in mediating itching. Additionally, this article introduces new findings in genetic susceptibility research, including the identification of susceptibility genes for allergic conjunctivitis through transcriptome-wide association studies. The sensory nervous system not only transmits itch signals but also actively participates in the formation of antigen channels related to conjunctival goblet cells, thereby regulating the local uptake of allergens and the initiation of the immune response. Moreover, targeted novel therapeutic strategies offer hope for patients with refractory allergic conjunctivitis. Exploring the molecular and cellular mechanisms of itching in allergic conjunctivitis will provide a theoretical basis for the development of more effective treatment methods.

Gastroesophageal varices （GOV） bleeding is a severe complication of portal hypertension with a high mortality rate. Animal models are indispensable tools for investigating its pathogenesis and developing novel therapeutic strategies. This article systematically reviews the methods for establishing various GOV models， with a particular focus on their efficacy in simulating the key pathological processes such as an increase in hepatic venous pressure gradient and the risk of bleeding， and it also proposes targeted strategies for model selection. Finally， this article discusses the application prospects of emerging techniques in the era of precision medicine， such as organoids and gene editing， in order to provide model selection and a theoretical reference for exploring the mechanism and clinical translation of GOV.

Objective To investigate the relationship between the protective mechanism of dexmedetomidine(Dex)against myocardial ischemia-reperfusion(I/R)injury and cuproptosis.Methods The Langendorff models were con-structed using SD rats(I/R group),which were divided into 4 groups according to different interventions during reperfusion as:sham group,I/R group,Dex group and Dex+ES-Cu group.The left ventricular peak pressure(LVSP)of the rats in the above four groups were continuously monitored in the immediate pre-ischemic period(T0),30 min of reperfusion(T1),60 min reperfusion(T2),90 min reperfusion(T3),2 h of reperfusion(T4).Left ventricular end-diastolic pressure(LVEDP),heart rate(HR),maximum rate of rise of left ventricular pressure(+dp/dtmax)and maximum rate of drop.Subsequently,the extent of myocardial infarction was shown by 1%triphenyltetrazoliumchloride(TTC)staining,and the degree of myocardial fibrosis was assessed by Sirius red staining;Myocardial enzyme profiles,oxidative stress and inflammation indexes were detected by ELISA;Copper ions were detected by copper ion detection kit in myocardial tissues;ATF3,SPI1 and FDX1 protein level expres-sion was detected by Western blot.Results Compared with the sham-operated group,the extent of myocardial in-farction and fibrosis increased in the I/R group(P＜0.05),the level of serum MDA,IL-6,IL-1β,and TNF-α was elevated(P＜0.05),and the activity of SOD and GSH-Px decreased(P＜0.05).The Dex group significantly alleviated the above changes in the I/R group,and compared with the Dex group,in the Dex+ES-Cu group myocardi-al tissue copper ion content at the end of perfusion was increased(P＜0.05).Both ATF3 and SPI1 protein were in-creased and FDX1 protein was decreased(P＜0.05).Conclusions Dex can regulate copper metabolism and improve myocardial ischemia-reperfusion injury(MI/RI)resulted from oxidative stress and inflammation in rat model.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective To investigate the size variation in the first metatarsal of extant primates.Methods In this study,we analyzed 135 first metatarsal specimens across 12 primate genera,quantifying eight linear measurements,articular surface areas,mid-shaft cross-sectional area,total surface area,volume,and derived indices.Multivariate patterns were assessed through mean-based correspondence analysis and principal component analysis(PCA).Results Eulemur,Otolemur,Cebus,and Perodicticus exhibited a relatively high metatarsal surface-area-to-volume ratio.Perodicticus additionally showed a low articular facet index.Propithecus,Colobus,and Macaca displayed lower values for metatarsal shaft robusticity,the ratio of shaft cross-sectional area to base articular surface area,and the proximal articular facet index.Nasalis possessed a relatively high articular facet index.Pongo,Pan,Gorilla,and Homo sapiens were characterized by higher metatarsal shaft robusticity and a lower metatarsal surface-area-to-volume ratio.Principal component analysis revealed that the 12 extant primate genera could be broadly divided into two groups.Group 1 comprised Pongo,Pan,Gorilla and H.sapiens,although H.sapiens formed a distinct cluster relative to the extant great apes.Group 2 included Eulemur,Otolemur,Perodicticus,Propithecus,Cebus,Colobus,Macaca and Nasalis.Conclusion The relative sizedistribution of the first metatarsal provides some reference value for classifying extant primates.However,it demonstrates no clear correlations with specific locomotor patterns or foot grasping ability.