Pancreatic cancer is a highly malignant solid tumor of the digestive system with extremely poor treatment prognosis. Although its incidence rate is low， its mortality rate is extremely high. In recent years， the number of diagnosed cases worldwide has continued to rise， making pancreatic cancer the sixth leading cause of cancer-related deaths globally. Currently， clinical treatment primarily relies on operation and chemotherapy to suppress tumors. However， these approaches face challenges such as suboptimal efficacy， high postoperative recurrence rates， and severe adverse reactions. Therefore， identifying safe and effective treatment modalities remains a pressing challenge for the medical community. In recent years， research on traditional Chinese medicine （TCM） interventions for pancreatic cancer has increased significantly. Multiple studies have shown that single-herb TCM， TCM formulas， and their derived single compounds can regulate the levels of tumor cell signaling pathways through multiple action targets. They inhibit the development and progression of pancreatic cancer by inhibiting cancer cell proliferation， promoting cell apoptosis， inhibiting tumor angiogenesis， reducing cancer cell invasion and migration capabilities， regulating the cell cycle， and modulating the tumor microenvironment. Additionally， TCM has the advantages of significantly enhancing the anticancer efficacy of chemotherapy drugs and causing fewer adverse reactions. However， the specific action mechanisms by which TCM intervenes in pancreatic cancer remain unclear. Further extensive research is still needed to validate the role of regulating classical signaling pathways such as phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， nuclear transcription factor-κB （NF-κB）， notch， and hedgehog in the treatment of pancreatic cancer. Therefore， this paper reviewed Chinese and international studies on TCM intervention in pancreatic cancer through relevant signaling pathways in recent years， summarized the potential action mechanisms of TCM in the treatment of pancreatic cancer， and provided references for related research in the future.

Obesity， a global chronic disease， is associated with adipose tissue dysfunction， which is one of the contributing factors to obesity. The cyclic adenosine monophosphate （cAMP） signaling pathway， a key regulator of lipid metabolism， plays a pivotal role in obesity development. Various of traditional Chinese medicine monomers， such as flavonoids， lignans， phenols， and terpenoids， as well as traditional Chinese medicine compound formulas like Xiaoyao powder， Shengmai powder， and Zexie decoction， can maintain energy homeostasis， balance adipose tissue function， regulate glucose metabolism， improve insulin resistance， and suppress inflammatory responses through cAMP signaling pathway regulation， thereby intervening in lipid metabolism for obesity treatment. Although a substantial amount of basic research has preliminarily elucidated the potential mechanisms by which traditional Chinese medicine intervenes in obesity through the cAMP signaling pathway， clinical translational research remains inadequate. There is an urgent need for large-sample， high-quality randomized controlled trials to validate these findings.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

BackgroundNon-suicidal self-injury （NSSI） behavior is highly prevalent during adolescence. Previous studies have mainly focused on the relationship between NSSI behavior and emotional regulation， pain perception， reward mechanisms， and impulsivity. However， the cognitive mechanisms underlying the occurrence and maintenance of NSSI behavior have not been sufficiently explored. Adolescence is a critical period for the development of cognitive control. However， it remains unclear whether adolescents with depressive disorder accompanied by NSSI behavior have abnormal cognitive control. ObjectiveTo reveal the potential deficits in cognitive control among adolescents with depressive disorder accompanied by NSSI behavior. MethodsThis study was a case-control study including 166 adolescent patients who visited the Third People's Hospital of Lanzhou from November 2024 to May 2025 and met the diagnostic criteria for depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. According to whether they had NSSI behavior or not， patients were divided into the NSSI group （n=86） and the non-NSSI group （n=80）. At the same time， healthy adolescents who passed mental health screenings in five public middle schools in the northwest region were selected as the control group （n=71）. All participants completed the color-word Stroop task， and the accuracy rates and reaction time in congruent and incongruent conditions of each group were recorded， and the interference effect based on accuracy rates and reaction time was calculated. ResultsIn terms of accuracy rate， the main effect of trial type was statistically significant （F=46.900， P<0.01， ηp²=0.160）， and the interaction effect between group and trial type was also statistically significant （F=3.390， P=0.035， ηp²=0.028）. In terms of reaction time， the main effect of trial type was statistically significant （F=72.020， P<0.01， ηp²=0.240）， and the interaction effect between group and trial type was also statistically significant （F=6.400， P=0.002， ηp²=0.050）. Simple effect analysis revealed that under both congruent and incongruent conditions， the reaction time of the NSSI group was longer than those of the non-NSSI group and the control group， and the reaction time of the non-NSSI group was also longer than that of the control group （P<0.01）. There were statistically significant differences in the interference effects among three groups based on reaction time （H=10.231， P=0.006）. The interference effect in the NSSI group was higher than that in the control group （Z=3.012， P_adj=0.008） and the non-NSSI group （Z=2.453， P_adj=0.043）. There was no statistically significant difference in the interference effect among the three groups based on accuracy rate （H=5.666， P=0.059）. ConclusionAdolescents with depressive disorder accompanied by NSSI behavior exhibit cognitive control deficits beyond depressive symptoms， particularly showing impaired conflict suppression ability. ［Funded by Lanzhou Municipal Health Industry Scientific Research Project （number，A2026019）］

China bears a substantial disease burden of chronic hepatitis B （CHB）. Under current clinical management regimens for CHB， achieving functional cure （also termed clinical cure） is the core goal for the treatment of patients meeting treatment indications. To achieve the goal of functional cure， drug regulatory authorities in China and globally have successively issued technical criteria to provide guidance for the overall design and scientific evaluation of clinical trials for innovative drugs. However， the rapid development in scientific research， clinical practice， and new drug research and development in this field has brought new challenges， especially those concerning the assessment of the clinical value of investigational drugs. This article reviews the current status of clinical research and development of new drugs for achieving the functional cure of CHB worldwide， analyzes the characteristics of available clinical trial data， and focuses on key aspects of pivotal clinical trials for CHB functional cure drugs， including target populations （baseline HBsAg level）， HBsAg seroclearance response， HBsAg seroreversion after drug withdrawal， and clinically meaningful target threshold of functional cure response rate， in order to provide a reference for further refinement of related technical criteria.

ObjectiveTo investigate the association between sarcopenia and short-term prognosis in patients with acute-on-chronic liver failure （ACLF）， to assess the value of Model for End-Stage Liver Disease （MELD）， MELD combined with serum sodium concentration （MELD-Na）， MELD 3.0， and Chinese Group on the Study of Severe Hepatitis B （COSSH）-ACLF Ⅱ score in predicting the 90-day prognosis of ACLF patients， and to analyze the predictive gain of sarcopenia over traditional prognostic scoring models. MethodsA retrospective study was conducted among 219 patients with ACLF who were hospitalized in The Affiliated Hospital of Inner Mongolia Medical University， No. 2 Hospital of Hohhot， Hohhot First Hospital， and Inner Mongolia People’s Hospital from July 2018 to July 2024. L3 skeletal muscle index （L3-SMI） was measured and calculated based on abdominal computed tomography images， and sarcopenia was diagnosed based on L3-SMI. According to 90-day prognosis， the patients with ACLF were divided into survival group with 124 patients and death group with 95 patients. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariate Cox regression analysis （stepwise backward approach） was used to identify independent risk factors for 90-day mortality in ACLF patients. The Kaplan-Meier method was used for survival analysis， and the Log-rank test was used for comparison between groups. The receiver operating characteristic curve was plotted to evaluate the predictive performance of each model， and the DeLong test， bootstrap internal validation， net reclassification improvement （NRI）， and integrated discrimination improvement （IDI） were used to assess the predictive gain of sarcopenia. ResultsThe multivariate Cox regression analysis showed that presence of sarcopenia （hazard ratio ［HR］=3.385， 95% confidence interval ［CI］： 1.722 — 6.657， P<0.05）， older age （HR=1.036， 95%CI： 1.017 — 1.056， P<0.05）， elevated alkaline phosphatase （HR=1.006， 95%CI： 1.004 — 1.009， P<0.05）， elevated total bilirubin （HR=1.003， 95%CI： 1.001 — 1.005， P<0.05）， elevated potassium （HR=1.581， 95%CI： 1.160 — 2.155， P<0.05）， elevated serum creatinine （HR=1.015， 95%CI： 1.007 — 1.024， P<0.05）， and prolonged prothrombin time （HR=1.035， 95%CI： 1.015 — 1.055， P<0.05） were independent risk factors for 90-day mortality in ACLF patients， while elevated albumin （HR=0.885， 95%CI： 0.837 — 0.935， P<0.05） was an independent protective factor against 90-day mortality. MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ scores had an area under the ROC curve （AUC） of 0.569， 0.570， 0.632， and 0.659， respectively， for predicting the 90-day prognosis of ACLF patients， suggesting that these scores had unsatisfactory performance； after they were respectively combined with sarcopenia， the AUC was increased to 0.702， 0.687， 0.723， and 0.728， respectively. The DeLong test， NRI， and IDI analyses showed the combined models had significantly better predictive performance （all P<0.05）. ConclusionSarcopenia is an independent risk factor for 90-day mortality in patients with ACLF. Traditional scoring models have limited predictive performance for 90-day prognosis in ACLF patients， and the combination with sarcopenia significantly improves predictive value， suggesting that sarcopenia can be used as an important supplementary indicator for prognostic evaluation of ACLF in clinical practice.

BACKGROUND:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective:To construct a full-length infectious clone of enterovirus D68（EV-D68）expressing enhanced green fluorescent protein（EGFP）by reverse genetics in order to provide an efficient tool for studying the biological characteristics and screening antiviral drugs for EV-D68.Methods:Gene synthesis and overlap PCR techniques were used to construct the full-length clone plasmid pUC57-EV-D68 of EV-D68. The full-length viral sequence was then transferred into the pCAGGS plasmid to obtain the pCAGGS-EV-D68 plasmid. The EGFP gene was amplified and inserted into the pCAGGS-EV-D68 plasmid to construct the pCAGGS-EGFP-EV-D68 plasmid. Then，the two constructed plasmids were transfected into human rhabdomyosarcoma（RD）cells to rescue recombinant viruses RV-EV-D68 and RV-EGFP-EV-D68. The rescued viruses were identified using PCR，Western blot，and immunofluorescence techniques. The antiviral effect of doxycycline was evaluated using the rescued RV-EGFP-EV-D68. Statistical analysis was performed using the two independent samples t-test. Results:The recombinant virus RV-EGFP-EV-D68 capable of expressing EGFP was successfully rescued. Even after 15 serial passages，the virus retained EGFP expression with no significant difference in viral titers compared to the parental virus，indicating its stable passage in RD cells. Besides，the rescued strains exhibited similar replication characteristics to the parental virus. While at 24 and 36 h after infection，the titers of the rescued strains were significantly lower than that of the parental strain（both P<0.05）. This study demonstrated that doxycycline significantly reduced the fluorescence intensity of RV-EGFP-EV-D68-infected RD cells（ P<0.01）. Meanwhile，a negative correlation was observed between the doxycycline concentration and the fluorescence intensity，indicating that the rescued virus could be used for antiviral drug evaluation. Conclusions:This study successfully constructs an infectious clone of EV-D68 expressing EGFP. The rescued recombinant virus RV-EGFP-EV-D68 has been verified to be applicable for the evaluation of antiviral drugs.