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.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.

Objective:To explore the types and characteristics of self-management behaviors among stroke patients, as well as to analyze the influencing factors associated with these different types, providing a reference for developing intervention programs aimed at enhancing self-management behaviors in stroke patients.Methods:This study adopted a cross-sectional survey design. The stroke inpatients were selected through convenience sampling from the Department of Neurology at Huashan Hospital, Fudan University between October 2023 and August 2024. Data collection was conducted using the following instruments: the General Information Questionnaire, Stroke Self-Management Behavior Rating Scale, Self-Efficacy for Managing Chronic Disease 6-Item Scale, Stroke Health Knowledge Questionnaire, Social Support Rating Scale, Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, and the modified Rankin Scale. Stroke patients' self-management behaviors were categorized using systematic cluster analysis, and disordered multi-class Logistic regression was employed to identify the influencing factors associated with each category.Results:Finally, 210 stroke patients were enrolled, there were 148 males and 62 females, aged (60.82 ± 13.05) years. The total score of self-management behavior in stroke patients was (144.18 ± 23.24) points, with a score rate of 56.54%. Systematic cluster analysis identified four distinct self-management behaviors patterns: consistent implementers (25.71%, 54/210); unrealistically optimistic(54.76%, 115/210); optimistically proactive (13.81%, 29/210); and passive and resigned (5.71%, 12/210). Disordered multi-class Logistic regression analysis indicated that higher scores in stroke-related health knowledge were associated with a greater likelihood of being categorized as stable practice type and optimistic proactive type ( OR=1.130, 1.254, both P<0.05). Conversely, increased levels of depression correlate with a higher probability of being classified as passive waiting type ( OR=0.684, 0.722, 0.540, all P<0.05). Additionally, lower modified Rankin Scale scores were linked to an increased tendency to fall into the categories of stable practice type and blind optimism type ( OR=19.759, 23.148, both P<0.05). Conclusions:The self-management behaviors of stroke patients are generally suboptimal and exhibited distinct classification features. Significant differences are observed in stroke health knowledge, depression, and the modified Rankin Scale scores among the four patient types. Healthcare professionals should tailor intervention measures to the characteristics of each type to enhance patients' self-management capacity.

Objective:To explore the types and characteristics of self-management behaviors among stroke patients, as well as to analyze the influencing factors associated with these different types, providing a reference for developing intervention programs aimed at enhancing self-management behaviors in stroke patients.Methods:This study adopted a cross-sectional survey design. The stroke inpatients were selected through convenience sampling from the Department of Neurology at Huashan Hospital, Fudan University between October 2023 and August 2024. Data collection was conducted using the following instruments: the General Information Questionnaire, Stroke Self-Management Behavior Rating Scale, Self-Efficacy for Managing Chronic Disease 6-Item Scale, Stroke Health Knowledge Questionnaire, Social Support Rating Scale, Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, and the modified Rankin Scale. Stroke patients' self-management behaviors were categorized using systematic cluster analysis, and disordered multi-class Logistic regression was employed to identify the influencing factors associated with each category.Results:Finally, 210 stroke patients were enrolled, there were 148 males and 62 females, aged (60.82 ± 13.05) years. The total score of self-management behavior in stroke patients was (144.18 ± 23.24) points, with a score rate of 56.54%. Systematic cluster analysis identified four distinct self-management behaviors patterns: consistent implementers (25.71%, 54/210); unrealistically optimistic(54.76%, 115/210); optimistically proactive (13.81%, 29/210); and passive and resigned (5.71%, 12/210). Disordered multi-class Logistic regression analysis indicated that higher scores in stroke-related health knowledge were associated with a greater likelihood of being categorized as stable practice type and optimistic proactive type ( OR=1.130, 1.254, both P<0.05). Conversely, increased levels of depression correlate with a higher probability of being classified as passive waiting type ( OR=0.684, 0.722, 0.540, all P<0.05). Additionally, lower modified Rankin Scale scores were linked to an increased tendency to fall into the categories of stable practice type and blind optimism type ( OR=19.759, 23.148, both P<0.05). Conclusions:The self-management behaviors of stroke patients are generally suboptimal and exhibited distinct classification features. Significant differences are observed in stroke health knowledge, depression, and the modified Rankin Scale scores among the four patient types. Healthcare professionals should tailor intervention measures to the characteristics of each type to enhance patients' self-management capacity.

Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.

Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

OBJECTIVE To investigate the protective effect of artesunate(Art)against apoptosis and mitophagy induced by NaF in osteocytes MLO-Y4,and to explore the molecular mechanism.METHODS MLO-Y4 cells were treated with NaF(2 mmol·L-1)for 48 h to establish an in vitro model of osteocytes injuries,and the cells were divided into the cell control group,NaF(2 mmol·L-1)group and NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups.The cells were pretreated for 2 h and NaF was added for 48 h.The cell survival of MLO-Y4 cells was detected by MTT assay.The cell viability of MLO-Y4 cells was measured by Calcein-AM staining.The lactate dehydrogenase(LDH)content in the supernatant was examined by the LDH detection kit.The level of intracellular reactive oxygen species(ROS)was examined by DCFH-DA staining.The malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were detected by chemical colorimetry.Apoptosis was measured by Hoechst33342 staining and Annexin-V/PI staining.The level of mitochondrial membrane potential(MMP)was measured by JC-1 staining.The formation of autophagic vacuoles and morphological mitochondrial changes were observed via Lyso-tracker staining and Mito-Tracker staining.The ATP content was detected with the luciferase method.The expression of microtubule-associated protein light chain 3(LC-3)in mitochon-dria was examined by immunofluorescence staining.Protein expressions of LC-3,P62,E3 ubiquitin-ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)were detected by Western blotting.RESULTS Compared with the cell control group,the cell survival rate and cell viability were significantly reduced in the NaF group(P<0.01),LDH content in the supernatant,the level of intracellular ROS,the MDA content,apoptosis rate and autophagic vesicle formation were remarkably increased(P<0.01),protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly upregulated along with the elevation of LC-3 in damaged mitochondria(P<0.01),while P62 levels,SOD activity,MMP and ATP contents were reduced in NaF cells(P<0.05,P<0.01).Compared with NaF group,the cell viability and survival rate of MLO-Y4 cells in NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups were significantly increased(P<0.01);the content of LDH in supernatants was decreased obviously(P<0.01);the levels of intracellular ROS and MDA content were markedly reduced(P<0.05,P<0.01);the apoptosis rate and autophagic vesicle formation were remarkably decreased(P<0.05,P<0.01);protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly down-regulated along with the accumulation of LC-3 in damaged mitochondria(P<0.01);MMP and ATP content were also reduced(P<0.05,P<0.01);while SOD activityand P62 levelwere significantly increased(P<0.05,P<0.01).CONCLU-SION Art has a protective effect against oxidative damage induced by NaF in MLO-Y4 cells,which might be related to the inhibition of apoptosis and mitophagy.

Objective:To investigate the expression of replication factor C5 (RFC5) in cervical cancer, and its effect on the prognosis and immune regulation as well as its related mechanism.Methods:RFC5 mRNA expression data and the clinical data of 280 cervical cancer patients were downloaded from the Cancer Genome Atlas (TCGA) database in May 2023. The difference of RFC5 mRNA expression between cervical cancer tissues and paracancerous normal tissues was compared and the expression of RFC5 mRNA in patients with different clinicopathological characteristics was analyzed. According to the median expression level of RFC5 mRNA in cancer tissues, 280 patients were divided into the high expression group and the low expression group. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison. Gene Expression Profiling Interactive Analysis (GEPIA) 2 online tool was used to verify the relationship between RFC5 gene expression and the prognosis of cervical cancer. Univariate and multivariate Cox proportional risk models were used to analyze the factors influencing the overall survival (OS) of patients with cervival cancer in TCGA database. LinkedOmics database was used to screen the co-differentially expressed genes (DEG) related to RFC5 in cervical cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genesand Genomes (KEGG) pathway enrichment analysis of DEG related to RFC5 were performed based on the DAVID database. Based on the Tumor Immune Estimation Resource (TIMER) database, the relationship between RFC5 expression and tumor infiltrating immune cells in cervival cancer was analyzed by using Spearman method. The relationship between RFC5 expression and immunomodulatory factors in cervical cancer was analyzed based on tumor-immune system interactions database (TISIDB). The expression of RFC5 protein in cervical cancer tissues was analyzed based on Human Protein Atlas (HPA) database. The expression of RFC5 in pan-cancer and its correlation with OS were analyzed based on GEPIA2 online tool.Results:In TCGA database, the relative expression level of RFC5 mRNA in cervical cancer tissues (277 cases) was higher than that in paracancerous normal tissues (3 cases), and the difference was statistically significant ( P < 0.001), while there were no significant differences in the relative expression level of RFC5 mRNA in cancer tissues of patients with different age, pathological type and clinical staging (all P > 0.05). The OS of cervival cancer patients in high RFC5 expression group (139 cases) was better than that of patients in low RFC5 expression group (138 cases), and the difference was statistically significant ( P = 0.027). GEPIA tool verification indicated that expression of RFC5 in cervical cancer and its relationship with OS showed the same results. GO and KEGG enrichment analysis showed that RFC5-related genes were mainly involved in DNA replication, cell cycle, Fanconi anemia, mismatch repair, base excision repair, nucleotide excision repair and other signaling pathways. Multivariate Cox regression analysis showed that age ≥ 65 years, clinical staging Ⅳ and the low expression of RFC5 were independent risk factors of poor OS in patients with cervical cancer (all P < 0.05). TIMER database analysis showed that the expression of RFC5 was positively correlated with tumor purity ( rho = 0.198, P < 0.001), while weakly correlated or not correlated with the infiltration levels of B cells ( rho = 0.062, P = 0.306), CD8 + T cells ( rho = 0.168, P = 0.005), CD4 + T cells ( rho = -0.049, P = 0.418), macrophages ( rho = 0.034, P = 0.577), neutrophils ( rho = 0.169, P = 0.005) and bone marrow dendritic cells ( rho = 0.026, P = 0.667). Analysis of TISIDB data showed that RFC5 expression was mostly negatively correlated with immunosuppressive factors and immunostimulatory factors. HPA database showed that the expression level of RFC5 in cervical cancer tissues was higher than that in normal cervical tissues. GEPIA online tool database analysis showed that RFC5 expression was up-regulated in a variety of malignant tumors. The OS of thymoma patients with high RFC5 expression was better than that of those with low RFC5 expression, while the OS of acute myeloid leukemia patients with high RFC5 expression was worse than those with low RFC5 expression, and the differences in OS were statistically significant (both P < 0.05). Conclusions:RFC5 is highly expressed in cervical cancer and its expression is associated with prognosis of patients with cervival cancer. Overexpression of RFC5 may inhibit the expression of immunomodulatory factors, and it may regulate the development and progression of cervical cancer through DNA replication, cell cycle, mismatch repair, base excision repair and other related pathways.