Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

Objective To investigate the impacts of ultrasound-guided stellate ganglion block(SGB)on hemodynamics and postoperative cognitive function in patients undergoing shoulder arthroscopic surgery.Methods From January 2024 to June 2024,120 patients undergoing shoulder arthroscopic surgery in our hospital were randomly assigned into general anesthesia group(n=60,implementing general anesthesia)and assisted SGB group(n=60,implementing ultrasound-guided SGB combined with general anesthesia).The intraoperative hemodynamics,postoperative stress status[serum cortisol(Cor)and interleukin-6(IL-6)],postoperative pain level[evaluated by visual analogue scale(VAS)score],postoperative biomarkers[serum matrix metalloproteinase-9(MMP-9)and neurospecific protein S-100β(S-100β)],and postoperative cognitive function[evaluated using the mini-mental state examination(MMSE)]were compared between the two groups.Results There was no statistically significant difference in intraoperative blood loss and surgical time between the two groups of patients(P>0.05).After induction of anesthesia(T1),the mean arterial pressure(MAP)and heart rate(HR)of the two groups of patients were significantly lower than when they entered the operating room(T0),the differences were statistically significant(P<0.05).The MAP and HR during the beginning of the surgery(T2),30 min after the start of the surgery(T3),and at the end of the surgery(T4)were higher than those at T0,the differences were statistically significant(P<0.05).While the MAP and HR in the assisted SGB group during T1,T2,T3 and T4 time points were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The VAS scores of the assisted SGB group were significantly lower than those of the general anesthesia group at 12 and 24 h after surgery,and the differences were statistically significant(P<0.05).The levels of serum Cor and IL-6 in the two groups at 12 and 24 h after surgery were higher than those at 1 d before surgery,but the levels of serum Cor and IL-6 in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The levels of serum MMP-9 and S-100β in the two groups at 24 and 72 h after surgery were higher than those at 1 d before surgery(P<0.05),but the levels of serum MMP-9 and S-100β in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The MMSE score of the two groups at 3 and 5 d after surgery were lower than those at 1 d before surgery,but the MMSE score of the assisted SGB group was higher than that of the general anesthesia group,the difference was statistically significant(P<0.05).Conclusion The implementation of ultrasound-guided SGB during shoulder arthroscopic surgery can maintain intraoperative hemodynamic stability,obviously alleviate postoperative stress and pain,obviously reduce serum MMP-9 and serum S-100β levels,and help alleviate postoperative cognitive dysfunction.It is worthy clinical application.

Objective To investigate the intracranial hemodynamic parameters with transcranial color-coded duplex sonography(TCCS)in elderly patients with acute ischemic stroke(AIS)after endovascular therapy,and analyze their association with functional outcomes.Methods A total of 360 elderly AIS patients undergoing endovascular therapy in our hospital from March 1,2020 to January 31,2024 were prospectively included,and according to the score of modified Rankin scale(mRS)at 90 d,they were divided into a poor function group(mRS score 3-6,145 cases)and good function group(mRS score≤2,215 cases).TCCS was conducted on all the patients in 12 h after endovascular therapy to evaluate intracranial blood flow status.Peak systolic velocity(PSV),end-diastolic velocity(EDV),mean blood flow velocity(MFV),pulsatility index(PI),MFV ratio and PSV ratio,adjusted PSV ratio and adjusted MFV ratio were recorded in all pa-tients.Receiver operator characteristic(ROC)curve analysis was employed to analyze the value of TCCS parameters in predicting poor functional outcomes,and the AUC values and cut-off values were also analyzed.Results The PSV ratio,MFV ratio,adjusted PSV ratio and adjusted MFV ra-tio were significantly higher in the poor function group than the good function group(P＜0.01).The predictive performance of PSV ratio and MFV ratio were not good enough for poor functional outcome in the AIS patients(AUC＜0.750),while the adjusted PSV ratio and adjusted MFV ratio showed better predictive performance(P＜0.01).Multivariate logistic regression analysis showed that NIHSS score at admission ≥14.00,ASPECT score at admission≥8.00,adjusted PSV ratio＞1.39 and adjusted MFV ratio＞1.40 were independent risk factors for poor functional outcomes in AIS patients(P＜0.01).ROC curve analysis indicated that combined NIHSS score at admission+ASPECT score at admission showed poor value in predicting poor functional outcome in the AIS(AUC=0.780,95％CI:0.734-0.822),the predictive performance of combination of above two scores+adjusted PSV ratio+adjusted MFV ratio was significantly improved(AUC=0.976,95％CI:0.955-0.989),with higher sensitivity and specificity(Z=8.261,P＜0.01).Conclusion Early TCCS detection in elderly AIS patients after endovascular treatment is an effective method for identifying poor functional outcomes at 90 d,with the advantages of non invasiveness and easy op-eration.And,better predictive performance is obtained when adjusted PSV ratio and adjusted MFV ratio are combined with conventional predictors.

Objective:To explore the clinical efficacy of olapalib in the treatment of platinum-sensitive recurrent breast cancer susceptibility gene (BRCA)-mutated ovarian cancer.Methods:The clinical data of 105 patients with platinum-sensitive recurrent BRCA-mutated ovarian cancer confirmed by pathology/imaging from October 2020 to March 2023 in Baoding Second Central Hospital were selected retrospectively, and they were divided into the control group (52 cases) and the experimental group (53 cases) according to the treatment methods. The control group was treated with a platinum-containing regimen, followed by olaparib at the end of the treatment. The experimental group was treated with olaparib. The recent clinical outcomes, tumour marker levels, ovarian cancer functional assessment of treatment questionnaire (FACT-O) score, cancer fatigue scale (CFS) score, and adverse reaction were compared between the two groups. The survival curve was drawn by Kaplan-Meier, and the prognosis was compared.Results:The overall response rate clinical in the experimental group was higher than that in the control group: 64.15%(34/53) vs.44.23%(23/52), there was a statistical difference ( χ2 = 4.20, P<0.05). After treatment, the levels of serum glycoantigen (CA) 125, CA153, human epithelial protein 4 (HE4), and vascular endothelial growth factor (VEGF) in the experimental group were lower than those in the control group: (42.35 ± 6.85) kU/L vs. (46.64 ± 7.11) kU/L, (24.26 ± 4.58) kU/L vs. (26.74 ± 5.20) kU/L, (144.25 ± 19.85) pmol/L vs. (155.64 ± 21.26) pmol/L, (335.32 ± 38.41) μg/L vs. (359.47 ± 41.24) μg/L; the FACT-O scores in the experimental group was higher than that in the control group: (55.24 ± 6.85)scores vs. (51.26 ± 7.19) scores; the CFS scores in the experimental group was lower than that in the control group: (38.51 ± 6.11) scores vs. (44.94 ± 8.38) scores, there were statistical differences ( P<0.05).After treatment, the rate of dizziness, nausea, leukopenia, neutropenia, thrombocytopenia, and anemia in the experimental group were lower than those in the control group ( P<0.05). The results of the survival curve showed that the median progression-free survival in the experimental group was longer than that in the control group ( P<0.05). Conclusions:Single-agent olaparib is effective in treating platinum-sensitive recurrent BRCA-mutated ovarian cancer, and can improve quality of life, reduce anemia and adverse reaction, and prolong patients′ median survival.

Objective To investigate the impacts of ultrasound-guided stellate ganglion block(SGB)on hemodynamics and postoperative cognitive function in patients undergoing shoulder arthroscopic surgery.Methods From January 2024 to June 2024,120 patients undergoing shoulder arthroscopic surgery in our hospital were randomly assigned into general anesthesia group(n=60,implementing general anesthesia)and assisted SGB group(n=60,implementing ultrasound-guided SGB combined with general anesthesia).The intraoperative hemodynamics,postoperative stress status[serum cortisol(Cor)and interleukin-6(IL-6)],postoperative pain level[evaluated by visual analogue scale(VAS)score],postoperative biomarkers[serum matrix metalloproteinase-9(MMP-9)and neurospecific protein S-100β(S-100β)],and postoperative cognitive function[evaluated using the mini-mental state examination(MMSE)]were compared between the two groups.Results There was no statistically significant difference in intraoperative blood loss and surgical time between the two groups of patients(P>0.05).After induction of anesthesia(T1),the mean arterial pressure(MAP)and heart rate(HR)of the two groups of patients were significantly lower than when they entered the operating room(T0),the differences were statistically significant(P<0.05).The MAP and HR during the beginning of the surgery(T2),30 min after the start of the surgery(T3),and at the end of the surgery(T4)were higher than those at T0,the differences were statistically significant(P<0.05).While the MAP and HR in the assisted SGB group during T1,T2,T3 and T4 time points were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The VAS scores of the assisted SGB group were significantly lower than those of the general anesthesia group at 12 and 24 h after surgery,and the differences were statistically significant(P<0.05).The levels of serum Cor and IL-6 in the two groups at 12 and 24 h after surgery were higher than those at 1 d before surgery,but the levels of serum Cor and IL-6 in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The levels of serum MMP-9 and S-100β in the two groups at 24 and 72 h after surgery were higher than those at 1 d before surgery(P<0.05),but the levels of serum MMP-9 and S-100β in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The MMSE score of the two groups at 3 and 5 d after surgery were lower than those at 1 d before surgery,but the MMSE score of the assisted SGB group was higher than that of the general anesthesia group,the difference was statistically significant(P<0.05).Conclusion The implementation of ultrasound-guided SGB during shoulder arthroscopic surgery can maintain intraoperative hemodynamic stability,obviously alleviate postoperative stress and pain,obviously reduce serum MMP-9 and serum S-100β levels,and help alleviate postoperative cognitive dysfunction.It is worthy clinical application.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective:To investigate the impact of minocycline on myocardial injury in diabetes cardiomyopathy(DCM)rats by regulating 5'-AMP activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator activator receptor gamma coactiva-tor 1α(PGC-1α)signal pathway.Methods:SD rats were fed with high-fat diet for 4 weeks,and then a single intraperitoneal injection of 35 mg/kg streptozotocin was used to induce the DCM model.They were randomly grouped into model group,low-dose minocycline(20 mg/kg)group,high-dose minocycline(40 mg/kg)group,high-dose minocycline+Dorsomorphin(AMPK inhibitor,0.2 mg/kg)group,with 12 rats in each group,another 12 normal rats were fed with normal feed for 4 weeks,and then were given a single intraper-itoneal injection of the same dose of citric acid buffer,which was set as a sham operation group,after the intervention with minocy-cline and Dorsomorphin,and the fasting blood glucose(FBG),total cholesterol(TC)and triglyceride(TG)were measured;left ven-tricular ejection fraction(LVEF)and left ventricular short axis shortening(FS)were measured by ultrasound;HE staining and Mas-son staining were applied to detect the pathological morphology of myocardial tissue of rats in each group;the levels of serum and myo-cardial tissue inflammation IL-6,IL-18,and myocardial tissue oxidative stress indicators-superoxide dismutase(SOD)and malondial-dehyde(MDA)were measured with the kit;Western blot was applied to detect the expression of AMPK/SIRT1/PGC-1α pathway pro-tein in myocardial tissue of rats in each group.Results:Compared with the sham operation group,the myocardial tissue in the model group was seriously damaged,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocar-dial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myocardial tissue were obviously increased(P<0.05),the levels of LVEF,FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were obviously decreased(P<0.05);compared with the model group,the myocardial tissue damage of rats in the low-dose and high-dose minocycline groups were reduced,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myocardial tissue were decreased(P<0.05),the LVEF,the levels of FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were increased(P<0.05);compared with the low-dose minocycline group,the myocardial tissue damage in the high-dose minocycline group was further reduced,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myo-cardial tissue were further decreased(P<0.05),the levels of LVEF,FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were further increased(P<0.05);compared with the high-dose minocycline group,the myocar-dial tissue damage of rats in the high-dose minocycline+Dorsomorphin group increased,the levels of FBG,TC and TG,the cross-sec-tional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tis-sue,and the level of MDA in myocardial tissue were increased(P<0.05),the LVEF,the levels of FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were decreased(P<0.05).Conclusion:Minocycline can reduce oxidative stress and inflammation in DCM rats by activating AMPK/SIRT1/PGC-1α signal,and improve glycolipid metabolism,thereby reducing myocardial injury and repairing cardiac function in rats.

Objective:To systematically review qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy, and to gain insights into the initiation, development, and effects of these symptoms, along with their implications for patients, to guide the creation of targeted strategies for symptom management.Methods:The qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy were performed across several databases, which included the Cochrane Library, Joanna Briggs Institute Evidence based Healthcare Center Database, PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, Wanfang Data, and Chinese Biomedical Literature Database. The retrieval period was from the establishment of the database to April 30, 2024. The studies' quality was evaluated utilizing the iteration of the Joanna Briggs Institute Qualitative Assessment and Review Instrument designed for qualitative research. Data synthesis was carried out using Meta-aggregation techniques.Results:A total of 15 articles were included and 41 results were extracted, which were grouped into 11 new categories and integrated into 3 primary themes: the manifestation of bone and joint symptoms was highly unique and varied, prominently featuring experiences such as migratory joint pain, morning stiffness, and cramps affecting both large and small joints, frequently associated with functional limitations; these symptoms significantly influence patients' everyday activities and mental health, contributing to feelings of anxiety, avoidance behaviors, fear, and a reduction in overall quality of life; to manage the intricate nature of their symptoms, patients employ a variety of coping mechanisms, such as engaging in physical activity, taking dietary supplements, consulting about medications, and seeking support from external sources.Conclusions:During endocrine therapy for breast cancer, patients exhibit diverse characteristics of musculoskeletal symptoms, and the resulting fear of recurrence, avoidance behaviors, and anxiety have a negative impact on their psychological well-being and overall health. Healthcare professionals should take into account individual differences, such as age, menopausal status, type of endocrine therapy, medication adherence, and factors that may exacerbate or alleviate symptoms, in order to effectively predict, assess, and manage bone and joint symptoms during endocrine therapy.

Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.