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 integrate the best evidence of non drug intervention for blood lipid management of breast cancer survivors used the evidence-based method, and provide evidence-based evidence for clinical medical staff to carry out dynamic monitoring and management of blood lipid abnormalities.Methods:According to the 6S model, the evidence summary, clinical decision, recommended practice, guidelines, systematic review, expert consensus, scientific position statement and other non-drug interventions on lipid management of breast cancer survivors were systematically searched from the evidence-based guidelines website and related databases from database establishment until June 10, 2024. The quality of the included literature was evaluated, and the evidence was extracted, summarized and formed.Results:A total of 14 literatures were included, including 7 guidelines, 5 expert consensus and 2 systematic reviews. Totally 21 best evidences were collected from the necessity of lipid management, lipid management objectives, individualized lipid monitoring and lipid management strategies.Conclusions:The quality and level of the best evidence collected in this study are generally high, which has reference significance for clinical medical staff to carry out scientific and effective non drug intervention in lipid management of breast cancer survivors. In the evidence transformation stage, it is necessary to fully consider the individual differences of patients, in order to improve the intervention effect and the quality of life of patients.

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: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

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.

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.