Objective:To investigate the role of heat shock transcription factor 1(HSF1)in hepatitis B virus X protein(HBx)-driven migration and invasion of hepatocellular carcinoma(HCC)cells,and to preliminarily explore the mechanism of HSF1 mediating HBx-driven HCC progression.Methods:4D label-free quantitative proteomics and Western blot were used to analyze the effect of HBx on HSF1 expression.HBx was overexpressed in the HCC cell lines Huh7 and MHCC97H,and its impact on the mRNA and protein levels and stability of HSF1 was assessed by RT-PCR and Western blot.The Cancer Genome Atlas database was used to analyze the expres-sion of HSF1 in hepatitis B virus(HBV)-associated HCC tissues and its relationship with tumor stage/grade and patient prognosis,and Western blot was used to measure the expression of HSF1 in HBV-associated HCC tissues.HBx was overexpressed in HCC cells,fol-lowed by HSF1 knockdown or cell treatment with the HSF1 inhibitor KRIBB11,and Transwell migration and invasion assay,scratch as-say,and F-actin staining experiment were performed to analyze the role of HSF1 in HBx-driven HCC cell migration and invasion.GEO and HCMDB datasets were used to identify the downstream target of HSF1,and the role of downstream target c-Myb in HSF1-me-diated HBx-driven HCC progression.Results:HBx upregulated HSF1 protein levels without significantly affecting its mRNA expres-sion,through enhancing HSF1 protein stability.HSF1 was highly ex-pressed in HBV-associated HCC tissues,and its elevated expres-sion correlated with tumor stage/grade and poor prognosis.HBx overexpression significantly promoted the migration,invasion,wound-healing capacity,and pseudopodia formation capacity of Huh7 and MHCC97H cells,while HSF1 knockdown or KRIBB11 treatment significantly attenuated the HBx-driven migration and in-vasion of HCC.HSF1 promoted the expression of the metastasis-associated protein c-Myb,and c-Myb overexpression in HSF1-knock-down HCC cells restored the promotive effect of HBx on HCC cell migration and invasion.Conclusion:HBx enhances HSF1 protein stability to promote its expression.Upregulation of c-Myb by HSF1 plays a pivotal role in HBx-driven HCC cell migration and inva-sion.Targeting HSF1 may help to delay the progression of HBV-associated HCC.

Objective To explore the histological and immunohistochemical characteristics of undifferentiated liver cancer in small tissue biopsy specimens.Methods Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)was used to obtain liver tissue strips and cell samples.The tissue and cell morphology of a case of liver undifferentiated carcinoma were analyzed by hematoxylin-eosin staining,immunohistochemical staining,and cell smear techniques.The related literatures of undifferentiated liver cancer were retrieved from PubMed and Wanfang databases to summarize the diagnostic criteria of undifferentiated liver cancer.Results Histologically,this case of undifferentiated liver cancer presented as a patchy arrangement of oval or spindle shaped tumor cells,with large,deeply stained,and distinctly atypical anaplastic cells visible in between.Localized nuclear fission images could be observed.The cytological manifestation was nuclear atypical cells,with less cytoplasm in atypical cells,and some cells had red staining of cytoplasm resembling squamous cell carcinoma cytoplasm.The immunohistochemical results showed epithelial membrane antigen(EMA)(+),cytokeratin(CK)18(+),glutamine synthetase(GS)(-),carbohydrate antigen 19-9(CA19-9)(-),vimentin(-),CK7(-),CK20(-),alpha fetoprotein(AFP)(-),glypican 3(Gpc-3)(-),hepatocellular paraffin antigen-1(Hep-1)(-),and chromogranin A(CgA)(-).The results of literature review showed that undifferentiated liver cancer was more common in middle-aged and elderly men,and generally appeared as isolated circular nodules.In 8 out of 9 cases,tumor cells were observed to grow diffusely under the microscope,and no typical glandular or beam like growth patterns of liver tumors were observed.The malignant degree of tumor cells was high,with 5 out of 9 cases showing significantly atypical interstitial cells.Immunohistochemical features included positive expression of epithelial derived markers(such as pan cytokeratin[CKpan],EMA,and CK18)and negative expression of liver derived markers(AFP,Hep-1,Gpc-3,and arginase-1),which might be accompanied by positive expression of neuroendocrine markers.Conclusion The histological morphology of undifferentiated liver cancer is characterized by diffuse distribution of anaplastic cells,without any glandular or cord like arrangement.The tumor often expresses epithelial derived markers,while liver derived markers show negative expression.

Objective:To analyze the related factors of membranous urethral length in patients with benign prostatic hyperplasia (BPH) and the early recovery of urinary control function after Holmium laser enucleation of the prostate (HoLEP).Methods:A retrospective study was conducted to analyze the case data of 124 patients with BPH admitted to the Yan′an University Affiliated Hospital from January 2017 to January 2023. According to the recovery of postoperative urinary control function, the patients were divided into the urinary control group ( n=81) and the urinary incontinence group ( n=43). The clinical data of the two groups of patients were collected, including age, body mass index, comorbidities, etc. The perioperative indicators [including prostate volume, prostatic specific antigen, membranous urethral length, international prostate symptom score (IPSS), maximum bladder capacity, degree of prostate protrusion into the bladder, etc.], the urodynamic indicators before the operation and 6 months after the operation (including maximum urine flow rate, maximum urethral pressure and bladder compliance) and the urinary control situation of the two groups of patients were observed. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as the cases and percentage, and Chi-square test was used for comparison between groups. Univariate and multivariate Logistic regression analysis were used to evaluate the influencing factors of early urinary control function recovery after HoLEP. Results:All patients successfully completed the surgery, and the follow-up was conducted 6 months after the operation as the time point. The results of univariate analysis showed that there were no statistically significant differences in age, body mass index, comorbidities, prostatic specific antigen, IPSS score and the degree of prostate protrusion into the bladder between the urinary control group and the urinary incontinence group ( P>0.05). The operation time, indwelling catheter time, prostate volume, preoperative membranous urethral length, postoperative membranous urethral length and the postoperative maximum bladder capacity of the two groups of patients all showed statistically significant differences ( P<0.05). Before the operation, there were no statistically significant differences in urodynamic indicators such as maximum urinary flow rate, maximum urethral pressure and bladder compliance between the two groups of patients ( P>0.05). Six months after the operation, the maximum urinary flow rate, the maximum urethral pressure and the bladder compliance in the two groups of patients increased compared with those before the operation. Moreover, the maximum urinary flow rate [(10.48±0.65) mL/s vs (9.41±0.53) mL/s], the maximum urethral pressure [(41.25±3.46) cmH 2O vs (38.21±3.16) cmH 2O], and bladder compliance [(32.23±3.13) cmH 2O vs (30.23±2.35) cmH 2O] were higher than those in the urinary incontinence group, and the differences were statistically significant ( P<0.05). The results of multivariate Logistic regression analysis showed that operation time ≥1 h, indwelling catheter time ≥5 d, prostate volume ≥60 mL, preoperative membranous urethral length <14 mm, and postoperative membranous urethral length <13 mm were independent risk factors for the recovery of early urinary control function after HoLEP ( OR>1, P<0.05), the maximum bladder capacity after surgery was an independent protective factor for the recovery of early postoperative urinary control function ( OR<1, P<0.05). Conclusions:Preoperative membranous urethral length <14 mm and postoperative membranous urethral length <13 mm are risk factors affecting the recovery of early urinary control function after HoLEP in patients with BPH. A longer membranous urethral length can reduce the risk of postoperative complications and accelerate the recovery of urinary control function in patients.

Objective To explore the facilitators and barriers of palliative care volunteering,and to provide references for further advancement of palliative care volunteering.Methods Purposeful sampling was used to select 12 volunteers from a palliative care ward in Hangzhou,Zhejiang Province,between April and September 2024.Semi-structured interviews were conducted,and directed content analysis was applied to organize and analyze the data,followed by theme analysis.Results Facilitators and barriers for volunteers' participation in palliative care volunteering were extracted.The 5 sub-themes of facilitators include motivating factors and perceived benefits,support and collaboration among volunteers,professional training and healthcare recognition,increased social awareness and public acceptance,and government support and institutional safeguards.The 5 sub-themes of barriers include limitations in individual capacity,challenges in collaboration with patients,families and healthcare workers,inadequate management and service mechanisms,uneven development of palliative care and insufficient public attention to psychological problems,and inadequate relevant laws and incentives.Conclusion There are more factors affecting the development of palliative care volunteering,and healthcare professionals should adopt targeted strategies to promote the active participation of volunteers in order to promote the sustainable development of palliative care volunteering.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Background: Epimedii Folium is well known for its medicinal value. Four Epimedium species—Euphorbia brevicornu, E. sagittatum, E. pubescens, and E. koreanum—are the designated original plants of Epimedii Folium. Objective: The objective of this study is to facilitate the identification of the four Epimedium species and clarify their distributional responses to climate change. Methods: In this study, we assessed the genetic divergence of the four species and identified the molecular markers for species identification by using chloroplast genome sequences. Furthermore, we forecasted the distribution of potentially suitable regions of the four species Folium under climate change. Results: The authors obtained 26 chloroplast genome sequences of the four species and identified 1393 variable sites and 273 indel events. Genetic divergence analyses revealed that E. koreanum had long genetic distance from the other three species. Compared with the complete chloroplast genome, six hypervariable markers were discovered, and both rps4-trnL and ndhF were chosen as Epimedii Folium-specific DNA barcodes. Climate change is expected to influence the geographical distribution of the four Epimedium species, which were primarily found in China, South Korea, and Japan, leading to both expansion and contraction of their distribution ranges. Conclusion: Two identification markers were selected as the specific DNA barcodes for all four original plant species of Epimedii Folium. In addition, the shift of potential suitable area in various climate scenarios has been predicted. With the support of identification markers and the dynamics of suitable distribution areas, we are able to establish a foundation for the sustainable utilization of medicinal Epimedium resources in the future.

A 70-year-old female patient with tumor in the neck and body of the pancreas received 11 cycles of chemotherapy with paclitaxel and gemcitabine. Due to disease progression, she subsequently underwent chemotherapy of fluorouracil, calcium folinate, and irinotecan, combined with immunotherapy of serplulimab. After 28 days (only one session of immunotherapy), the patient developed drooping of the right upper eyelid and chest tightness, followed by pain in the middle and lower segments of the sternum and radiating pain to the throat, accompanied by speech difficulties, dysphagia, and chest tightness and wheezing. Laboratory tests indicated hypersensitive troponin T 0.551 μg/L, creatine kinase (CK) 3 426 U/L, CK-MB 176 μg/L, and myoglobin 1 702 μg/L. The imaging examination of head and neck ruled out intracranial lesions, while the electrocardiogram suggested myocardial damage. Immune-related myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) induced by serplulimab was considered. Immunotherapy was temporarily halted, and treatments with methyprednisolone and human immunoglobulin were administered. Sixteen days later, clinical symptoms of IM3OS in the patient were improved, with laboratory tests showing hypersensitive troponin I 0.075 μg/L, CK 216 U/L, CK-MB 58 μg/L, and myoglobin 273 μg/L. Upon follow-up, the patient switched to monotherapy with irinotecan alone or combined with raltitrexed for cancer treatment, clinical symptoms of IM3OS did not recur, and no abnormalities were observed in myocardial injury markers or muscle enzymes.

Objective:To investigate the operation of water improvement projects in villages affected by drinking-water-borne endemic arsenic poisoning in Shaanxi Province, the arsenic level in both internal and external environments, the trend of disease development and patient management, and evaluate the effectiveness of prevention and control measures.Methods:From March to December 2023, in accordance with the requirements of the "Notice of the Office of Shaanxi Provincial Health Commission on Issuing the Monitoring Plan for Key Endemic Diseases such as Kashin-Beck Disease" and the "Monitoring Plan for Endemic Fluorosis and Arsenism in Shaanxi Province", all villages affected by drinking-water-borne arsenic disease were monitored. Water arsenic testing was carried out in accordance with the "Standard Test Methods for Drinking Water Inorganic Nonmetallic Indicators" (GB/T 5750.5-2006), and the evaluation of whether water arsenic exceeded the standard was conducted based on the "Sanitary Standards for Drinking Water" (GB 5749-2022). According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the arsenic poisoning status of all population in the disease affected areas was investigated. In 5 villages of 3 monitoring counties, 358 people were randomly selected to determine the urinary arsenic level, and the determination was made according to the "Safety Guideline Value of Urinary Arsenic for Human Population" (WS/T 665-2019). According to the "Notice of the National Health Commission on Issuing the Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)", elimination evaluation was conducted.Results:A total of 2 cities, 3 counties, 9 towns, and 13 endemic villages were monitored, with a water improvement rate of 100% (13/13), and all were operating normally. The arsenic level in residents' drinking water was < 0.01 mg/L. A total of 12 688 people were examined, and 338 cases of arsenic poisoning were detected, all of whom were historical cases. There were no new cases of arsenic poisoning or skin cancer patients. The geometric mean of urinary arsenic was 0.026 0 mg/L, which was lower than the safety guideline value of 0.032 mg/L for urinary arsenic in the population. All 338 existing arsenic poisoning patients had received family doctor contract services and implemented follow-up management. The drinking-water-borne endemic arsenic poisoning areas counties in Shaanxi Province have reached the elimination standard.Conclusions:The water improvement project in drinking-water-borne endemic arsenic poisoning areas in Shaanxi Province is operating normally. The arsenic content in both the internal and external environments of the population meets the standard. The condition is stable and no new cases have been detected. Follow up management has been implemented for all current cases. All affected counties have reached the elimination standard.

Objective:To investigate the association between blood pressure variability (BPV) and all-cause mortality and cardiovascular events in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and provide reference for clinical management in CAPD patients.Methods:This retrospective cohort study included patients who received CAPD at Guangdong Provincial People's Hospital between May 1, 2010, and July 31, 2023. Baseline and clinical data of the patients were collected. Coefficient of variation of systolic blood pressure (CVSBP) was used to assess BPV. The patients were divided into CVSBP T1, CVSBP T2 and CVSBP T3 groups based on CVSBP tertiles, and the differences among the three groups were compared. Diastolic blood pressure and mean arterial pressure were used to further assess BPV and sensitivity analysis was conducted. The primary endpoint was the composite outcome of all-cause mortality and cardiovascular events. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the association between CVSBP and the primary endpoint.Results:A total of 358 CAPD patients were included, with age of (43.6±13.3) years, and 197 males (55.0%). The proportion of males, proportion of smoking, baseline blood urea nitrogen, serum creatinine and serum albumin in CVSBP T2 (9.08%≤CVSBP<12.55%, n=120) group and CVSBP T3 (CVSBP≥12.55%, n=119) group were lower than those in CVSBP T1 group (CVSBP<9.08%, n=119), and baseline systolic blood pressure, residual kidney Kt/V and total Kt/V were higher than those in CVSBP T1 group, with statistically significant difference among the three groups (all P<0.05). During follow-up of 37(23, 76) months, 49 patients (13.7%) experienced the composite endpoint events, including 12 patients (3.4%) of all-cause deaths and 42 patients (11.7%) of cardiovascular events. Kaplan-Meier survival analysis showed that the incidence of composite endpoint events in CVSBP T3 group was higher than that in CVSBP T1 group and CVSBP T2 group, but the difference was not statistically significant (Log-rank χ2=3.795, P=0.150). Multivariate Cox regression analysis showed that, after adjusting for age, sex, diabetes, baseline systolic blood pressure, residual renal function, and serum albumin, as a continuous variable, CVSBP was not associated with the risk of composite outcome in CAPD patients ( HR=1.058, 95% CI 0.985?1.135, P=0.122); as a categorical variable, with CVSBP T1 group as reference, CVSBP T2 group and CVSBP T3 group were not associated with the risk of composite outcome ( HR=1.222, 95% CI 0.471?3.167, P=0.681; HR=1.827, 95% CI 0.737?4.530, P=0.193). The sensitivity analysis showed that increased variability of diastolic blood pressure ( HR=1.162, 95% CI 1.063?1.270, P=0.021) and increased variability of mean arterial pressure ( HR=1.114, 95% CI 1.030?1.204, P=0.007) were correlated with higher risk of composite outcome in CPAD patients. Conclusions:Systolic blood pressure variability during follow-up is not associated with risk of composite outcome of all-cause mortality and cardiovascular events in CAPD patients. Increased variability of diastolic blood pressure and increased variability of mean arterial pressure are associated with a higher risk of composite outcome in CPAD patients. Interventions to reduce BPV may be helpful to improve the long-term prognosis of CAPD patients.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.