Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective To investigate the antitumor effects of triptolide against CT26 colon cancer and its impact on the expression of Polo-like kinase-1(PLK-1)protein.Methods Forty clean grade BALB/c mice,each mouse was implanted with 1×106 CT26 cells into the dorsal side of the right forelimb to establish a tumor-bearing mouse model.Experimental animals were randomly divided into four groups,the tumor model group(saline control),the positive drug group[oxaliplatin,5 mg/(kg·d)],the low-dose triptolide group[50 μg/(kg·/d)],and the high-dose triptolide group[100 μg/(kg·d)].The drugs were administered through intraperitoneal injection(10 times in total,once every other day).The in vitro effects of the drugs on the proliferation,migration,invasion,and mitosis of CT26 cells were also assessed.Results Triptolide significantly inhibited the proliferation,migration,and invasion of CT26 colon cancer cells,and disrupted the separation of centrosomes and the correct arrangement of chromosomes during the prophase of mitosis in tumor cells.The binding energy of triptolide and PLK-1 protein was-7.1 kcal/mol,and it could down-regulate the expression of PLK-1 in CT26 cells.Conclusion Triptolide exerts its antitumor effects against CT26 colon cancer by downregulating the expression of PLK-1.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To assess the safety,efficacy and potential impact of stem cell therapy(SCT)in improving erectile dys-function(ED).Methods:A comprehensive search strategy was used to search the literatures on safety and efficacy evaluation of stem cell(SC)in the treatment of ED by human clinical trials from PubMed,Embase and Web of science databases with a search time frame from database creation to July 4,2024.The exclusion criteria were as follows:reviews,conference abstracts,animal experi-ments,and duplicate sample literature.Results:The study initially screened 1 773 papers,and 17 were included in the final analy-sis.These studies involved a total of 269 ED patients,and a variety of sources of stem cells had been used in the treatment of ED,in-cluding adipose-derived stem cells,bone marrow-derived stem cells,placental stroma-derived stem cells,umbilical cord-derived stem cells,dental pulp-derived stem cells,and oral mucosa-derived stem cells.All studies were conducted by injecting stem cells into the cavernous body of the penis,but there is no fixed standard for the amount of injection,injection site and number of injections.The op-timal treatment mode was still being explored.Patients' International Index of Erectile Function(IIEF)scores and Erection Hardness Score(EHS),peak systolic velocity(PSV),and end diastolic velocity(EDV)improved after treatment.But some studies showed that the efficacy of the treatment diminished with increasing time.No serious adverse effects were reported in any of the studies and none of the adverse effects persisted for a long period of time.The most common adverse effects included injection site reactions,and SCT showed a good safety and tolerability profile.Conclusion:SCT has the potential to be a promising and innovative regenerative therapy option for ED patients.In the future,with the advancement of stem cell technology,larger randomized controlled studies should continue to be conducted to explore standardized treatments,so as to further evaluate the long-term efficacy and safety of SCT for ED.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Objective:To analyze the correlation of monocyte/high density lipoprotein ratio(MHR),neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR)and bone density,bone metabolism markers in elderly essential hypertension with osteoporosis(OP)patients.Methods:This study was a retrospective study,198 elderly essential hypertension patients who were admitted in our hospital from January 2022 to June 2024 were selected.According to the patient's bone mass test results,patients were divided into normal bone mass group(n=79),osteopenia group(n=68)and OP group(n=51).MHR,NLR,PLR,bone density(left hip,left femoral neck and lumbar spine L1-L4)and bone metabolism markers were compared among three groups,the correlation of MHR,NLR,PLR and bone density,bone metabolism markers were analyzed by Pearson correlation.Results:MHR,NLR,PLR in normal bone mass group,osteopenia group and OP group increased in turn(P＜0.05).The left hip,left femoral neck and lumbar spine L1-L4 bone density in normal bone mass group,osteopenia group,OP group decreased in turn(P＜0.05).25-hydroxyvitamin D[25(OH)D]in normal bone mass group,osteopenia group and OP group decreased in turn,alkaline phosphatase(ALP)and parathyroid hormone(PTH)increased in turn(P＜0.05).MHR,NLR and PLR were negatively correlated with left hip bone density,left femoral neck bone density,lumbar spine L1-L4 bone density,25(OH)D and positively correlated with PTH and ALP(P＜0.05).Conclusion:The increase of MHR,NLR and PLR in elderly essential hypertension with OP patients can affect bone mineral density and bone metabolism.

Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.

Inflammatory response,immunosuppression,and drug sensitivity have been reported to have a significant correlation with the disulfidptosis levels in cancer patients.However,the value of disulfidpto-sis in colorectal cancer therapy remains unclear.Therefore,we classified the CRC cells into different cell types using single-cell sequencing data and cell-specific markers and analyzed their relationship with the cell disulfidptosis level.We found that the high disulfidptosis regions were concentrated in epithelial-like CRC cells.Further exploration using the disulfidptosis and programmed cell death 1 inhibitor therapy treated differential expression genes indicated that CRC patients with high disulfidptosis levels exhibited a lower risk profile and increased sensitivity to immunotherapy.By using the spatial transcriptomic analy-sis,we found that ubiquinol-cytochrome c reductase core protein 1(UQCRC1),a disulfidptosis-related gene,is highly expressed in epithelial-like CRC cells and co-localized with immune-infiltrated tumor re-gions.Additional bioinformatic analyses and experimental validation further confirmed that UQCRC1 was downregulated in CRC tissues.Overexpression of UQCRC1 suppressed CRC cell proliferation and migra-tion.These findings indicate that UQCRC1 is a potential target for CRC diagnosis and treatment.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*