To report diagnosis and treatment of a patient with rectal cancer and synchronous liver metastases, accompanied by severe coronary artery stenosis and cardiac insufficiency, and to provide a reference for clinical decision-making in such cases through introducing the treatment contradiction, the choice of systemic treatment plan and the timing of operation, and the final outcome. After definitive diagnosis, the patient received systemic therapy with cetuximab＋irinotecan＋oxaliplatin＋raltitrexed, and along with oral medication to improve cardiac function, followed by elective coronary revascularization. After revascularization, the cardiac function of patient was fully improved. And the tumor lesion was effectively controlled after antitumor therapy. Once the cardiac condition of patient stabilized, two-stage surgical resection of the primary rectal cancer and liver metastases was performed, ultimately achieving tumor-free status, and discharged.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

ObjectiveTo explore the distribution and evolution patterns of traditional Chinese medicine （TCM） syndromes and syndrome elements in psoriasis vulgaris （PV）. MethodsLiterature related to TCM syndromes of PV published in databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform （Wanfang）， VIP Chinese Technology Periodical Database （VIP）， Chinese Biomedical Literature Database （CBM）， PubMed， Embase， and Web of Science from their inception to December 31， 2023， was retrieved. Statistical analysis was conducted on the distribution of TCM syndromes and syndrome elements in the included studies. The data were further categorized into five-year periods to analyze the dynamic changes in syndromes and syndrome elements over time. ResultsA total of 2,853 studies were included， with 5,896 syndrome occurrences. The most common TCM syndromes in PV were blood-heat syndrome （2,167 occurrences， 36.75%）， blood-stasis syndrome （1,219 occurrences， 20.68%）， blood-dryness syndrome （1,124 occurrences， 19.06%）， and damp-heat syndrome （263 occurrences， 4.46%）. The most frequent syndrome categories included blood syndromes （4,680 occurrences， 79.38%） and dampness syndromes （347 occurrences， 5.89%）. The most common syndrome elements related to disease location were blood division （4,874 occurrences， 94.38%） and spleen （99 occurrences， 1.92%）. The most common syndrome elements related to disease nature were blood-heat （2,213 occurrences， 25.96%）， blood-dryness （1,434 occurrences， 16.82%）， and blood-stasis （1,330 occurrences， 15.60%）. Except for the period 1978-1983， blood-heat， blood-stasis， and blood-dryness syndromes consistently ranked among the top three， with their combined proportion showing an overall upward trend （from 67.65% to 81.69%）. The proportion of spleen deficiency with damp obstruction syndrome also increased （from 0.24% to 1.46%）. In terms of syndrome classification， the proportion of blood syndromes showed an overall upward trend （from 67.65% to 83.46%）， ranking first in all periods. The proportion of dampness syndromes showed a general downward trend （from 17.65% to 4.54%）， ranking second after blood syndromes in most periods except for 1994-1998 and 1999-2003. The proportion of spleen-related syndromes showed an overall increase （from 0.24% to 1.85%）. Regarding disease location elements， the proportion of blood division remained stable above 90%， while the proportion of spleen involvement increased （from 0.68% to 3.23%）. As for disease nature elements， blood-heat （from 19.23% to 33.27%） and blood-stasis （from 1.92% to 20.83%） significantly increased， while dampness initially decreased and then slightly increased （from 11.54% to 5.73%）. ConclusionIn the distribution of PV-related TCM syndromes， blood-heat， blood-stasis， and blood-dryness syndromes are the most common. Blood syndromes dominate syndrome classification， with disease location primarily in the blood division and disease nature characterized by blood-heat， blood-stasis， and blood-dryness. Evolutionary trends indicate that blood-heat， blood-stasis， and blood-dryness syndromes remain predominant and are increasing in proportion， while spleen deficiency with damp obstruction syndrome is also rising. Among syndrome classifications， the proportion of blood syndromes is increasing， dampness syndromes are decreasing， and spleen-related syndromes are on the rise. In terms of syndrome elements， blood division remains dominant， while spleen involvement is increasing. The proportion of blood-heat and blood-stasis is significantly increasing， while dampness first declines and then slightly rebounds. Overall， the mainstream TCM perspective of treating PV based on blood differentiation remains unchanged， with syndrome distribution focusing on blood division. The increasing importance of spleen deficiency and dampness in disease pathogenesis represents a new trend.

Cuproptosis and ferroptosis， two recently identified metal ion-dependent forms of cell death， are triggered by homeostasis dysregulation of intracellular copper and iron， as well as oxidative stress. They demonstrate considerable potential in anti-tumor therapy. Cuproptosis arises from mitochondrial dysfunction and proteotoxic stress caused by copper overload， while ferroptosis is driven by iron-dependent lipid peroxidation. Although traditional Chinese medicine （TCM） exhibits regulatory effects on cuproptosis and ferroptosis， its clinical application is hindered by poor solubility and low bioavailability. Through physical nanonization or carrier-based delivery technologies adopted by nano-TCM， the targeting specificity， stability， and bioavailability of drugs are significantly improved. By integrating sustained-release and controlled-release properties， metal ion homeostasis and redox balance in the tumor microenvironment （TME） can be precisely modulated. Research demonstrates that nano-TCM， such as celastrol-copper nanocomplexes （Cel-Cu NPs）， induces cuproptosis by augmenting intracellular copper accumulation and suppressing glutathione （GSH） levels. Nano-systems encapsulating camptothecin or artemisinin trigger ferroptosis via Fenton reaction and GSH depletion. Synergistic strategies of nano-materials， including ferrum-based metal-organic frameworks （Fe-MOFs） combined with piperlongumine， further amplify antitumor efficacy. Despite advancements in targeting cuproptosis and ferroptosis， challenges persist in nano-TCM development， including complex fabrication processes， suboptimal dosage optimization， and insufficient integration with the holistic principles of TCM. Future research should focus on exploring the interaction between cuproptosis and ferroptosis， developing multi-targeted nanodelivery systems， and fostering deeper integration of TCM theory with nanomedicine to advance novel therapeutic strategies for oncology.

Cuproptosis and ferroptosis， two recently identified metal ion-dependent forms of cell death， are triggered by homeostasis dysregulation of intracellular copper and iron， as well as oxidative stress. They demonstrate considerable potential in anti-tumor therapy. Cuproptosis arises from mitochondrial dysfunction and proteotoxic stress caused by copper overload， while ferroptosis is driven by iron-dependent lipid peroxidation. Although traditional Chinese medicine （TCM） exhibits regulatory effects on cuproptosis and ferroptosis， its clinical application is hindered by poor solubility and low bioavailability. Through physical nanonization or carrier-based delivery technologies adopted by nano-TCM， the targeting specificity， stability， and bioavailability of drugs are significantly improved. By integrating sustained-release and controlled-release properties， metal ion homeostasis and redox balance in the tumor microenvironment （TME） can be precisely modulated. Research demonstrates that nano-TCM， such as celastrol-copper nanocomplexes （Cel-Cu NPs）， induces cuproptosis by augmenting intracellular copper accumulation and suppressing glutathione （GSH） levels. Nano-systems encapsulating camptothecin or artemisinin trigger ferroptosis via Fenton reaction and GSH depletion. Synergistic strategies of nano-materials， including ferrum-based metal-organic frameworks （Fe-MOFs） combined with piperlongumine， further amplify antitumor efficacy. Despite advancements in targeting cuproptosis and ferroptosis， challenges persist in nano-TCM development， including complex fabrication processes， suboptimal dosage optimization， and insufficient integration with the holistic principles of TCM. Future research should focus on exploring the interaction between cuproptosis and ferroptosis， developing multi-targeted nanodelivery systems， and fostering deeper integration of TCM theory with nanomedicine to advance novel therapeutic strategies for oncology.

Objective:To compare the clinical outcomes of reconstruction of oral and maxillofacial soft tissue defects using superficial circumflex iliac artery perforator flap （SCIA PF） and radial forearm free flap （RFF）. Methods:A retrospective analysis was conducted on 90 patients with head, neck, and maxillofacial tumors who were treated in our department from June 2019 to January 2024. Patients were divided into two groups based on the surgical method used: the SCIA group（n=45）, who underwent reconstruction with SCIA PF, and the RFF group（n=45）, who received RFF reconstruction. Six months postoperatively, clinical efficacy was evaluated by comparing flap swelling, flap survival rate, and patient satisfaction. Oral function was assessed using standardized scoring systems before surgery, at 1 week, 3 months, and 6 months post-surgery. Hemorheological parameters, including high-shear viscosity（shear rate 200/s）, low-shear viscosity（shear rate 30/s）, plasma viscosity, erythrocyte aggregation index, and erythrocyte sedimentation rate（ESR）, were also measured at each time point. Results:Compared with the RFF group, the SCIA group showed significantly larger flap size, longer flap harvesting and reconstruction times, earlier nasogastric tube removal and oral intake initiation, higher scores in all aspects of oral function, reduced flap edema and faster resolution, higher flap survival rates, and greater overall satisfaction （all P<0.05）. During the follow-up period （preoperative, 1 week, 3 months, and 6 months post-surgery）, hemorheological indices including high-and low-shear viscosity, plasma viscosity, erythrocyte aggregation index, and ESR progressively decreased in the SCIA group （P<0.05）. In the RFF group, these parameters improved significantly by 6 months postoperatively compared with preoperatively and 1-week postoperatively, with a notable decrease in erythrocyte aggregation index at 6 months （P<0.05）. Conclusion:Compared with RFF, SCIA PF provides larger flaps, better functional recovery, higher patient satisfaction, improved flap survival, fewer complications, and more favorable hemorheological profiles following reconstructive surgery for oral and maxillofacial defects.
Humans ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Free Tissue Flaps ; Iliac Artery/transplantation* ; Forearm/surgery* ; Male ; Female ; Soft Tissue Injuries/surgery* ; Head and Neck Neoplasms/surgery* ; Middle Aged ; Treatment Outcome ; Adult

Exercise fatigue is a complex physiological and psychological phenomenon that includes peripheral fatigue in the muscles and central fatigue in the brain. Peripheral fatigue refers to the loss of force caused at the distal end of the neuromuscular junction, whereas central fatigue involves decreased motor output from the primary motor cortex, which is associated with modulations at anatomical sites proximal to nerves that innervate skeletal muscle. The central regulatory failure reflects a progressive decline in the central nervous system’s capacity to recruit motor units during sustained physical activity. Emerging evidence highlights the critical involvement of central neurochemical regulation in fatigue development, particularly through neurotransmitter-mediated modulation. Alterations in neurotransmitter release and receptor activity could influence excitatory and inhibitory signal pathways, thus modulating the perception of fatigue and exercise performance. Increased serotonin (5-HT) could increase perception of effort and lethargy, reduce motor drive to continue exercising, and contribute to exercise fatigue. Decreased dopamine (DA) and noradrenaline (NE) neurotransmission can negatively impact arousal, mood, motivation, and reward mechanisms and impair exercise performance. Furthermore, the serotonergic and dopaminergic systems interact with each other; a low 5-HT/DA ratio enhances motor motivation and improves performance, and a high 5-HT/DA ratio heightens fatigue perception and leads to decreased performance. The expression and activity of neurotransmitter receptors would be changed during prolonged exercise to fatigue, affecting the transmission of nerve signals. Prolonged high-intensity exercise causes excess 5-HT to overflow from the synaptic cleft to the axonal initial segment and activates the 5-HT1A receptor, thereby inhibiting the action potential of motor neurons and affecting the recruitment of motor units. During exercise to fatigue, the DA secretion is decreased, which blocks the binding of DA to D1 receptor in the caudate putamen and inhibits the activation of the direct pathway of the basal ganglia to suppress movement, meanwhile the binding of DA to D2 receptor is restrained in the caudate putamen, which activates the indirect pathway of the basal ganglia to influence motivation. Furthermore, other neurotransmitters and their receptors, such as adenosine (ADO), glutamic acid (Glu), and γ‑aminobutyric acid (GABA) also play important roles in regulating neurotransmitter balance and fatigue. The occurrence of central fatigue is not the result of the action of a single neurotransmitter system, but a comprehensive manifestation of the interaction between multiple neurotransmitters. This review explores the important role of neurotransmitters and their receptors in central motor fatigue, reveals the dynamic changes of different neurotransmitters such as 5-HT, DA, NE, and ADO during exercise, and summarizes the mechanisms by which these neurotransmitters and their receptors regulate fatigue perception and exercise performance through complex interactions. Besides, this study presents pharmacological evidence that drugs such as agonists, antagonists, and reuptake inhibitors could affect exercise performance by regulating the metabolic changes of neurotransmitters. Recently, emerging interventions such as dietary bioactive components intake and transcranial electrical stimulation may provide new ideas and strategies for the prevention and alleviation of exercise fatigue by regulating neurotransmitter levels and receptor activity. Overall, this work offers new theoretical insights into the understanding of exercise central fatigue, and future research should further investigate the relationship between neurotransmitters and their receptors and exercise fatigue.

ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. MethodsFrom July 19 to December 31， 2024， a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide， including their awareness and practice based on 18 questions regarding testing and referral， diagnosis and treatment， and follow-up. ResultsAmong all respondents， only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B， with an overall awareness rate of 22.0%. Only 20% ‍—‍ ‍40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy， while 80% ‍—‍ ‍100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year， 3 years， and 5 years were 67.5% 57.5% and 47.5%，respectively， showing a trend of gradual reduction， which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians， insufficient awareness of the disease among patients， and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection， diagnosis， treatment， and management” for patients with chronic hepatitis B in healthcare institutions， in order to promote the implementation of the guidelines.