ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

OBJECTIVE: To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

Objective To investigate the effect of rats'injuries and its mechanism caused by specific dose of radiation combined with decompression exposure.Methods 81 male SD rats were randomly divided into control group(n=9),radiation group(n=18),radiation+low-load decompression group(n=18),radiation+medium-load decompression group(n=18),and radiation+high-load decompression group(n=18).In addition to control group,the rats were irradiated with 60Co γ rays at 4 Gy and then underwent rapid escape experiments.The high-pressure exposure schemes were to stay underwater 57 m for 30 min,45 min or 60 min and reduce to normal pressure within(30±5)s,respectively.The high-pressure exposure was not carried out in radiation group.The behavior and death of rats in each group were observed 0.5 h after leaving the cabin.Blood(abdominal aorta)and lung tissues were collected at 3 h and 72 h,respectively.The changes of lung wet-dry weight ratio(W/D),lung pathology and serum levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),intercellular adhesion molecule-1(ICAM-1)and thromboxane B2(TXB2)were analyzed.Results Compared with control group and radiation group,radiation+low-load decompression group showed no significant difference in the injury and death rate of rats(P＞0.05),while radiation+medium-load decompression group and radiation+high-load decompression group showed significantly increase of the injury and death rate of rats(P＜0.05).Compared with control group,other groups showed no significant change in pulmonary W/D at 3 h(P＞0.05),and increased at 72 h(P＜0.05).HE staining showed that compared with control group,radiation group showed mild lung interstitial edema,while radiation+low-load decompression group showed obvious pulmonary tissue edema and a small number of red blood cells exudated in the alveolar cavity.The edema,congestion and inflammatory cell infiltration of lung tissue were more serious in radiation+medium-load decompression group and radiation+high-load decompression group.Compared with control group and radiation group,all radiation+decompression groups showed an increase in serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2(P＜0.05),and a decrease in SOD activity(P＜0.05).Compared with radiation+low-load decompression group,radiation+medium-load decompression group and radiation+high-load decompression group showed increase in serum levels of IL-1β,IL-6,MDA,ICAM-1 and TXB2(P＜0.05),and decrease in activity of SOD(P＜0.05).Except for control group,serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2 were decreased at 72 h compared with 3 h(P＜0.05),and SOD activity was increased at 72 h in all groups(P＜0.05).Conclusions High-load decompression can increase the injury and death rate of rats exposed to radiation and high pressure.The potential mechanism of the combined injury effect of radiation and decompression was related to inflammation,immune stress,oxidative damage,vasomotor activity and coagulation mechanism.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.