ObjectiveThe paper aims to investigate the mechanism by which Xiaozheng Zhitong paste （XZP） alleviates bone cancer pain （BCP） through regulating the PTEN-induced putative kinase 1 （PINK1）/Parkin-mediated mitophagy-NOD-like receptor protein 3 （NLRP3） inflammasome pathway to suppress microglial pyroptosis. MethodsLipopolysaccharide （LPS） and LPS-adenosine triphosphate （ATP） were used to establish an inflammation and pyroptosis model in microglial cells. The cells were randomly divided into the following groups： control group， LPS group， LPS+low-dose XZP group， LPS+high-dose XZP group， LPS-ATP group， LPS-ATP+low-dose XZP group， LPS-ATP+high-dose XZP group， LPS-ATP+XZP group， and LPS-ATP+XZP+CsA group. Techniques including terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining， enzyme-linked immunosorbent assay （ELISA）， Western blot， and confocal fluorescence staining were employed to assess the effects of XZP on microglial apoptosis， inflammatory cytokine release， inflammasome activation， pyroptosis， and mitophagy. ResultsIn vitro experiments showed that compared with the blank group， the LPS group exhibited significantly increased levels of microglial apoptosis and pro-inflammatory factors interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α）（P<0.01）， along with significantly upregulated protein expression of inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX-2）， and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） （P<0.01）. Compared with the LPS group， the high-dose LPS-XZP group significantly reduced the level of apoptosis （P<0.01） and the content of the aforementioned pro-inflammatory factors （P<0.01）. Both the low- and high-dose LPS-XZP groups dose-dependently downregulated the protein expression of iNOS， COX-2， and p-NF-κB p65 （P<0.05， P<0.01）. Compared with the blank group， the LPS-ATP group showed significantly upregulated expression of pyroptosis-related proteins， including Caspase-1/pro-Caspase-1， N-terminal fragment of gasdermin D （GSDMD-N）/full-length gasdermin D （GSDMD-F）， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β precursor （pro-IL-1β）， and mature IL-1β （P<0.01）. The levels of pyroptotic factors IL-1β and IL-18 were significantly elevated （P<0.01）， and membrane pore formation and intracellular reactive oxygen species （ROS） levels were significantly increased （P<0.01）. Compared with the LPS-ATP group， both the low- and high-dose LPS-ATP+XZP groups dose-dependently downregulated the expression of the aforementioned pyroptosis-related proteins （P<0.05， P<0.01）. The low-dose LPS-ATP+XZP group reduced IL-1β levels （P<0.01）， while the high-dose group reduced both IL-1β and IL-18 levels （P<0.01） Both the low- and high-dose LPS-ATP+XZP groups dose-dependently reduced membrane pore formation and intracellular ROS production （P<0.01）. Compared with the blank group， the LPS-ATP group showed significantly reduced expression of mitophagy-related proteins PINK1 and Parkin， and a decreased ratio of microtubule-associated protein 1 light chain 3Ⅱ（LC3Ⅱ） to LC3Ⅰ（P<0.01）， while p62 expression was significantly increased （P<0.01）. Mitochondrial ROS levels were significantly enhanced （P<0.01）. Compared with the LPS-ATP group， both the low- and high-dose LPS-ATP+XZP groups dose-dependently reversed the expression of these proteins （P<0.05， P<0.01） and reduced mitochondrial ROS levels （P<0.01）. After treatment with the mitophagy inhibitor cyclosporin A （CsA）， the beneficial effects of XZP on mitochondrial function and its inhibitory effects on pyroptosis-related protein expression were significantly reversed （P<0.05， P<0.01）. ConclusionXZP reduces ROS levels by activating PINK1/Parkin-mediated mitophagy， thereby inhibiting NLRP3 inflammasome activation and microglial pyroptosis， which provides new molecular evidence for the mechanism by which XZP alleviates BCP.

ObjectiveTo investigate the effects and underlying mechanisms of Xiaozheng Zhitong Paste （XZP） on bone cancer pain （BCP）. MethodsThirty female BALB/c mice were randomly divided into five groups： a Sham group， a BCP group， a BCP+low-dose XZP group， a BCP+high-dose XZP group， and a BCP+high-dose XZP + protease-activated receptor 2 （PAR2） agonist GB-110 group. BCP mice model was constructed by injecting Lewis lung carcinoma cells into the femoral cavity of the right leg， which was followed by being treated with XZP for 21 d. After 21 d， the mice were sacrificed. Nissl staining was used to evaluate the survival of spinal cord neurons. Immunofluorescence staining was conducted to localize ionized calcium-binding adapter molecule 1 （Iba1） and neuronal nuclear antigen （NeuN） in spinal cord tissue， thereby assessing microglial activation and neuronal survival. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， transforming growth factor-β （TGF-β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in spinal cord tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels associated with M1/M2 polarization of microglia. Western blot analysis was performed to examine the expression of proteins related to microglial polarization as well as those involved in the PAR2/nuclear factor kappa B （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway in the spinal cord. ResultsCompared with the Sham group， the spinal cord neurons were damaged， the number of Nissl-positive spinal cord neurons in the spinal cord tissue was significantly reduced （P<0.01）， and the rate of NeuN-positive cells was significantly decreased （P<0.01）. The spinal cord microglia were activated， the inflammatory level of the spinal cord tissue was enhanced， and Iba1 staining was significantly enhanced （P<0.01）. The levels of IL-1β， TNF-α， IL-6， TGF-β， IL-4 and IL-10 were significantly increased （P<0.01）. The mRNA expressions of IL-1β， TNF-α and inducible nitric oxide synthase （iNOS） were significantly increased （P<0.01）， and the expression of PAR2， NLRP3， ASC and NF-κB p65 proteins in the spinal cord tissue of the BCP mice was significantly enhanced （P<0.01）. Compared with the BCP group， high-dose XZP treatment significantly increased the number of Nissl-positive spinal cord neurons in the BCP mice （P<0.01）， significantly enhanced the rate of NeuN-positive cells in the spinal cord tissue， and significantly weakened Iba1 staining （P<0.01）. In addition， the levels of IL-1β， TNF-α， and IL-6 were significantly decreased， while the levels of TGF-β， IL-4， and IL-10 were significantly increased （P<0.05， P<0.01）. The mRNA expression levels of IL-1β， TNF-α， and iNOS were decreased， whereas those of cluster of differentiation 206 （CD206）， arginase-1 （Arg-1）， and YM1/2 were significantly increased （P<0.05， P<0.01）. Low-dose and high-dose XZP treatment significantly decreased the expression of PAR2， NLRP3， ASC， and NF-κB p65 proteins in the spinal cord tissue （P<0.05， P<0.01）. These effects could all be significantly eliminated by the PAR2 agonist GB-110. ConclusionXZP can mitigate BCP in mice， which may be achieved through blocking the activated PAR2/NF-κB/NLRP3 pathway.

Cancer pain is one of the most common complications in patients with malignant tumors， severely affecting their quality of life. Its pathogenesis involves complex interactions among the tumor microenvironment， peripheral sensitization， and central sensitization. The tumor microenvironment initiates peripheral pain sensitization by secreting algogenic mediators， activating ion channels and related receptor signaling pathways， driving abnormal osteoclast activation， and mediating neuro-immune crosstalk. Persistent nociceptive input further triggers increased excitability of central neurons， activation of glial cells， and neuroinflammatory cascade reactions， ultimately leading to central pain sensitization. Although traditional opioid drugs can alleviate pain to some extent， they still have many limitations， such as incomplete analgesia， drug tolerance， and adverse reactions. In recent years， traditional Chinese medicine （TCM） compounds have made continuous progress in the treatment of cancer pain. Studies have shown that they can not only effectively relieve cancer pain and reduce the dosage of opioids but also significantly improve patients' quality of life. TCM treatment of cancer pain follows the principle of syndrome differentiation and treatment. Based on this， targeted therapeutic principles have been proposed， including promoting blood circulation， removing stasis， regulating Qi， and unblocking collaterals； tonifying the kidney， replenishing essence， warming Yang， and dispersing cold， activating blood， resolving phlegm， detoxifying， and dispersing nodules， as well as strengthening the body， replenishing deficiency， and harmonizing Qi and blood. Modern research indicates that TCM compounds can exert synergistic effects through multiple pathways， inhibiting inflammatory responses， regulating nerve conduction， intervening in bone metabolism and related gene expression， thereby producing anti-inflammatory and bone-protective effects to achieve the goal of alleviating cancer pain. This article systematically elaborates on the pathogenesis of cancer pain， the clinical application of TCM in treating cancer pain， and its related mechanisms of action， aiming to provide a theoretical basis and new strategies for the integration of TCM into comprehensive cancer pain management.

Pain， as one of the most common symptoms in cancer patients， seriously affects the survival quality of patients. The three-step pain relief program currently used in clinical practice cannot completely relieve pain in cancer patients and is accompanied by many problems. From the perspective of Jueyin syndrome in traditional Chinese medicine （TCM）， this paper believed that the core pathogenesis of cancer pain was declined healthy Qi and cold and heat in complexity， and used Wumeiwan as the main formula with modification according to syndrome for clearing the upper， warming the lower part of the body， and harmonizing the cold and heat. It can regulate the pathological environment of deficiency， cold， stasis， toxicity， and heat， and restore the physiological function of Yang transforming Qi while Yin constituting form， so as to prevent， relieve， and even eliminate cancer pain， having achieved good clinical efficacy. It can not only help cancer patients relieve pain， but also control tumor and eliminate tumor， achieving a dual benefit of pain relief and tumor suppression. It gives full play to the characteristics and advantages of syndrome differentiation and treatment in TCM， and expands the scope of ZHANG Zhongjing's treatment for Jueyin syndrome， which provides ideas for the clinical diagnosis and treatment of cancer pain from the perspective of deficiency-excess in complexity and cold and heat in complexity.

Objective:To comprehensively analyze the medical resources and services supply in the cancer field of China.Methods:Data of 2018 were sampled from 41 tertiary public cancer hospitals in China, and the factor analysis method was used to extract common factors in resources or services, scoring respectively. Pearson correlation analysis was used in the collinearity test of the variables of both groups of common factors, while the second-order clustering method was used to analyze characteristic differences between the hospitals, and category difference was compared with t test. Results:Resource evaluation covered the two dimensions of basic resources(medical service and basic assurance resources)and high-end resources(high-end talents and academic resources). Service evaluation covered the two dimensions of medical service assurance(clinical services and basic assurance)and disciplinary sphere of influence(discipline construction and clinical efficiency). The factor of basic manpower and beds was significantly correlated with that of medical service and basic assurance( r=0.811, P<0.001), while the factor of high-end talents and academic resources was significantly correlated with that disciplinary construction and resource efficiency( r=0.906, P<0.001). The second-order cluster analysis found the 41 cancer hospitals as two categories, with the first category of five in Guangdong, Shanghai, Beijing and Tianjin, and the second category of the rest 36 hospitals. Significant differences were found between the two categories in terms of resource scoring, service scoring, high-end resources and disciplinary sphere of influence( P<0.001). Meanwhile, the GDP per capita of the cities in which these hospitals are located also had significant differences( P<0.001). Conclusions:Development of public tertiary cancer hospitals in China was imbalanced, as their differences were mainly found in levels of disciplinary development and efficiency of clinical services, which were closely related to the high-end talents and academic resources of the hospital in question.Furthermore, high quality medical care was mostly located in regions of higher development. The authors recommend to take a balanced consideration of the differences and distribution of cancer care services in China, in terms of performance classification of public hospitals and establishment of regional cancer centers of the country.

Objective To explore the clinical efficiency and safety of radiofrequency ablation combined with Tegafur,Gimeracil and Oteracil Porassium Capsules( S-1 capsules) for hepatocellular carcinoma.Methods Sixty HCC patients included in this study were underwent initial radiofrequency ablation and then they were di-vided into RFA+S-1 group and RFA control group according to the metronomic chemotherapy either with S-1 or not.The local tumor control and disease free survival outcome between the two groups were compared.Results Follow-up observation showed that the total control rate after 9 months′treatment was 93.3%in RFA+S-1 group vs.73.4%in RFA control group(P=0.038).During the 18 months of follow up,the median time for dis-ease free survival was 16.25 months in RFA+S-1 group vs.12.25 months in RFA control group( P<0.001) . One-year progression free survival rate in RFA group was 53.3%,which was significantly lower than the RFA+S-1 group(83.3%)(P=0.012).The major complication rate was 13.3%.No procedu rerelated death or severe complications occurred.Conclusion Metronomic chemotherapy with S-1 following initial radiofrequency ablation delays tumor progression and prolongs overall survival of patients with HCC tumors.

Objective To investigate the clinical effect and to summarize the experience of percutaneous radiofrequency ablation (RFA) of spleen together with splenic artery balloon block in treating hypersplenism due to cirrhosis and portal hypertension. Methods Under the situation of splenic artery occlusion with balloon, RFA of the spleen was performed in 15 patients with hypersplenism caused by cirrhosis and portal hypertension. The mean duration of RFA was (46.4±5.4) min. Routine blood tests were conducted at 3 days, one week, one, 3 and 6 months after the treatment, and abdominal CT angiography was performed one month after RFA. The results were analyzed. Results One patient developed massive bloody pleural effusion at left thorax three days after RFA, which was improved after hemostasis and thoracic drainage. No severe complications occurred in other patients. Abdominal CT angiography performed one month after RFA showed that the ablated extent by RFA was accounted for about 34.3%-71.8% proportion of the spleen, with a mean of (56.20 ±13.09)%. Preoperative blood tests indicated that the count of white blood cells, red blood corpuscles and blood platelets was (3.88±1.75)×109/L, (4.06±0.37) × 1012/L and (48.14± 11.33)×109/L, respectively. One month after RFA the count of white blood cells and blood platelets increased to (5.62±1.61) ×109/L and (132.29±33.20) ×109/L respectively. When compared with the preoperative data, the differences in the count of white blood cells and blood platelets were statistically significant (P<0.05). Conclusion For the treatment of hypersplenism due to cirrhosis and portal hypertension, percutaneous radiofrequency ablation of spleen together with splenic artery balloon block is quite safe and this technique has satisfactory short-term effect.

Objective To investigate the changes in the serum level of vascular endothelial growth factor (VEGF) in experimental Wistar rats with hepatic alveolar echinococcosis (HAE) after hepatic arterial infusion (HAI) of bevacizumab treatment, and to discuss the efficacy of HAI of bevacizumab for hepatic alveolar echinococcosis. Methods Forty Wistar rats with successfully established HAE were randomly and equally divided into two groups with 20 rats in each group: the control group and the study group. Hepatic arterial infusion of saline was performed in the rats of the control group , while hepatic arterial infusion of bevacizumab was carried out in the rats of the study group. Before and 7, 14, 21 and 28 days after the treatment peripheral blood samples were collected from the tail vein, and the serum levels of VEGF, apartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined by the quantitative sandwich enzyme-linked immunosorbent assay (ELISA). All the rats were sacrificed 28 days after the treatment. HAE samples were examined to evaluate the effect of bevacizumab on HAE lesions. Results Seven days after hepatic arterial infusion of bevacizumab, serum VEGF expression level in the study group became gradually decreased, and the difference was statistically significant when compared with the preoperative level or with that in the control group (P = 0.019). Fourteen days after the treatment, the serum VEGF expression level kept going down to its lowest point, and the difference in serum VEGF expression level was statistically significant when compared with the preoperative level (P < 0.01). Twenty-one days after the treatment, serum VEGF expression level started to rise and it returned to normal level in 28 days after the treatment. In the control group no significant changes in serum VEGF expression levels was observed after hepatic arterial injection of saline (P > 0.05). Conclusion In treating hepatic alveolar echinococcosis, hepatic arterial infusion of bevacizumab has certain inhibitory effect on angiogenesis. This therapy is safe and effective.