Objective To investigate the effects and mechanisms of peimine(PME)on chronic obstructive pulmonary disease(COPD)in mice.Methods The mice were randomly divided into 4 groups(20 mice in each group),control group,PME group,chronic obstructive pulmonary disease group and treatment group.Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke.The effects of PME on COPD model mice was analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on COPD model mice were analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on inflammatory factor tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting.The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium(DHE)staining and Western blotting.The effects of PME on nuclear factor kappa-B(NF-κB)pathway and nuclear factor erythroid 2-related factor 2(Nrf2)pathway were analyzed by protein immunoblotting.Results Compared with the COPD group,PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice,and the wet/dry weight ratio of lung tissue was significantly reduced.Compared with the control group,the levels of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced.In addition,compared with the control group,the protein expression of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced.Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2)protein in COPD group was significantly lower than that in control group,while PME treatment could improve the level of superoxide dismutase protein.The analysis of MDA content in lung tissue showed that compared with the COPD group,the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment.Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα)and the transfer of NF-κB p65 to the cell nucleus,and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1)in the lung tissue of mice treated with PME significantly increased.Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.
Humans ; Multiple Sclerosis/pathology* ; Remyelination/physiology* ; Myelin Sheath/pathology* ; Inflammation/drug therapy* ; Homeostasis

The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Objective     To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods     Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results     From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second-line treatment. Conclusion     Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.

The study aimed to examine the applicability of carbon nanoparticles as a tracer for lymph node mapping and the related factors of lymph node and No.8p subgroup metastasis in patients with gastric cancer. Clinical data of 50 patients with gastric cancer, who had not received treatment preoperatively and underwent gastrectomy in Department of Gastrointestinal Surgery, Wuhan Union Hospital, between October 2014 and August 2015, were retrospectively analyzed. These patients were found to have no distant metastasis preoperatively. Thirty-five out of 50 patients were subjected to lymphatic mapping technique using carbon nanoparticles as the tracer, and the rest 15 cases did not experience the lymphatic mapping and served as controls. The sensitivity, specificity, false positive rate and false negative rate were calculated according to the number of lymph nodes, and the staining and metastasis condition of lymph nodes. The diagnostic value of carbon nanoparticles on metastatic lymph nodes was evaluated. The relationship between the metastasis of lymph nodes or subgroup No.8p lymph nodes and clinicopathologic features was analyzed by χ-test or Fisher's exact test. All patients underwent D2 surgery (lymph node dissection including all the group 1 and group 2 nodes) plus the dissection of the subgroup No.8p lymph nodes. It was found that the average number of harvested lymph nodes in lymphatic mapping technique group (45.7±14.5) was greater than that in control group (39.2±11.7), but the difference was not significantly different (P=0.138>0.05). The success rate, the accuracy, sensitivity, specificity and false negative rate was 97%, 57%, 28%, 62% and 72% respectively. The metastasis of lymph nodes was correlated to the depth of cancer invasion (T stage) (P=0.004<0.05), and the metastasis of No.8p lymph nodes was correlated to the extent of lymph node involvement (N stage) (P=0.007<0.05). Six cases had lymph node metastasis in subgroup No.8p, and their TNM stages and clinical stages were as follows: T1N2M0 IIA, T3N3M0 IIIB, T4aN3M0 IIIC, T4aN3M0 IIIC, T4aN3M0 IIIC, and T4bN3M0 IIIC. In conclusion, our study indicated that carbon nanoparticles failed to show good selectivity for metastatic lymph nodes; the result of lymphatic mapping does not achieve a satisfactory performance; the incidence of lymph node metastasis may increase, accompanying with the increase of the depth of cancer invasion; No.8p lymph node metastasis tends to occur for gastric carcinoma patients with the extent of lymph node metastasis over N2 stage.
Adolescent ; Adult ; Aged ; Carbon ; Carcinoma ; diagnostic imaging ; pathology ; surgery ; Female ; Humans ; Lymph Nodes ; diagnostic imaging ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nanoparticles ; administration & dosage ; adverse effects ; chemistry ; Sensitivity and Specificity ; Stomach Neoplasms ; diagnostic imaging ; pathology ; surgery

OBJECTIVETo explore the effects of percutaneous transhepatic radiofrequency ablation (PRFA) combined with tumor edge of percutaneous absolute ethanol injection (PEI) on liver cancer adjacent to major blood vessels.

METHODSSeventy five patients with liver cancer adjacent to major blood vessels were randomly divided into two groups: PRFA+PEI therapy group (38 cases) and PRFA control group (37 cases). Tumor necrosis rate, AFP levels, local recurrence rate, median for survival time and cum survival were used as the evaluation index to evaluate the efficacies of the two methods.

RESULTSTumor necrosis rates of the therapy group and the control group were 84.2% and 54.1% (P < 0.01), respectively; AFP levels of therapy group and control group at 1, 3, 6 and 12 months after treatment were (105.0 ± 35.5) μg/L, (28.4 ± 4.3) μg/L, (58.6 ± 6.7) μg/L, (89.5 ± 12.5) μg/L and (137.2 ± 34.6) μg/L, (84.2 ± 18.4) μg/L, (106.6 ± 20.3) μg/L, (173.7 ± 32.0) μg/L, respectively. The rates of therapy group was significantly lower than of control group. Local recurrence rates of the therapy group and control group were 2.6%, 7.9%, 13.2% and 31.6% vs 10.8%, 21.6% , 40.5% and 62.1% (P < 0.05) at 3, 6, 12 and 24 months after treatment, respectively. Median for survival time of the therapy group and control group were 28.0 ± 2.8 months and 19.0 ± 3.6 months, respectively. Cum survival of the therapy group and control group were 84.2%, 78.9%, 60.5% and 31.6% vs 78.4%, 67.6%, 37.8% and 8.1% (P < 0.05) at 6, 12, 24 and 36 months after treatment, respectively.

CONCLUSIONPEI as a supplementary treatment of PRFA can effectively improve the treatment of liver cancer adjacent to major blood vessels and significantly reduce the local recurrence rate and improve long-term survival rates.

Adult ; Aged ; Bile Duct Neoplasms ; Carcinoma, Hepatocellular ; pathology ; therapy ; Catheter Ablation ; Combined Modality Therapy ; Ethanol ; administration & dosage ; Female ; Humans ; Liver Neoplasms ; pathology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome