The efficiency of neoadjuvant chemotherapy in colon cancer with mismatch repair deficiency.

Colon cancers with mismatch repair deficiency (dMMR) have specific clinicopathologic characteristics compared with mismatch repair proficiency (pMMR); however, the effect of MMR status on the efficiency of neoadjuvant chemotherapy (NCT) remains unclear. In our study, 439 dMMR and 26 pMMR colon cancer patients with or without NCT from 2010 to 2017 were retrospectively collected. Clinicopathological features, treatment response, and survival were compared between different groups. In the dMMR group, patients with NCT were likely to have higher CEA (abnormal CEA: 51.6% vs. 17.4%, p < 0.001), more multiorgan resection (38.7% vs. 16.8%, p = 0.006), and larger postoperative tumor diameter (7.26 vs. 6.21, p = 0.033) than those without NCT, but nearly half of cT4b patients who had NCT (42.9%, 9/21) avoid multiorgan resection. pT4 stage (HR, 14.97; 95% CI, 1.88-118.92; p = 0.010), number of positive lymph nodes (HR, 1.17; 95% CI, 1.09-1.26; p < 0.001), and tumor deposit (HR, 6.73; 95% CI, 2.08-21.74; p = 0.001) were independent prognosis factors of disease-free survival (DFS). For the advanced tumor subset, there is no significant difference between patients with or without NCT for OS (p = 0.13) and DFS (p = 0.11), although the survival rate of NCT was higher than non-NCT patients. Moreover, tumor regression grade was similar between dMMR and pMMR patients who had NCT. This study showed that NCT was more likely to be employed in dMMR patients with advanced tumors and may reduce the rate of multiorgan resection for cT4b dMMR patients. More large-scaled researches are needed to further explore if MMR status could predict the efficacy of neoadjuvant chemotherapy in patients with colon cancer.

Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid / 药物分析学报

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological com-ponents of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the meta-bolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the in-flammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed

Reflections on the era of valvular intervention—The perspective of surgeons / 中国胸心血管外科临床杂志

@#In recent years, the number of interventions for valvular heart disease has been increasing day by day, and it has become a hot topic in the field of cardiovascular surgery. Given the aging global population and trends in the prevalence of valvular disease and the broadening of indications for transcatheter aortic valve replacement (TAVR), a breakthrough of 130 000 TAVR procedures is expected by 2026. In the new technology development period, the development potential and technical advantages of heart valve interventional therapy should be faced squarely. This paper focuses on key issues such as comparison of outcomes after TAVR versus surgical aortic valve replacement (SAVR), prosthetic valve endocarditis after TAVR, and broadening of indications for TAVR, as well as recommendations on how surgeons face the era of TAVR. We hope that this article will help and attract the attention of cardiac surgeons.

The efficacy and safety of surgical treatment after neoadjuvant chemotherapy for cT4N+ colon cancer / 中华肿瘤杂志

Objective@#To evaluate the safety and efficacy of surgical treatment after neoadjuvant chemotherapy (NCT) for patients with cT4N+ colon cancer, and to explore whether the indication of NCT for colon cancer can be extended from cT4b to cT4N+ .@*Methods@#The clinical data of 40 patients with cT4N+ colon cancer who underwent neoadjuvant chemotherapy followed by surgical treatment was retrospectively analyzed. The safety of neoadjuvant chemotherapy, surgical complications, R0 resection rate, tumor regression grade and prognosis were evaluated.@*Results@#Of the 40 patients, 23 were male and 17 were female; the median age was 57 years old. All patients were well tolerated with chemotherapy, and only one case (1/40, 2.5%) had grade 3 chemotherapy-related adverse event. They all underwent surgery after chemotherapy, and 95.0% (38/40) achieved microscopically clear resection (R0). Of the 11 patients with cT4b, 54.5% (6/11) had undergone multivisceral resection (MVR). Postoperative pathological results showed that 12 patients had moderate to severe tumor regression, including one(1/40, 2.5%) achieved pathologic complete response (pCR). 29(72.5%) and 22 (55.0%) patients achieved down-staging of tumor T stage and N stage, respectively. The occurrence of surgical complications was 22.5% (9/40), including one case of anastomotic leakage (1/40, 2.5%). The 3-year disease-free survival and overall survival of the whole group were 75.0% and 80.0%, respectively.@*Conclusion@#Surgery after neoadjuvant chemotherapy is safe and effective for patients with cT4N+ colon cancer, therefore indications for neoadjuvant chemotherapy for advanced colon cancer can be extended to cT4N+ stage.

The association of metastasis-related indexes of lymph nodes and the prognosis of stage N2b colorectal cancer patients / 中华肿瘤杂志

Objective@#To evaluate the prognostic value of lymph node metastasis-related indexes in patients with stage N2b colorectal cancer.@*Methods@#Clinicopathologic data of 245 patients with stage N2b colorectal cancer who initially underwent radical operation in Cancer Hospital, Chinese Academy of Medical Sciences between January 2007 and December 2012 were retrospectively analyzed. The prognostic values of several indexes, including number of positive lymph nodes, number of negative lymph nodes, lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) were analyzed.@*Results@#The 5-year overall survival rate of 245 patients with colorectal cancer was 54.0%, and the 5-year recurrence-free survival rate was 48.5%.Univariate analysis showed that perineural or blood vessel invasion, T stage, postoperative adjuvant therapy, number of positive lymph nodes, number of negative lymph nodes, LNR, and LODDS were significantly associated with the 5-year overall survival of colorectal cancer patients (P<0.05). Multivariate cox regression analysis showed that, number of positive lymph nodes, number of negative lymph nodes, LNR, LODDS were all independent prognostic factors for stage N2b colorectal cancer patients (P<0.05). The areas under the receiver operating characteristic curve (ROC) curves of number of positive lymph node, number of negative lymph nodes, LNR and LODDS were 0.649, 0.667, 0.690 and 0.683, respectively, however, no statistical significance was observed between the number of negative lymph nodes (P=0.622), LNR (P=0.178) or LODDS (P=0.272) and the number of positive lymph nodes.@*Conclusion@#The number of positive lymph nodes, number of negative lymph nodes, LNR and LODDS were all independent prognostic factors for patients with stage N2b colorectal cancer.

[Exploratory study on influence of biopsy to biological behavior of Tca8113 transplanted tumor].

OBJECTIVE: We established an animal model of nude mice with Tca8113 tumor and cut some tissue for biopsy. We also determined the biological behavior and mechanisms of the tumor. METHODS: The mice were divided into two groups randomly. Mice in both groups were injected with Tca8113 cells into their tongues. The survival condition, growth of primary focus, and metastasis were observed. Hematoxylin and eosin staining and immunohistochemistry were performed on nuclear factor κB (NF-κB), matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 (SDF-1), and Ki67 to determine their distributions within the tumor. Cytokeratin staining was also performed to detect micrometastasis in the submandibular lymph nodes. RESULTS: The emerging rate of tumor was 97.92%. The weight and survival time of the experimental group were lower than that of the control group, whereas the metastasis ratio was higher. The expression of NF-κB, MMP-9, SDF-1, and MMP-9 in tumors was higher in the experimental group than that in the control group. The expression of NF-κB, MMP-9, VEGF, and SDF-1 was relevant. The microvessel density of the experimental group was higher than that in the control group. CONCLUSIONS: Biopsy can affect the biological behavior of tongue tumor and can promote growth of primary focus and metastasis.

Differential effects of estrogen and estrogen receptor antagonist, ⅡCI 182780 on the expression of Calbindin-D9k in rat pituitary prolactinoma GH3 cells / 中华内分泌外科杂志

Objective To detect the effects of 17 β-estradiol(E2)on the expression of Calbindin-D9k (CaBP-9k) in pituitary GH3 cells,and to investigate the antagonistic effect of a selective estrogen receptor antagonist,ⅡCI 182780 on CaBP-9k expression.Methods A rat pituitary prolactinoma cell line,GH3 cell was used as the in vitro model.The localization of CaBP-9k in GH3 cells was observed by immunofluorescence.GH3 cells were cultured with exogenous E2-added medium for 24 hours,and the concentrations of E2 were 10-8,10-9,10-10M,respectively.mRNA and protein expression levels of CaBP-9k in different groups were analyzed by RT-PCR and Western blot analysis.The estrogen receptor antagonist,and ⅡCI 182780 was added to GH3 cells before E2 administration (10-8M)with the concentration of 10-6M,in order to investigate the regulation of ER-mediated pathway on the expression of CaBP-9k.Immunoprecipitation was used to detect the interaction between CaBP-9k and ERα.Results E2 had significant stimulatory effect on the CaBP-9k expression of GH3 cells in a dose dependent manner,and the expression level of CaBP-9k was higher when treated with a higher concentration of E2.ⅡCI 182780 could suppress the stimulatory effect of E2 on the CaBP-9k expression of GH3 cells.The expression level of CaBP-9k was significantly reduced by coadministration of E2 with ⅡCI 182780 in GH3 cells,which meant the CaBP-9k expression was mediated through ERα pathway.The immunoprecipitation results further illustrated the fact that CaBP-9k could directly interact with ERα,and E2 could increase the interaction between CaBP-9k and ERα.Conclusion Estrogen might induce CaBP-9k expression via ERα mediated pathway and CaBP-9k could directly combine with ERα,suggesting that CaBP-9k might be involved in the biological effects mediated by ER pathway in GH3 cells.

Relationship between distribution of infected snails and transmission of acute schistosomiasis in hilly regions / 中国血吸虫病防治杂志

Objective To explore the relationship between the distribution of infected snails and transmission of acute schistosomiasis in hilly regions.Methods The data concerning the distribution of the infected snails and acute schistosomiasis in Shitai County,Anhui Province from 1999 to 2008 were collected and analyzed.Results The sehistosome infection rate of human increased as the distance between the settings with infected snails and activity sites of humans shortened.Conclusions Acute infection of schistosome of human is associated with the distance between the settings with infected snails and activity sites of them.Strengthening the measures of snail control in key regions,protecting key populations and carrying out health education for schistosomiasis control are important approaches to control the transmission of acute schistosomiasis in hilly regions.