Objective:To learn about the single nucleotide polymorphism (SNP) population structure and regional distribution characteristics of Yersinia pestis in the natural focus of plague in Qinghai-Tibet Plateau. Methods:A total of 319 representative strains of Yersinia pestis isolated from natural focus of plague in Qinghai-Tibet Plateau from 1954 to 2020 were selected, and 2 298 SNP loci included in the global Yersinia pestis phylogenetic tree were compared by whole genome sequencing technology. MEGA 6.0 software was used to construct phylogenetic trees of 319 strains of Yersinia pestis from Qinghai-Tibet Plateau, determine the SNP population structure of Yersinia pestis in the focus, and describe its regional distribution characteristics. Results:The 319 strains of Yersinia pestis isolated from Qinghai-Tibet Plateau natural plague foci were distributed in 5 clades, namely 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED. The 1.IN clade contained 209 strains (65.52%, 209/319), which was the dominant population of strains in Qinghai Province, accounting for 90.51% (143/158). The 2.ANT clade contained 83 strains (26.02%, 83/319), which was the dominant population in Tibet Autonomous Region, accounting for 67.24% (78/116). The 3.ANT, 0.PE, and 2.MED clades contained 12 (3.76%, 12/319), 9 (2.82%, 9/319) and 6 strains (1.88%, 6/319), respectively, which were scattered in Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region under the jurisdiction of Qinghai-Tibet Plateau. Conclusion:The SNP population structure of Yersinia pestis in natural focus of plague in Qinghai-Tibet Plateau is relatively rich, and the strains are distributed in 5 clades: 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED, showing the distribution characteristics of specific regions.

ObjectiveTo analyze the effects of polydatin on myeloma cell growth，apoptosis， and reactive oxygen species（ROS）/p38 mitogen-activated protein kinase（MAPK） signaling pathway. MethodHuman multiple myeloma （MM） cell line U266 cells were cultured in vitro，and the effects of polydatin at 0，20，40，80，160，200 mg·L^-1 on the growth of U266 cells were detected by cell counting kit-8（CCK-8）assay. The half-maximal inhibitory concentration（IC₅₀）was calculated. U266 cells in the logarithmic growth phase were randomly divided into a control group， low- and high-dose polydatin （80 and 160 mg·L^-1） groups， and a bortezomib （75 nmol·L^-1） group. After treatment with corresponding drugs，the cell viability of each group was determined by CCK-8 assay. The apoptosis rate of each group was measured by flow cytometry. The levels of inflammatory factors， such as tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β）， and ROS in each group were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expression levels of apoptosis-related factors， including cysteine aspartate-specific protease-9（Caspase-9），B-cell lymphoma-2-associated X protein（Bax），p38 MAPK，and phosphorylated （p）-p38 MAPK in each group were detected by Western blot. ResultCompared with the results in the control group， polydatin of different concentrations could inhibit the growth of U266 cells （P<0.05），and the effect was potentiated with the increase in the concentration，with IC₅₀ of 156.54 mg·L^-1. Compared with the control group，the groups with drug treatment showed blunted cell viability （P<0.05） and increased apoptosis rate，TNF-α，IL-1β，and ROS levels， protein expression levels of Caspase-9， Bax，and p-p38 MAPK/p38 MAPK （P<0.05）. Compared with the low-dose polydatin group， the high-dose polydatin group and the bortezomib group showed improved indicators mentioned above （P<0.05）， and there was no significant difference between the high-dose polydatin group and the bortezomib group. ConclusionPolydatin can activate the ROS/p38 MAPK signaling pathway，promote the expression of inflammatory factors，inhibit the growth of U266 cells，and promote their apoptosis.

Objective:To explore the correlation of the dose of capecitabine with the efficacy and cardiotoxicity in patient-derived tumor xenograft (PDX) model of mice with colorectal cancer.Methods:The fresh cancer tissues of 1 colorectal cancer patient were transplanted into the bilateral axillary subcutaneous of immunodeficient NOG mice to establish PDX model and passage stably. And then the morphology of tumor cells in primary generation and the second-generation tumor tissues was observed by using HE staining. The expression of tumor markers was detected by using immunohistochemistry method, and the model was evaluated. Mice were intragastrically infused with 200, 300 and 400 mg/kg capecitabine once a day, which were treated as low, middle and high dose groups respectively, 5 rats in each group; in the control group, 0.9% NaCl solution was perfused into the stomach; 14 d in total, use stop for 7 d, consecutively administered in this way. The body weight was measured every day and the tumor volume was measured every 3 days. After 100 days of observation, the mice were killed, and the tumor tissue was taken to measure the tumor weight and then the tumor volume, tumor volume inhibition rate and tumor inhibition rate were calculated. The morphology of tumor tissues was observed by using HE staining. The protein levels of anti-tumor effect indexes like rasP21, cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), cardiac troponin Ⅰ (cTn-Ⅰ) and brain natriuretic peptide (BNP) in serum of mice were detected by using enzyme linked immunosorbent assay (ELISA).Results:PDX model of mice with colorectal cancer was successfully constructed, and the histological characteristics of the primary tumor in the model were well preserved. During administration, 1 mouse died in the capecitabine high dose group; a slow down in tumor volume growth could be found with the increased dose of capecitabine. There was no statistically significant difference in body weight among 4 groups until all mice were killed ( P > 0.05). The tumor volume and tumor weight in the low, middle and high dose groups were lower than those in the control group (all P < 0.05), and the tumor volume and tumor weight showed an obvious decrease with the increase in dose. The tumor volume inhibition rates of low, middle and high dose groups were 42.61%, 67.61% and 77.27%, respectively, and the tumor inhibition rates were 35.53%, 67.77% and 75.09%, respectively. The serum anti-tumor effect indexes rasP21, COX2 and PGE2 in the middle and high dose groups were decreased compared with those in the control group (all P < 0.05), while cTn-Ⅰ and BNP levels were increased compared with those in the control group (all P < 0.05). Conclusions:The established PDX model of mice with colorectal cancer can better retain the histological characteristics of the original tumor. After treatment of middle and high dose of capecitabine, the tumor inhibition effect is obvious, but the risk of myocardial damage should be noticed.

Objective:To explore the survival status of rectal cancer patients with liver metastasis after receiving different treatments and its influencing factors.Methods:The clinicopathological characteristics, treatment methods and survival of 211 rectal cancer patients with liver metastasis who received different treatments in Shanxi Provincial Cancer Hospital from January 2012 to December 2016 were retrospectively analyzed. Cox proportional hazards regression model was used to analyze the related factors affecting the prognosis of patients.Results:The median overall survival (OS) time of 211 rectal cancer patients with liver metastasis was 19 months (1-115 months), and the 1-, 3- and 5-year OS rates were 66%, 22% and 10%. The OS of rectal cancer patients with metachronous liver metastasis was better than that of rectal cancer patients with simultaneous liver metastasis ( χ2 = 17.225, P < 0.01). The OS of patients with primary tumor resection was better than that of patients without primary tumor resection ( χ2 = 69.54, P < 0.01). Among patients with primary tumor resection, the OS of patients with untreated liver metastasis was worse than that of patients with interventional treatment of liver metastasis ( χ2 = 7.311, P = 0.007). Among the patients without primary tumor resection, the OS of patients with chemotherapy alone was better than that of untreated patients ( χ2 = 4.123, P = 0.042). The OS of patients with primary tumor resection and untreated liver metastasis and patients with primary tumor resection and liver metastasis intervention therapy was better than that of patients with chemotherapy alone (both P < 0.01). The results of Cox regression analysis showed that the differentiation degree of primary tumor, liver metastasis and carbohydrate antigen 199 level at diagnosis were independent factors influencing the survival of rectal cancer patients with liver metastasis (all P < 0.01). Conclusion:For patients with diagnosed rectal cancer, even if there is liver metastasis before surgery, active surgical resection of the primary tumor and local treatment of liver metastasis can still improve the survival.

Objective:To explore the association between statins and colorectal cancer and provide evidence for the prevention of colorectal cancer.Methods:Literatures about statins and colorectal cancer published from January 2000 to January 2020 were retrieved from CNKI, Wanfang data, PubMed and Cochrane Library database. The literatures which met the inclusion criteria were collected, and the Newcastle-Ottawa Scale and Jadad score were used to assess the studies. Meta-analysis was performed with statistical software Revman 5.0 and Stata 12.1.Results:A total of 31 studies, involving more than 1.62 million subjects, were included in the analysis. The case-control study ( RR=0.93, 95% CI: 0.88-0.98), the cohort study ( RR=0.75, 95% CI: 0.63-0.88) and the randomized controlled trial ( RR=0.79, 95% CI: 0.65-0.97) showed moderate protective effect of statins. Using statin <5 years ( RR=0.86, 95% CI: 0.76-0.96), average daily dosage ≥34 mg ( RR=0.81, 95% CI: 0.66-0.98) and lipid-soluble statins ( RR=0.86, 95% CI: 0.74-0.99) also had preventive effect on colorectal cancer; while lovastatin ( RR=1.07, 95% CI: 1.00-1.14) increased the risk of colorectal cancer. Conclusion:Statins have protective effect on colorectal cancer.

Objective:To analyze the expression of miR-30a-5p and miR-211 in colorectal cancer tissues, and to explore the relationships between the expression of miR-30a-5p, miR-211 and the clinicopathological characteristics, prognosis of colorectal cancer.Methods:80 patients with colorectal cancer treated in our hospital from February 2013 to December 2015 were retrospectively analyzed, and colorectal cancer tissues and corresponding adjacent tissues (≥3 cm far from the lesion) were collected during operation. Real-time fluorescence quantitative analysis (qRT-PCR) was used to detect the expression levels of miR-30a-5p and miR-211 in tissues, and the relationships between the expressions of miR-30a-5p, miR-211 and the clinicopathological characteristics, prognosis of colorectal cancer patients were analyzed.Results:The expression levels of miR-30a-5p and miR-122 in colorectal cancer tissues were significantly lower than those in adjacent tissues ( P<0.05). The expression levels of miR-30a-5p and miR-211 were not related to gender, age and location of tumors ( P>0.05), but related to differentiation, size of tumors, degree of invasion, tumor node metastasis (TNM) stage and lymph node metastasis ( P<0.05). There was a positive correlation between the expressions of miR-30a-5p and miR-211 in colorectal cancer ( r=0.337, P<0.05). The 3-year survival rates of the low-expression groups of miR-30a-5p and miR-211 were significantly lower than those of the high-expression groups of miR-30a-5p and miR-211 (all P<0.05). Low differentiation, high TNM stage, lymph node metastasis, low expression of miR-30a-5p and low expression of miR-211 were independent risk factors for poor prognosis of colorectal cancer patients ( P<0.05). Conclusions:The expressions of miR-30a-5p and miR-211 are low in colorectal cancer tissues, both of them are related to the clinicopathological characteristics and prognosis of colorectal cancer, such as the degree of differentiation of tumors, lymph node metastasis and so on, which may play a common role in influencing the occurrence and development of colorectal cancer.

Objective: To investigate the expression of B7H3 and B7H4 in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) in correlation with clinicopathological parameters and patient prognosis. Methods: Immunohistochemistry (IHC) was used to detect the expression of B7H3 and B7H4 protein in 100 cases of T-LBL/ALL(test group) and 30 cases of lymph node reactive hyperplasia (LH) (control group), diagnosed at Shanxi Cancer Hospital from January 2001 to June 2017. Real-time RT-PCR was used to detect the mRNA expression of B7H3 and B7H4 in 50 cases of T-LBL/ALL and 30 cases of LH (control group). Results: There were 79 males,21 females. Immunohistochemical results showed that the expression rates of B7H3 and B7H4 were 23%(23/100) and 54%(54/100), respectively. By real-time RT-PCR, the relative expression of B7H3 mRNA in the T-LBL/ALL group was 2.5 times of that of the LH group. The expression levels of B7H4 mRNA in T-LBL/ALL group and LH group were extremely low.Single factor analysis showed that B7H3 protein expression in T-LBL/ALL group was associated with B symptoms and primary nodal disease (P<0.05). B7H4 protein expression was associated with mediastinal broadening and bone marrow involvement (P<0.05). B7H3 protein, B7H3 mRNA, B7H4 protein expression and IPI score were associated with prognosis (P<0.05), and the combined expression of B7H3 and B7H4 was associated with T-LBL/ALL prognosis (P<0.05). Multivariate Cox regression analysis showed that overexpression of B7H3 mRNA was an independent risk factor for the prognosis of patients with T-LBL/ALL (P<0.05). Conclusion Expression of B7H3 and B7H4 is closely corelated with clinicopathological parameters and prognosis of patients with T-LBL/ALL, suggesting that B7H3 and B7H4 expression play an important role in the development of T-LBL/ALL.

Objective To investigate the expression of B7H3 and B7H4 in T lymphoblastic lymphoma/leukemia (T?LBL/ALL) in correlation with clinicopathological parameters and patient prognosis. Methods Immunohistochemistry (IHC) was used to detect the expression of B7H3 and B7H4 protein in 100 cases of T?LBL/ALL(test group) and 30 cases of lymph node reactive hyperplasia (LH) (control group), diagnosed at Shanxi Cancer Hospital from January 2001 to June 2017. Real?time RT?PCR was used to detect the mRNA expression of B7H3 and B7H4 in 50 cases of T?LBL/ALL and 30 cases of LH (control group). Results There were 79 males,21 females. Immunohistochemical results showed that the expression rates of B7H3 and B7H4 were 23%(23/100) and 54%(54/100), respectively. By real?time RT?PCR, the relative expression of B7H3 mRNA in the T?LBL/ALL group was 2.5 times of that of the LH group. The expression levels of B7H4 mRNA in T?LBL/ALL group and LH group were extremely low.Single factor analysis showed that B7H3 protein expression in T?LBL/ALL group was associated with B symptoms and primary nodal disease (P<0.05). B7H4 protein expression was associated with mediastinal broadening and bone marrow involvement (P<0.05). B7H3 protein, B7H3 mRNA, B7H4 protein expression and IPI score were associated with prognosis (P<0.05), and the combined expression of B7H3 and B7H4 was associated with T?LBL/ALL prognosis (P<0.05). Multivariate Cox regression analysis showed that overexpression of B7H3 mRNA was an independent risk factor for the prognosis of patients with T?LBL/ALL (P<0.05). Conclusion Expression of B7H3 and B7H4 is closely corelated with clinicopathological parameters and prognosis of patients with T?LBL/ALL, suggesting that B7H3 and B7H4 expression play an important role in the development of T?LBL/ALL.

AIM: To explore the influence of Huqi San on the Hedgehog signaling pathway in rats with prehe-patocarcinoma.METHODS: The model of prehepatocarcinoma in the rats was established by a modified solt-farber method.The rats were intragastric administrated with Huqi San solution for 3 d after subtotal hepatectomy.Four weeks after administration of the Huqi San solution, the hepatic damage was observed by histopathological analysis.The protein expression of glutathione S-transferase-π (GST-π), alpha-fetoprotein (AFP), OV6, albumin (ALB) and glioma-associated oncogene homolog 2 (Gli2) was detected by immunohistochemistry and immunofluorescence staining.The expression of Sonic hedgehog (Shh), Smoothened (Smo), Gli2, cyclin D and cyclin E at mRNA and protein levels in the rats was determined by RT-qPCR and Western blot, respectively.The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were assayed using diagnostic kits.RESULTS: Compared with model group, Huqi San decreased the serum levels of ALT, AST and GGT, and alleviated the pathological changes in prehepatocarcinoma rats.Huqi San inhibited the protein expression of GST-π and AFP (P<0.05) in the prehepatocarcinoma rats.Huqi San also promoted the protein expression of OV6 and ALB (P<0.05).Furthermore, Huqi San activated Hedgehog signaling pathway and its downstream targeting molecules such as Shh, Smo, Gli2, cyclin D and cyclin E.In addition, the results in vitro showed that Huqi San may activate Hedgehog signaling pathway and promoted oval cell proliferation.CONCLUSION: Huqi San not only promotes hepatic progenitor cell proliferation, but also induces hepatic progenitor cell differentiation and inhibits prehepatocarcinoma in the rats probably via activating Hedgehog signaling pathway.

Purpose To investigate the mutation status of KRAS and PIK3CA gene in colorectal cancer (CRC) primary lesions and corresponding liver metastasis and its clinical significance.Methods The gene mutations of KRAS and PIK3CA were detected in 58 cases of primary lesions of CRC and corresponding liver metastasis tissue by real-time PCR.Results The mutation rates of KRAS were 31.03％ (18/58) and 25.86％ (15/58) in primary lesions of CRC and corresponding liver metastasis tissue,respectively,in which G12D was most commonly detected.The mutation rates of PIK3CA were 8.62％ (5/58) and 10.34％ (6/58) respectively,in which the most common mutation site was E545K.Only one case carried simultaneously both mutations of KRAS (G12D) and PIK3CA (E545K).The mutation of KRAS and PIK3CA had a good consistency between primary lesions and liver metastasis.Univariate analysis showed that the mutation of KRAS was related to the primary lesion of tumor location,the quantity of metastasis and the types of tumor (P ＜ O.05),PIK3 CA mutation was associated with the synchronous/metachronous liver metastasis and the quantity of metastasis (P ＜ 0.05).Multivariate Cox regression analysis showed that synchronous/metachronous liver metastasis and the mutation of KRAS were influencing factors for prognosis of CRC.The overall survival of patients with CRC who had simultaneous liver metastases was longer than those with heterotopic liver metastases;the overall survival of KRAS wild-type mutant patients was longer than those of mutant patients (P ＜ 0.05).Conclusion The G12D site of KRAS gene has the highest mutation frequency in CRC,KRAS/PIK3CA mutation has a good consistency of the primary lesions of CRC and corresponding liver metastasis.Primary lesions can be as the source of molecular detection.To achieve individualized treatment,we need to reassess the genetic status of metastasis based on the choice of targeted therapy for precision medicine.