Objective:To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis.Methods:The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ 2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result:Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III–IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ 2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ 2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ 2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ 2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ 2=6.293, P=0.043). The proportions of TNM Stage III–IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ 2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ 2=13.994, P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ 2=10.457, P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ 2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ 2=5.086, P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ 2=19.791, P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ 2=4.601, P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ 2=11.996, P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ 2=7.643, P=0.006), had a higher proportion of TNM Stage III–IV disease (60.2% [100/166] vs. 24.2% [8/33], χ 2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ 2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively ( P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS ( P=0.026). Conclusions:Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Objective:To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis.Methods:The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ 2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result:Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III–IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ 2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ 2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ 2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ 2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ 2=6.293, P=0.043). The proportions of TNM Stage III–IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ 2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ 2=13.994, P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ 2=10.457, P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ 2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ 2=5.086, P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ 2=19.791, P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ 2=4.601, P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ 2=11.996, P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ 2=7.643, P=0.006), had a higher proportion of TNM Stage III–IV disease (60.2% [100/166] vs. 24.2% [8/33], χ 2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ 2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively ( P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS ( P=0.026). Conclusions:Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Objective    To investigate the value of chest high-resolution computed tomography (HRCT) score in evaluating the severity of hip fracture-induced early acute lung injury (ALI) in the elderly patients. Methods    The clinical data of 289 elderly hip fracture patients in Chongqing Traditional Chinese Medicine Hospital from July 2014 to April 2020 were retrospectively analyzed. All patients were divided into two groups, including an ALI group (n=114, 36 males and 78 females at age of 82.94±6.85 years) and a non-ALI group (n=175, 51 males and 124 females at age of 84.42±6.31 years). General information, chest HRCT scores and PaO2/FiO2 were compared between the two groups. Correlation analysis was used to compare the relationship between chest HRCT scores and PaO2/FiO2. Multiple linear stepwise regression analysis was applied to evaluate the effective extent of the diffuse ground glass opacity (DGGO), intense parenchymal opacification (IPO), and reticulation HRCT scores to the overall HRCT scores. Results    The DGGO scores, IPO scores, reticulation scores, overall HRCT scores and PaO2/FiO2 were higher in the ALI group than those in the non-ALI group (P<0.001). In the ALI group, correlation analysis showed that DGGO, overall HRCT scores were in significantly negative correlation with PaO2/FiO2 (P<0.001). In addition, the correlation among PaO2/FiO2 and overall HRCT scores was more significant than that of DGGO scores. Multiple stepwise regression analysis indicated that DGGO, IPO, and reticulation scores were independent influencing factors for overall HRCT scores. Among the influencing factors, DGGO scores had the greatest impact, then IPO scores and reticulation scores. The HRCT signs of DGGO, IPO, and reticulation appeared simultaneously had the greatest effects on the overall HRCT scores. Conclusion    The chest HRCT score, which is associated with PaO2/FiO2, also can be used in the severity assessment of elderly patients with early ALI caused by hip fracture.

Objective To establish the blood Septin9 methylation detection system for early screening of colorectal cancer based on fluorescence PCR technology .Methods The PCR primer of Septin9 was designed by searching the CpG island site of Septin9 methylation in the NCBI database .The high methylation site of Septin9 gene promoter region was confirmed by PCR amplification and sequencing after extracting DNA from colorectal cancer and para-carcinoma tissues .The fluorescence PCR and TaqMan probe detection technique was designed by aiming at high methylation site for constructing the plasma sample methylation detection sys-tem .Then its accuracy ,specificity ,repeatability and minimum detectable amount were performed the assess-ment and analysis .The SETP9 methylation detection was performed in plasma samples from 57 cases of color-ectal cancer and 30 healthy persons .Results The high methylation site of Septin9 gene in tissue samples was confirmed by sequencing .This site served as the target for designing fluorescence PCR detection system .After assessment ,the accuracy ,specificity and repeatability of this detection system were 100％ ,the lowest detection amount reached 0 .1 ng/μL .Among the plasma samples in 57 cases of colorectal cancer ,the positive rate of Septin9 methylation site detection was 71 .92％ (41/57) and the positive rate of in the patients with pathologi-cal stage Ⅰ and Ⅱ of colorectal cancer reached 64 .2％ .But Septin9 gene had no methylation in plasma of healthy population .Conclusion The plasma fluorescence PCR detection system with Septin9 gene methylation as the target has the characteristics of high sensitivity ,high specificity and high accuracy ,which is the reliable detection technique for the early screening of colorectal cancer and has good clinical application prospect .

Objective To investigate the expressions of P53,topoisomeraseⅡ(TopoⅡ)and multidrug resistance associated protein(MRP)in tissues of colorectal cancer of patients combined with chronic schistosomiasis.Method The retrospective case-control study was adopted.The clinicopathological data of 338 colorectal cancer patients who were admitted to the Zhejiang Cancer Hospital between January 2008 and December 2010 were collected.Cancer tissue specimens from surgical resection were collected.Among 338 patients,80 were combined with chronic schistosomiasis and 258 were combined with non-chronic schistosomiasis.The expressions of P53,TopoⅡand MRP were dectected using immunohistochemistry(IHC).Ranked data were presented as percentage and analyzed using the non-parametric test.Results The negative,weak positive,positive and strong positive expressions of P53 were respectively 5.00％(4/80),87.50％(70/80),3.75％(3/80),3.75％(3/80)in tissues of colorectal cancer of patients combined with chronic schistosomiasis and 28.68％(74/258),19.38％(50/258),16.67％(43/258),35.27％(91/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with a statistically significant difference(Z=-2.962,P＜0.05).The negative,weak positive,positive and strong positive expressions of TopoⅡwere respectively 8.75％(7/80),51.25％(41/80),22.50％(18/80),17.50％(14/80)in tissues of colorectal cancer of patients combined with chronic schistosomiasis and 12.01％(31/258),55.43％(143/258),22.48％(58/258),10.08％(26/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with no statistically significant difference(Z=-1.551,P＞0.05).The negative,weak positive,positive and strong positive expressions of MRP were respectively 7.50％(6/80),40.00％(32/80),28.75％(23/80),23.75％(19/80)in issues of colorectal cancer of patients combined with chronic schistosomiasis and 24.42％(63/258),38.37％(99/258),24.03％(62/258),13.18％(34/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with a statistically significant difference(Z=-3.408,P＜0.05).Conclusion There are abnormal expressions of P53 and MRP in tissues of colorectal cancer of patients combined with chronic schistosomiasis,which may be involved in the hypothetical mechanism of chronic schistosomiasis inducing carcinogenesis of colorectal cancer.

Aim To investigate the anti-neuroinflam-matory activities of dehydromiltirone and the underlying mechanisms in LPS-stimulated microglial cell line BV2 cells. Methods BV2 cells were pre-treated with de-hydromiltirone, then stimulated by LPS. The levels of nitric oxide( NO) were measured by Griess assay, and the concentrations of pro-inflammatory cytokines were measured by ELISA assay. Confocal fluorescence mi-croscopy was used to measure the expression of MAC-1, the biomarker of activated BV2 cells. The levels of-inducible nitric oxide synthase ( iNOS ) , cyclooxygen-ase-2 ( COX-2 ) , NF-κB and PI3 K/Akt were deter-mined by Western blot analysis. Results The treat-ment of dehydromiltirone significantly inhibited the pro-duction of NO, TNF-α and IL-6, attenuated the ex-pression of iNOS and COX-2 protein, and dampened the microglial activation in LPS-stimulated BV2 cells. The mechanistic study revealed that dehydromiltirone inhibited the phosphorylation of PI3 K and Akt in LPS-stimulated BV2 cells, and decreased NF-κB activation by suppressing the degradation of IκB. Conclusion dehydromiltirone shows significant anti-neuroinflamma-tory effects through inhibiting PI3 K/Akt phosphoryla-tion and then inhibiting NF-κB signaling pathway.

OBJECTIVETo investigate the expression difference of DNA mismatch repair gene hMLH1 and hMSH2 between schistosomiasis-associated colorectal cancer and sporadic colorectal cancer.

METHODClinical and pathological data of colorectal cancer patients receiving operations in Zhejiang Cancer Hospital between January 2008 and December 2010 were retrospectively analyzed. Patients were divided into schistosomiasis group(n=80) and sporadic group (n=258) according to the preoperative history and pathologic results. Pathological specimens were collected and tissue chips were made to analyze the expression of hMLH1 and hMSH2 by immunohistochemistr.

RESULTSCompared with sporadic group, older age [(62.2 ± 9.6) year vs. (57.2 ± 11.7) year, P=0.000)], lower platelet level [(197.0 ± 59.6) × 10(9)/L vs. (217.0 ± 84.3) × 10(9)/L, P=0.02] and lower WBC level [(5.9 ± 1.9) × 10(9)/L vs. (6.6 ± 2.8) × 10(9)/L, P=0.02] were found in schistosomiasis group. Ratio of low differentiation-undifferentiation tumor was significantly higher in schistosomiasis group [44.2% (34/77) vs. 4.9% (12/247), P<0.05]. Lower positive rate of hMLH1 expression [77.5% (62/80) vs. 98.1% (253/258), P=0.000] and hMSH2 expression [75.0% (60/80) vs. 95.3% (246/258), P=0.000] was found in schistosomiasis group compared with sporadic group. Concurrent schistosomiasis was one of the risk factors of hMLH1/hMSH2 deficiency (RR: 0.913, 95% CI: 0.836-0.997, P=0.043), but not an independent factor (RR: 0.951, 95% CI: 0.867-1.043, P=0.286).

CONCLUSIONSchistosomiasis is associated with lower positive expression of hMLH1 and hMSH2, which indicates that hMLH1/hMSH2 deficiency may be a potential mechanism of schistosomiasis inducing carcinogenesis of colorectal cancer.

Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA.

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. C(max), t(1/2), AUC(0-30h) and AUC(0-infinity) were 16.1 +/- 2.7 g/ml, 7.6 +/- 1.2 h, 71.3 +/- 8.8 microg.h/ml and 82.3 +/- 9.5 microg.h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 +/- 2.5 microg/ml at 4 h. The AUC(0-30h) and AUC(0-infinity) were 32.2 +/- 6.2 microg.h/ml and 41.6 +/- 7.2 microg.h/ml, respectively. It representing ~50.6% of the absolute bioavailability.
Administration, Rectal* ; Biological Availability ; Chromatography, High Pressure Liquid ; Fluorescence ; Pharmacokinetics ; Plasma ; Rabbits

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. C(max), t(1/2), AUC(0-30h) and AUC(0-infinity) were 16.1 +/- 2.7 g/ml, 7.6 +/- 1.2 h, 71.3 +/- 8.8 microg.h/ml and 82.3 +/- 9.5 microg.h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 +/- 2.5 microg/ml at 4 h. The AUC(0-30h) and AUC(0-infinity) were 32.2 +/- 6.2 microg.h/ml and 41.6 +/- 7.2 microg.h/ml, respectively. It representing ~50.6% of the absolute bioavailability.
Administration, Rectal* ; Biological Availability ; Chromatography, High Pressure Liquid ; Fluorescence ; Pharmacokinetics ; Plasma ; Rabbits