Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.
Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Colorectal Neoplasms/pathology* ; Indoles/therapeutic use* ; Irinotecan/therapeutic use* ; Prospective Studies

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

OBJECTIVE: Traditional epidemiological studies have shown that C-reactive protein (CRP) is associated with the risk of cardiovascular diseases (CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization (MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure. METHODS: We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken (JENGER), and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables. MR estimates were calculated with the inverse-variance weighted (IVW), penalized weighted median and weighted median. MR-Egger regression was used to explore pleiotropy. RESULTS: No significant causal association of genetically determined CRP level with ischemic stroke, atrial fibrillation or arrhythmia was found with all four MR methods (all Ps > 0.05). The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure ( OR: 1.337, 95% CI: 1.005-1.780, P = 0.046), whereas the other three methods did not. No clear pleiotropy or heterogeneity were observed. CONCLUSIONS Suggestive evidence was found only in analysis of congestive heart failure; therefore, further studies are necessary. Furthermore, no causal association was found between CRP and the other three cardiovascular outcomes.
C-Reactive Protein/metabolism* ; Cardiovascular Diseases/metabolism* ; Genetic Predisposition to Disease ; Genotype ; Humans ; Japan ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Risk Factors

Objective:To construct the targeting evaluation method of traditional Chinese medicine （TCM） preparations based on supramolecular Qi chromatography theory， and to study the liver targeting effect of Bupleuri Radix on Pien Tze Huang. Method:The molecular connectivity index （MCI） was used to analyze the characteristics of imprinted template and liver targeting tendency of TCM mainly attributed to liver meridian and components of Pien Tze Huang， and combined with target dynamics and total statistical moment principle， aimed at the independent action characteristics of multi-component imprinted template of TCM， a method for evaluating the targeting of TCM preparations was established. Hepatoma rats in Pien Tze Huang group， Bupleuri Radix group， Pien Tze Huang+Bupleuri Radix group and blank group were tested and verified. Result:After the average value of MCI of TCM mainly attributed to liver meridian was deducted， the MCI similarity between Pien Tze Huang group and Bupleuri Radix group was 0.376 8， Pien Tze Huang+Bupleuri Radix group and Bupleuri Radix group was 0.988 2， so it was predicted that Bupleuri Radix could enhance the liver targeting of Pien Tze Huang. A system for evaluating the targeting of TCM compounds was established， including relative total uptake efficiency （RUE_T）， relative total concentration （RC_T）， relative imprinted tendency （RIT_T） and relative imprinted variance （RIV_T）. The RUE_T and RC_T of liver were the highest in all tissues （RUE_T=1.88>1，RC_T=2.30>1）， and the corresponding values of other tissues were all <1， indicating that Pien Tze Huang combined with Bupleuri Radix could increase its distribution in liver and enhance liver targeting. Except for plasma， the RIT_T and RIV_T of other tissues fluctuated around 1.0， indicating that targeted modification did not change imprinted tendency of Pien Tze Huang and had no significant effect on the types of components. Conclusion:Under the guidance of supramolecular Qi chromatography theory， a targeting evaluation parameter system can be established to characterize the multi-component imprinted effect of TCM preparations by MCI and total statistical moment parameters， so as to realize the evaluation of targeting of TCM preparations. The addition of Bupleuri Radix can increase the liver targeting of Pien Tze Huang.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

COVID-19/genetics* ; Genetic Predisposition to Disease ; Humans ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Risk Factors ; SARS-CoV-2 ; Vitamin D/blood*

OBJECTIVE: To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC). METHODS: We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries. RESULTS: Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups. CONCLUSION CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.
Carcinoma, Transitional Cell ; Humans ; Nephrectomy ; Nephroureterectomy ; Retrospective Studies ; Treatment Outcome ; Urologic Neoplasms

Objective To compare the effect of laparoscopic and open surgery in treatment of rectal cancer. Methods 80 cases of patients with rectal cancer from May 2008 to May 2013 were selected, they were randomly divided into laparoscopy surgery group (n = 40) and open surgery group (n = 40), the operation time, intraoperative blood loss, length of incision, lymph node dissection, number for the first time, ventilation time, ambulation time, hospitalization time, cost of hospitalization, postoperative complications, treatment satisfaction of the two groups were statistically analyzed. Results The operation time of the laparoscopic surgery group was significantly longer (P < 0.05), the amount of bleeding was significantly less (P < 0.05), the incision length was significantly shorter (P < 0.05), the first time, ventilation time, ambulation time, hospitalization time were significantly shorter (P < 0.05), the hospitalization cost was significantly higher (P < 0.05), the rate of postoperative complications 15.0% (6/40) was significantly lower than the open surgery group 35.0% (14/40) (P < 0.05) 97.5% (39/40), the treatment satisfaction was significantly higher than the open surgery group 67.5% (27/40)(P < 0.05). Conclusion The effect of laparoscopic and open surgery in treatment of rectal cancer is better than open surgery.

Objectives: To explore the relationship between body fat indexes and hypertension levels by quantitative CT (QCT) study. Methods: A total of 1488 participants from "prospective urban-rural epidemiology (PURE) study" were enrolled. The participants' age were from 42 to 82 years; based on blood pressure (BP) they were divided into 2 groups: Non-hypertension group, n=783 and Hypertension group, n=705. QCT fat measurement software was used to examine L2 level abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT); body mass index (BMI), waist circumferences (WC), hip circumferences (HC) and waist-to-height ratio (WHtR) were measured and calculated; liner Logistic regression analysis and 2-classified Logistic analysis were conducted to study the relationships between hypertension and anthropometric indices, abdominal VAT, SAT respectively. Results: Compared with Non-hypertension group, Hypertension group had increased BMI, WC, HC, WHtR, abdominal VAT and SAT, P<0.05. BMI, WC, HC, WHtR, abdominal VAT and SAT were related to both systolic BP (SBP) and diastolic BP (DBP), P<0.05. Multivariable Logistic regression analysis indicated that WHtR, abdominal VAT, SAT were the independent impact factors of SBP and WC, abdominal VAT were the independent impact factors of DBP; further investigation showed that abdominal VAT and WC were the independent impact factors of hypertension. Conclusions: Abdominal VAT was robustly related to hypertension in Chinese population, it might be helpful for risk stratification in hypertension patients.

Several studies have demonstrated an association between physical activity and telomere length; however, the association remains inconsistent. A cross-sectional study consisting of 588 participants (375 females, median age of 33.8 years) was carried out to investigate the association between telomere length and physical activity in a general population from North China. The results show that relative telomere length is not significantly different in participants in the northern Chinese population with different levels of physical activity, either in the model only adjusted for age (F = 2.127, P = 0.120) or in the model adjusted for demographics and lifestyle (F = 1.227, P = 0.294). The gender-stratified analysis also produced insignificant results. Our study confirmed a non-significant association between physical activity and telomere length in the northern Chinese population, which adds to the inconsistent association between physical activity and telomere length across different ethnic populations.
Adult ; Asian Continental Ancestry Group ; genetics ; China ; Cohort Studies ; Cross-Sectional Studies ; Exercise ; physiology ; Female ; Humans ; Male ; Middle Aged ; Telomere ; Young Adult