[The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer].

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Chito-oligosaccharides and macrophages have synergistic effects on improving ovarian stem cells function by regulating inflammatory factors.

BACKGROUND: Chronic low-grade inflammation and ovarian germline stem cells (OGSCs) aging are important reasons for the decline of ovarian reserve function, resulting in ovarian aging and infertility. Regulation of chronic inflammation is expected to promote the proliferation and differentiation of OGSCs, which will become a key means for maintaining and remodeling ovarian function. Our previous study demonstrated that Chitosan Oligosaccharides (Cos) promoted the OGSCs proliferation and remodelled the ovarian function through improving the secretion of immune related factors,but the mechanism remains unclear, and the role of macrophages, the important source of various inflammatory mediators in the ovary needs to be further studied. In this study, we used the method of macrophages and OGSCs co-culture to observe the effect and mechanism of Cos on OGSCs, and explore what contribution macrophages give during this process. Our finding provides new drug treatment options and methods for the prevention and treatment of premature ovarian failure and infertility. METHODS: We used the method of macrophages and OGSCs co-culture to observe the effect and mechanism of Cos on OGSCs, and explore the important contribution of macrophages in it. The immunohistochemical staining was used to locate the OGSCs in the mouse ovary. Immunofluorescent staining, RT-qPCR and ALP staining were used to identify the OGSCs. CCK-8 and western blot were used to evaluate the OGSCs proliferation. ß-galactosidase(SA-ß-Gal) staining and western blot were used to detect the changing of cyclin-dependent kinase inhibitor 1A(P21), P53, Recombinant Sirtuin 1(SIRT1) and Recombinant Sirtuin 3(SIRT3). The levels of immune factors IL-2, IL-10, TNF-α and TGF-ß were explored by using Western blot and ELISA. RESULTS: We found that Cos promoted OGSCs proliferation in a dose-and time-dependent manner, accompanied by IL-2, TNF-α increase and IL-10, TGF-ß decrease. Mouse monocyte-macrophages Leukemia cells(RAW) can also produce the same effect as Cos. When combined with Cos, it can enhance the proliferative effect of Cos in OGSCs, and further increase IL-2, TNF-α and further decrease IL-10, TGF-ß. The macrophages can enhance the proliferative effect of Cos in OGSCs is also associated with the further increase in IL-2, TNF-α and the further decrease in IL-10, TGF-ß. In this study, we determined that the anti-aging genes SIRT-1 and SIRT-3 protein levels were increased by Cos and RAW respectively, whereas the senescence-associated SA-ß-Gal and aging genes P21 and P53 were decreased. Cos and RAW had a protective effect on OGSCs delaying aging. Furthermore, RAW can further decrease the SA-ß-Gal and aging genes P21 and P53 by Cos, and further increase SIRT1 and SIRT3 protein levels in OGSCs by Cos. CONCLUSION: In conclusion, Cos and macrophages have synergistic effects on improving OGSCs function and delaying ovarian aging by regulating inflammatory factors.

Expression and function of patatin-like phospholipase domain-containing 2 in cleft palate induced by retinoic acid.

Cleft palate is a common maxillofacial congenital malformation, and its mechanism still has not been fully illustrated. Recently, lipid metabolic defects have been observed in cleft palate. Patatin-like phospholipase domain-containing 2 (Pnpla2) is an important lipolytic gene. However, its effect on the formation of cleft palate remains unknown. In this research, we explored the expression of Pnpla2 in the palatal shelves of control mice. We also studied mice with cleft palates induced by retinoic acid and its effect on the embryonic palatal mesenchyme (EPM) cells phenotype. We found that Pnpla2 was expressed in the palatal shelves of both the cleft palate and control mice. Pnpla2 expression was lower in cleft palate mice than in the control mice. Experiments with EPM cells showed that knockdown of Pnpla2 inhibited cell proliferation and migration. In conclusion, Pnpla2 is linked to palatal development. We have indicated that low expression of Pnpla2 affects palatogenesis by inhibiting the proliferation and migration of EPM cells.

[Advances in tumor regression patterns and safe distance of distal resection margin after neoadjuvant therapy for rectal cancer].

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.

TRANSCRIPTOME ANALYSIS REVEALED THE MOLECULAR SIGNATURES OF CISPLATIN-FLUOROURACIL COMBINED CHEMOTHERAPY RESISTANCE IN GASTRIC CANCER.

Gastric cancer (GC) is among the top five malignant tumors worldwide in terms of morbidity and death. Chemotherapy is the primary treatment for unresectable or advanced postoperative GC. Chemotherapy resistance developed against cisplatin-fluorouracil (CF) combined chemotherapy is one of the most common clinical issues in patients with GC, leading to poor prognosis. Two different methods were used to analyze GSE14210, and two gene sets were obtained. The first method involved performing the traditional difference analysis (adjusted p<0.05, |log2FC|>=1) by Network Analyst to obtain gene set 1, followed by conducting gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis on the obtained gene set. The second method involved using iDEP to make the weighted gene co-expression network analysis (WGCNA) and performing GO and KEGG enrichment analysis, to obtain gene set 2. Thereafter, the STRING database and Cytoscape were used to construct Protein-Protein Interaction (PPI) networks, screen core clusters, and hub genes of the two gene sets. Furthermore, the hub genes were verified in GSE14210 by the survival analysis method of the Kaplan-Meier plotter database. Finally, we analyzed the mRNA expression of the hub genes by UALCAN and the protein expression of the same by Human Protein Atlas (HPA). Three real hub genes with the same mRNA expression as that of protein were identified, including CENPB, MTA1, and GCNT3. Finally, we performed single gene GO and KEGG enrichment analyses to explore the possible mechanisms of action of these three genes. The mRNA and protein expressions of CENPB, MTA1, and GCNT3 were upregulated in CF-resistant GC patients, and they were significantly associated with bad overall survival (OS). CENPB, MTA1 and GCNT3 are expected to be biomarkers with promising clinical applications as potential therapeutic targets for patients with refractory GC treated with CF combined chemotherapy.

[Changes of the World Health Organization 2022 classification (5th edition) of salivary glands tumors].

Pathological diagnosis of salivary gland tumors is one of the most challenging areas in all head and neck surgical pathology. The classification of salivary gland tumors was updated in the 5th edition of the World Health Organization Classification of Head and Neck Tumours, most of which were based on their molecular pathological characteristerics. This new classification features a description of several new entitiesamong benign and malignant neoplasms, salivary gland tumors with updated naming or diagnostic criteria, and lesions deleted from this section, etc.This present review focuses on the updates and changes in the new classification of salivary gland tumors, and provides some reference for head and neck surgeons and pathologists.

Postoperative myocardial injury and platelet reactivity in patients undergoing vascular surgery: The platelet reactivity and postoperative myocardial injury after major vascular surgery (PROMISE) study.

BACKGROUND: Postoperative myocardial injury (PMI) after major vascular surgery, detected by elevated cardiac troponin (cTn), has been associated with morbidity and mortality. It is unclear whether the pathophysiology of PMI is determined by increased platelet activity. OBJECTIVE: To examine the relationship between platelet activation (P-selectin expression) and PMI in patients undergoing elective open abdominal aortic surgery. METHODS: This prospective, single-centre, observational, cohort study included 33 patients undergoing elective open abdominal aortic surgery between March 2018 and April 2021. Patients were routinely treated with aspirin. Unstimulated platelet activation was measured by platelet bound P-selectin expression (range 0-100 %). Explorative coagulation measurements were: stimulated platelet aggregation measured with the VerifyNow® assay (aspirin cartridge), with the Multiplate® analyzer (ASPI, ADP and TRAP) and stimulated coagulation status evaluated by the TEG® Hemostasis Analyzer System (global hemostasis cartridge). The primary outcome was cTn release assessed by the fifth generation high-sensitive cTn assay. Multivariable generalized linear mixed models were used to evaluate the association between platelet function and cTn concentrations over time. RESULTS: Ten patients (30.3 %) developed PMI. Increased P-selectin expression directly after surgery was associated with the cTn concentrations over 48 h (ß = 1.39 (1.1-1.75), P = 0.0064). No association was found between P-selectin measured later after surgery (at 24 h or 48 h) and cTn concentrations. Furthermore, there was no association between the explorative coagulation parameters and cTn release. CONCLUSION: Platelet reactivity, assessed by P-selectin expression measured directly after surgery is associated with PMI, assessed by elevated cTn concentrations in the early postoperative period in patients undergoing elective open abdominal aortic surgery.

[The influence of residual astigmatism on the postoperative visual quality in patients with implantation of an extended depth of focus intraocular lens].

Objective: To investigate the influence of residual astigmatism on the postoperative visual acuity in cataract patients with implantation of an extended depth of focus intraocular lens (IOL). Methods: Retrospective cohort study. A total of 56 eyes of 56 cataract patients who underwent phacoemulsification combined with extended depth of focus IOL implantation from January 2019 to December 2020 at Eye & ENT Hospital of Fudan University were included. There were 29 males and 27 females in all patients, and the age was (65±9) years. Patients were divided into two groups according to their postoperative residual astigmatism: low astigmatism group (<0.75 D, 28 eyes) and high astigmatism group (0.75 to 1.50 D, 28 eyes). At 3 months after surgery, measurements were completed, including postoperative uncorrected distance (5 m) visual acuity, uncorrected intermediate (80 cm) visual acuity, uncorrected near (40 cm) visual acuity, best corrected visual acuity (all the visual acuity was converted to the logarithm of the minimum angle of resolution visual acuity), defocus curves, quick contrast sensitivity function, wavefront aberration, and VF-14 questionnaire scores. The independent samples t-test and Mann-Whitney U test were used for data analysis. Results: The low astigmatism group and high astigmatism group's uncorrected distance visual acuity [M (Q1, Q3)] were 0.05 (-0.06, 0.10), 0.08 (0.00, 0.22), their uncorrected intermediate visual acuity were 0.11 (0.00, 0.20), 0.14 (0.10, 0.21), their uncorrected near visual acuity were 0.28 (0.20, 0.32), 0.26 (0.20, 0.30), and their best corrected visual acuity were 0.17 (0.05, 0.30), 0.14 (0.04, 0.22), respectively. The differences were not statistically significant (all P>0.05). No significant difference was found in the defocus curves from +1.00 to -4.00 D, at intervals of +0.50 D, between the two groups (all P>0.05). No significant difference was found in the quick contrast sensitivity of low, middle and high frequency of dark vision between the low astigmatism group and high astigmatism group (all P>0.05), and the area under Log contrast sensitivity function of the two groups were 0.87±0.28 and 0.77±0.30 (P>0.05). The total whole-eye aberrations were 0.59±0.18 and 0.74±0.51, and the total higher-order aberrations were 0.30±0.13 and 0.37±0.25 in the two groups at 4.0-mm pupil diameter. The differences were not statistically significant when the total whole-eye aberration, total higher-order aberration, coma, cloverleaf aberration, and spherical aberration were compared (all P>0.05). The differences of the total VF-14 visual scores, near visual acuity scores and the distance visual acuity scores of the two groups were not statistically significant (all P>0.05). Conclusion: Cataract patients with residual postoperative astigmatism 0.75 to 1.50 D can obtain as good visual quality as those with postoperative residual astigmatism<0.75 D after implantation of an extended depth of focus IOL.

Chitosan Oligosaccharides Alleviate H2O2-stimulated Granulosa Cell Damage via HIF-1α Signaling Pathway.

Oocyte maturation disorder and decreased quality are the main causes of infertility in women, and granulosa cells (GCs) provide the only microenvironment for oocyte maturation through autocrine and paracrine signaling by steroid hormones and growth factors. However, chronic inflammation and oxidative stress caused by ovarian hypoxia are the largest contributors to ovarian aging and GC dysfunction. Therefore, the amelioration of chronic inflammation and oxidative stress is expected to be a pivotal method to improve GC function and oocyte quality. In this study, we detected the protective effect of chitosan oligosaccharides (COS), on hydrogen peroxide- (H2O2-) stimulated oxidative damage in a human ovarian granulosa cell line (KGN). COS significantly increased cell viability, mitochondrial function, and the cellular glutathione (GSH) content and reduced apoptosis, reactive oxygen species (ROS) content, and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial-derived growth factor (VEGF) in H2O2-stimulated KGN cells. COS treatment significantly increased levels of the TGF-ß1 and IL-10 proteins and decreased levels of the IL-6 protein. Compared with H2O2-stimulated KGN cells, COS significantly increased the levels of E2 and P4 and decreased SA-ß-gal protein expression. Furthermore, COS caused significant inactivation of the HIF-1α-VEGF pathway in H2O2-stimulated KGN cells. Moreover, inhibition of this pathway enhanced the inhibitory effects of COS on H2O2-stimulated oxidative injury and apoptosis in GCs. Thus, COS protected GCs from H2O2-stimulated oxidative damage and apoptosis by inactivating the HIF-1α-VEGF signaling pathway. In the future, COS might represent a therapeutic approach for ameliorating disrupted follicle development.

Inhibition of carbonic anhydrase II by sulfonamide derivatives.

A series of sulfonamide derivatives were synthesized, and the enzyme inhibitory activity of the synthesized compounds on carbonic anhydrase II was evaluated. Through molecular docking studies, it was found that compounds 1b, 1e, 2a, 2b, 3a have a strong binding affinity to carbonic anhydrase II. The IC50 values of the four compounds 1e, 2b, 3a, and 3b were lower than that of the positive control drug acetazolamide. What's more, the compounds had a high inhibitory activity for A549 lung cancer cell growth, among them, 1e and 3a could inhibit both carbonic anhydrase II and lung cancer cell proliferation.

Ionic dissolution products of Cerium-doped bioactive glass nanoparticles promote cellular osteogenic differentiation and extracellular matrix formation of human bone marrow derived mesenchymal stromal cells.

Cerium (Ce) is a promising candidate ion for application in bone tissue engineering (BTE) since it reduces the presence of reactive oxygen species. Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) serving as vectors for the local application of Ce already demonstrated stimulating effects on the expression of pro-osteogenic genes in Saos-2 cells. So far, there is no evidence available about the effects of Ce-doped MBGNs on the viability, osteogenic differentiation and the formation of the osseous extracellular matrix (ECM) of primary human bone marrow-derived mesenchymal stromal cells (BMSCs). Therefore, in this study, the biocompatibility of the ionic dissolution products (IDPs) of MBGNs containing increasing concentrations of CeO2(0.05 MCe-MBGNs, composition in mol%: 86.6SiO2-12.1CaO-1.3CeO2; and 0.2 MCe-MBGNs, composition in mol%: 86.0SiO2-11.8CaO-2.2CeO2) and unmodified MBGNs (composition in mol%: 86SiO2-14CaO) was evaluated using human BMSCs. Eventually, the impact of the MBGNs' IDPs on the cellular osteogenic differentiation and their ability to build and mature a primitive osseous ECM was assessed. The Ce-doped MBGNs had a positive influence on the viability and stimulated the cellular osteogenic differentiation of human BMSCs evaluated by analyzing the activity of alkaline phosphate as a marker enzyme for osteoblasts in the present setting. Furthermore, the formation and calcification of a primitive osseous ECM was significantly stimulated in the presence of Ce-doped MBGNs in a positive concentration-dependent manner as demonstrated by an elevated presence of collagen and increased ECM calcification. The results of thisin-vitrostudy show that Ce-doped MBGNs are attractive candidates for further application in BTE.

[Effect of p38MAPK gene silencing on expression of oncogenes and apoptotic genes induced by PM(2.5) in hepatocytes].

Objective: To study the effect of p38 mitogen-activated protein kinase (MAPK) gene silencing on expression of apoptotic genes and oncogenes in hepatocytes treated with PM(2.5). Methods: From June to September 2019, according to the p38MAPK gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, ligated into PLVX-shRNA2-puro after annealing, and the recombinant lentiviral vector was transfected into L02 hepatocytes. The p38MAPK silencing cells were identified by real-time fluorescent quantitative PCR and western blotting. The normal L02 cells and p38MAPK silencing cells were treated with 50 µg/mL PM(2.5) water soluble solution, 10 µmol/L positive control Cr(6+), and a blank control group was set up, the treatment time was 24 h. The mRNA levels of oncogenes (c-fos, c-myc, k-ras) , tumor suppressor gene (p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by Western blotting. Results: The expression levels of p38MAPK mRNA and protein in p38MAPK gene silencing cells were significantly lower than those in L02 hepatocytes (P<0.05) , and the p38MAPK gene silencing cell line was successfully constructed. Compared with the blank control group, the expression levels of the oncogenes c-fos, c-myc, k-ras and the apoptosis genes Caspase-3, Caspase-8 and Caspase-9 increased, the expression level of tumor suppressor gene p53 decreased in the L02 hepatocyte group treated with PM(2.5) water soluble matter, and the differences were statistically significant (P<0.05) . Compared with the L02 hepatocytes group treated with PM(2.5) water soluble matter, the expression levels of the oncogenes c-fos, c-myc, k-ras and apoptosis genes Caspase-3, Caspase-8 and Caspase-9 decreased, the expression level of tumor suppressor gene p53 increased in the p38MAPK gene silencing cells group treated with PM(2.5) water soluble matter, and the differences were statistically significant (P<0.05) . Conclusion: PM(2.5) has effects on the expression of oncogenes, tumor suppressor genes and apoptotic genes in L02 hepatocytes, while p38MAPK gene silencing can inhibit the effects of PM(2.5) on L02 hepatocytes.

[Effect of c-myc gene silence on the expression of oncogenes and apoptotic genes in hepatocytes treated with PM(2).5].

Objective: To construct the c-myc gene silenced hepatocytes, study the effect of c-myc gene silence on expression of oncogenes and apoptosis genes in hepatocytes treated with PM2.5. Methods: According to the c-myc gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, the recombinant lentiviral vector was transfected into L02 hepatocytes. The real-time quantitative PCR and western blotting were used to identify the effect of c-myc gene silencing. L02 cells and c-myc gene silenced cells were used as experimental subjects. The normal L02 cells and c-myc silenced cells were treated with 50 µg/ml PM(2.5) water soluble solution, 10 µM positive control Cr(6+) and a blank control, the treatment period was 24 h. The mRNA levels of oncogenes (c-myc, c-fos, k-ras, p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by western blotting. Results: The mRNA level and protein level of c-myc decreased by 81% and 70% in c-myc silenced cells when compared with the normal L02 hepatocytes, the above results indicate that c-myc gene silenced cells were successfully constructed. After c-myc silenced cells were treated with PM2.5 water soluble solution, The mRNA levels of c-myc, c-fos, and k-ras decreased by 84.1%, 45.4%, and 54.6% (P<0.05) , p53 increased by 192.9% (P<0.05) , and the expression of Caspase-3, Caspase-8, and Caspase-9 decreased by 24.4%, 36.1%, 60.9% (P<0.05) . In the Cr(6+) positive control group, the expression of c-myc, c-fos, and k-ras decreased by 72.1%, 82.2%, and 54.0% (P<0.05) , p53 increased by 250.0% (P<0.05) , the expression of Caspase-3, Caspase-8, and Caspase-9 decreased by 34.6%, 36.0%, 68.9% (P<0.05) , respectively, when compared with the normal L02 hepatocytes (P<0.05) . Western blotting results showed that the protein levels of c-myc and c-fos increased, p53 decreased after PM(2.5) exposure; the protein levels of Caspase-3, Caspase-8, Caspase-9 increased after PM(2.5) exposure (P<0.05) . When in comparison with the c-myc silenced group, the protein levels of c-myc and c-fos decreased, p53 protein increased in PM(2).5 exposed group (P<0.05) . Conclusion: c-myc gene silenced cells were successfully constructed in this paper. PM(2.5) could promote the expression of oncogenes and apoptotic genes in L02 cells, and c-myc gene silencing can inhibit the expression of oncogenes and apoptotic genes after PM(2.5) treatment in L02 cells.

LncRNA LINC00963 promotes proliferation and migration through the miR-124-3p/FZD4 pathway in colorectal cancer.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been identified in various malignant tumors and determined to play an essential role in terms of cancer progression. In this study, we aimed at exploring the molecular mechanism of LINC00963 in colorectal cancer (CRC). PATIENTS AND METHODS: The mRNA expressions of LINC00963, miR-124-3p and FZD4 in CRC tissues and cells were detected by qRT-PCR. CCK-8 and transwell assay were chosen to measure the CRC cell vitality. Western blot analysis was performed to assess the expression level of FZD4 in CRC. The correlation between LINC00963 and miR-124-3p or miR-124-3p and FZD4 was appraised by Dual-Luciferase reporter assay. RESULTS: In this study, LINC00963 was significantly upregulated in CRC tissues and cells. Functionally, LINC00963 knockdown inhibited cell progression in CRC. The results verified that LINC00963 can restrain the expression of miR-124-3p. Moreover, FZD4 restored the inhibitory effect of miR-124-3p on the progression of CRC cells. Besides that, we preliminarily verified that FZD4 was a direct target gene of LINC00963/miR-124-3p axis in CRC. CONCLUSIONS: Our study demonstrated that LINC00963/miR-124-3p/FZD4 played a curial role in cell proliferation and migration in CRC. In addition, LINC00963 can be a possible therapeutic and diagnostic target for CRC treatment.

Retrospective study of the functional and oncological outcomes of conformal sphincter preservation operation in the treatment of very low rectal cancer.

BACKGROUND: Conformal sphincter preservation operation (CSPO) is a new surgical procedure for very low rectal cancers (within 4-5 cm from the anal verge). CSPO preserves more of the dentate line and distal rectal wall and also avoids injuring nerves in the intersphincteric space, resulting in satisfactory anal function after resection. The aim of this study was to analyze the short-term surgical results and long-term oncological and functional outcomes of CSPO. METHODS: Consecutive patients with very low rectal cancer, who had CSPO between January 2011 and October 2018 at Changhai Hospital, Shanghai were included. Patient demographics, clinicopathological features, oncological outcomes and anal function were analyzed. RESULTS: A total of 102 patients (67 men) with a mean age of 56.9 ± 10.8 years were included. The median distance of the tumor from the anal verge was 3 (IQR, 3-4) cm. Thirty-five patients received neoadjuvant chemoradiation (nCRT). The median distal resection margin (DRM) was 0.5 (IQR, 0.3-0.8) cm. One patient had a positive DRM. All circumferential margins were negative. There was no perioperative mortality. The postoperative complication rate was 19.6%. The median duration of follow-up was 28 (IQR, 12-45.5) months. The local recurrence rate was 2% and distant metastasis rate was 10.8%. The 3-year overall survival and disease-free survival rates were 100% and 83.9%, respectively. The mean Wexner incontinence and low anterior resection syndrome scores 12 months after ileostomy reversal were 5.9 ± 4.3, and 29.2 ± 6.9, respectively. CONCLUSIONS: For patients with very low rectal cancers, fecal continence can be preserved with CSPO without compromising oncological results.

LINC01857 promotes the development of gastric cancer by regulating microRNA-200b.

OBJECTIVE: The aim of this study was to investigate the expression characteristics of LINC01857 in gastric cancer (GCa), and to further study whether it could promote GCa development by modulating microRNA-200b. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine LINC01857 expression in 60 pairs of GCa tissues and adjacent tissues. The interplay between LINC01857 level and clinical indexes and the prognosis of GCa patients was analyzed. Meanwhile, qRT-PCR was used to verify the expression level of LINC01857 in GCa cell lines. LINC01857 knockdown model was constructed by lentivirus transfection in GCa cell lines. Subsequently, the effect of LINC01857 on the biological function of GCa cells was analyzed by Cell Counting Kit 8 (CCK8), wound healing, and transwell assays. Furthermore, the in-depth relationship between LINC01857 and microRNA-200b was explored. RESULTS: QRT-PCR results showed that LINC01857 level in GCa tissues was remarkably higher than that of adjacent tissues, and the difference was statistically significant (p<0.05). Compared with patients with a low level of LINC01857, the rate of lymph node and distant metastasis in patients with a high level of LINC01857 was remarkably higher, while the overall survival rate was lower (p<0.05). In vitro experiments showed that LINC01857 knockdown remarkably decreased the invasion, migration, and crawling ability of GCa cells (p<0.05). Subsequent qRT-PCR results demonstrated that the level of microRNA-200b was remarkably upregulated after the silence of LINC01857. In addition, the silence of microRNA-200b could reverse the biological function of GCa cells induced by the knockout of LINC01857. CONCLUSIONS: LINC01857 was highly expressed in GCa, and was associated with lymph node metastasis, distant metastasis, and poor prognosis of patients with GCa. In addition, LINC01857 enhanced the metastatic ability of GCa cells by regulating microRNA-200b.

[The 476th case: skin rash, edema, thrombocytopenia and anemia].

The 21-year-old male patient was admitted to the Department of Rheumatology and Immunology at Peking Union Medical College Hospital with chief complaints of "skin rash for 1 year and edema for 2 months". He was diagnosed with systemic lupus erythematosus (SLE) with renal, cardiac and hematological involvement. Remission was not achieved after glucocorticoid pulse treatment. The patient experienced oliguria, malignant hypertension, accompanied by thrombocytopenia and low serum complements, and elevated lactate dehydrogenase and serum creatinine. Schistocytes were seen in the peripheral blood smear. Thrombotic microangiopathy (TMA) secondary to SLE was diagnosed. Though plasma exchange was partially effective, TMA could not be controlled yet. The activity of serum von Willebrand factor -cleaving protease (ADAMTS 13) was 100%, and ADAMTS 13 inhibitor was negative. Finally, remission of the disease was achieved after second glucocorticoid pulse therapy and rituximab treatment. At the 3-month follow-up, the patient's condition was stable with mild anemia and normal platelet count. Patients with TMA secondary to SLE are heterogenous, while normal ADAMT 13 activity indicates poor prognosis. Early and aggressive treatment is important for disease control, and plasma exchange is helpful as a supportive care.

PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD.

AIM: We aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. MATERIALS AND METHODS: We enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a 'strict-normal' TSH group (TSH level 0.4 to 2.5mIU/L; n=283) and a 'high-normal' TSH group (TSH level 2.5 to 5.3mIU/L with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes. RESULTS: Compared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298-8.284; P=0.012). CONCLUSION: In euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.