Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).

hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1-mediated THBS1 transcription.

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.

Self-Assembly of Epitope-Tagged Proteins and Antibodies for Delivering Biologics to Antigen Presenting Cells.

Inspired by the immune system's own strategy for macrophage activation, we describe here a simple self-assembly strategy for generating artificial immune complexes. The built-in recognition domains in the antibody, viz. the Fab and Fc domains, are judiciously leveraged for cargo conjugation to generate the nanoassembly and macrophage targeting, respectively. A responsive linker is engineered into the nanoassembly for releasing the protein cargo inside the macrophages, while ensuring stability during delivery. The design principles are simple and versatile to be applicable to a range of biologics, from small protein toxins to large enzymes, with high loading capacity. This self-assembly platform has the potential for delivering biologics to immune cells with implications in immunotherapy.

A slow feature analysis approach for the optimization of collective variables.

Molecular dynamics simulations have become increasingly important in understanding the microscopic mechanisms of various molecular systems. However, the high energy barriers in complicated molecules often make it difficult to observe events of interest within a reasonable timescale. To address this issue, researchers have developed a variety of enhanced sampling methods to explore configuration space by adding bias potentials along the slowly changing collective variables (CVs). In this study, we have developed a new tool that combines slow feature analysis and biasing-enhanced sampling methods to identify effective CVs and enhance the sampling efficiency of configuration space. We have demonstrated the effectiveness of this tool through three general examples.

CA19­9 is a significant prognostic factor in stage III gastric cancer patients undergoing radical gastrectomy.

BACKGROUND: Due to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 - 9 (CA19-9) and carbohydrate antigen 72 - 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy. METHODS: A total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan-Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients. RESULTS: Among patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS. CONCLUSION: Preoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.

hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma.

BACKGROUND: Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarification. METHODS: RNA sequencing analysis was applied to identify the differentially expressed circRNAs. qRT-PCR was conducted to confirm the expression of hsa_circ_0007919, and CCK-8, FCM, single-cell gel electrophoresis and IF assays were used to analyze the proliferation, apoptosis and gemcitabine (GEM) resistance of pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor growth and DNA damage in vivo. RNA sequencing and GSEA were applied to confirm the downstream genes and pathways of hsa_circ_0007919. FISH and nuclear-cytoplasmic RNA fractionation experiments were conducted to identify the cellular localization of hsa_circ_0007919. ChIRP, RIP, Co-IP, ChIP, MS-PCR and luciferase reporter assays were conducted to confirm the interaction among hsa_circ_0007919, FOXA1, TET1 and the LIG1 promoter. RESULTS: We identified a highly expressed circRNA, hsa_circ_0007919, in GEM-resistant PDAC tissues and cells. High expression of hsa_circ_0007919 correlates with poor overall survival (OS) and disease-free survival (DFS) of PDAC patients. Hsa_circ_0007919 inhibits the DNA damage, accumulation of DNA breaks and apoptosis induced by GEM in a LIG1-dependent manner to maintain cell survival. Mechanistically, hsa_circ_0007919 recruits FOXA1 and TET1 to decrease the methylation of the LIG1 promoter and increase its transcription, further promoting base excision repair, mismatch repair and nucleotide excision repair. At last, we found that GEM enhanced the binding of QKI to the introns of hsa_circ_0007919 pre-mRNA and the splicing and circularization of this pre-mRNA to generate hsa_circ_0007919. CONCLUSIONS: Hsa_circ_0007919 promotes GEM resistance by enhancing DNA damage repair in a LIG1-dependent manner to maintain cell survival. Targeting hsa_circ_0007919 and DNA damage repair pathways could be a therapeutic strategy for PDAC.

Mesoscopic Model for Disjoining Pressure Effects in Nanoscale Thin Liquid Films and Evaporating Extended Meniscuses.

Disjoining pressure effect is the key to describe contact line dynamics, micro/nanoscale liquid-vapor phase change heat transfer, and liquid transport in nanopores. In this paper, by combining a mesoscopic approach for nanoscale liquid-vapor interfacial transport and a mean-field approximation of the long-range solid-fluid molecular interaction, a mesoscopic model for the disjoining pressure effect in nanoscale thin liquid films is proposed. The capability of this model to delineate the disjoining pressure effect is validated. We demonstrate that the Hamaker constant determined from our model agrees very well with molecular dynamics (MD) simulation and that the transient evaporation/condensation mass flux predicted by this mesoscopic model is also consistent with the kinetic theory. Using this model, we investigate the characteristics of the evaporating extended meniscus in a nanochannel. The nonevaporating film region, the evaporating thin-film region, and the intrinsic meniscus region are successfully captured by our model. Our results suggest that the apparent contact angle and thickness of the nonevaporating liquid film are self-tuned according to the evaporation rate, and a higher evaporation rate results a in larger apparent contact angle and thinner nonevaporating liquid film. We also show that disjoining pressure plays a dominant role in the nonevaporating film region and suppresses the evaporation in this region, while capillary pressure dominates the intrinsic meniscus region. Strong evaporation takes place in the thin-film region, and both the disjoining pressure and capillary pressure contribute to the total pressure difference that delivers the liquid from the intrinsic meniscus region to the evaporating thin-film region, compensating for the liquid mass loss due to strong evaporation. Our work provides a new avenue for investigating thin liquid film spreading, liquid transport in nanopores, and microscopic liquid-vapor phase change heat/mass transfer mechanisms near the three-phase contact line region.

Size Ranges of Effective Nucleation Cavities on Gas-Evolving Surfaces.

Bubble nucleation has a significant influence on mass transfer and energy conversion in electrochemical gas-evolving reactions. In this work, we establish a theoretical model for bubble nucleation from gas cavities on gas-evolving surfaces. Based on analyses of transient gas diffusion within the concentration boundary layer and supersaturation equation for stable bubble nuclei, we determined the size ranges of effective nucleation cavities on gas-evolving surfaces under different levels of supersaturation conditions. In addition, a criterion for the incipience of bubble nucleation on gas-evolving surfaces is proposed. We investigate the effects of the contact angle, cone angle, concentration boundary layer thickness, ambient pressure, and temperature on the size ranges of effective nucleation cavities, respectively. We demonstrate that a larger contact angle or a smaller cone angle can broaden the size range of effective cavities, thereby promoting bubble nucleation from cavities. We also show that increasing the concentration boundary layer thickness causes larger cavities to become effective nucleation sites, which significantly expands the size range of effective cavities. In contrast, increasing the ambient pressure enables smaller cavities to become effective nucleation sites, resulting in an expansion in the size range of effective cavities. Results of this work will contribute to the manipulation of bubble nucleation densities and the optimal design of gas-evolving electrodes in various electrochemical gas-evolving reactions.

A highly effective "naked eye" colorimetric and fluorimetric curcumin-based fluorescent sensor for specific and sensitive detection of H2O2in vivo and in vitro.

Hydrogen peroxide (H2O2) is involved in many important tasks in normal cell metabolism and signaling. However, abnormal levels of H2O2 are associated with the occurrence of several diseases. Therefore, it is important to develop a new method for the detection of H2O2in vivo and in vitro. A turn-off sensor, 2,2-difluoro-4,6-bis(3-methoxy-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)styryl)-2H-1,3,2-dioxaborine (DFCB), based on curcumin was developed for the detection of H2O2. The DFCB, an orange-emitting sensor, was constructed by employing 2,2-difluoro-4,6-bis(4-hydroxy-3-methoxystyryl)-2H-1,3,2-dioxaborine (DFC) as the main carrier, and 2-(4-bromomethylphenyl)-4,4,5,5-tetramethyl-1,3,2-doxaborolane as the recognition site. The recognition group on the DFCB sensor could be completely cleaved by H2O2 to generate the intermediate DFC, which would lead to a colorimetric change from bright orange to light blue accompanying by a significantly quenched fluorescence, which could be seen by the naked eye. This sensor exhibited a highly specific fluorescence response to H2O2, in preference to other relevant species, with an excellent anti-interference performance. The sensor DFCB also possessed some advantages including a wide pH response range (6-11), a broad linear range (0-300 µM), and a low detection limit (1.31 µM). The sensing mechanism of the DFCB sensor for H2O2 was verified by HRMS analysis, 1H-NMR titration and DFT calculations. In addition, the use of the DFCB sensor was compatible with the fluorescence imaging of H2O2 in living cells and zebrafish.

LINC01615 maintains cell survival in adaptation to nutrient starvation through the pentose phosphate pathway and modulates chemosensitivity in colorectal cancer.

Numerous mechanisms involved in promoting cancer cell survival under nutrient starvation have been described. Long noncoding RNAs (lncRNAs) have emerged as critical players in colorectal cancer (CRC) progression, but the role of lncRNAs in the progression of CRC under nutrient starvation has not been well clarified. Here, we identified a lncRNA, LINC01615, that was significantly upregulated in response to serum starvation. LINC01615 can contribute to the adaptation of CRC cells to serum-deprived conditions and enhance cell survival under similar conditions. LINC01615 activated the pentose phosphate pathway (PPP) under serum starvation, manifested as decreased ROS production and enhanced nucleotide and lipid synthesis. Glucose-6-phosphate dehydrogenase (G6PD) is a key rate-limiting enzyme of the PPP, and LINC01615 promoted G6PD expression by competitively binding with hnRNPA1 and facilitating G6PD pre-mRNA splicing. Moreover, we also found that serum starvation led to METTL3 degradation by inducing autophagy, which further increased the stability and level of LINC01615 in a m6A-dependent manner. LINC01615 knockdown combined with oxaliplatin achieved remarkable antitumor effects in PDO and PDX models. Collectively, our results demonstrated a novel adaptive survival mechanism permitting tumor cells to survive under limiting nutrient supplies and provided a potential therapeutic target for CRC.

Topoisomerase II dysfunction causes metaphase I arrest by activating Aurora B, SAC and MPF and prevents PB1 abscission in mouse oocytes†.

Oocyte aneuploidy is caused mainly by chromosome nondisjunction and/or unbalanced sister chromatid pre-division. Although studies in somatic cells have shown that topoisomerase II (TOP2) plays important roles in chromosome condensation and timely separation of centromeres, little is known about its role during oocyte meiosis. Furthermore, because VP-16, which is a TOP2 inhibitor and induces DNA double strand breaks, is often used for ovarian cancer chemotherapy, its effects on oocytes must be studied for ovarian cancer patients to recover ovarian function following chemotherapy. This study showed that inhibiting TOP2 with either ICRF-193 or VP-16 during meiosis I impaired chromatin condensation, chromosome alignment, TOP2α localization, and caused metaphase I (MI) arrest and first polar body (PB1) abscission failure. Inhibiting or neutralizing either spindle assembly checkpoint (SAC), Aurora B or maturation-promoting factor (MPF) significantly abolished the effect of ICRF-193 or VP-16 on MI arrest. Treatment with ICRF-193 or VP-16 significantly activated MPF and SAC but the effect disappeared when Aurora B was inhibited. Most of the oocytes matured in the presence of ICRF-193 or VP-16 were arrested at MI, and only 11-27% showed PB1 protrusion. Furthermore, most of the PB1 protrusions formed in the presence of ICRF-193 or VP-16 were retracted after further culture for 7 h. In conclusion, TOP2 dysfunction causes MI arrest by activating Aurora B, SAC, and MPF, and it prevents PB1 abscission by promoting chromatin bridges.

Expression profiling and function analysis identified new microRNAs regulating cumulus expansion and apoptosis in cumulus cells.

Although microRNAs (miRNAs) expressed in cumulus cells (CCs) may be used to select competent oocytes/embryos, only a limited number of such miRNAs has been reported. To identify more miRNAs that regulate cumulus expansion (CE) and CC apoptosis, we first established that mouse cumulus-oocyte complexes (COCs) cultured in expansion-supporting medium supported full CE while undergoing mild apoptosis, whereas mouse oocytectomized COCs (OOXs) cultured in apoptosis-triggering medium underwent severe apoptosis while supporting no CE. RNA- and miRNA-sequencing and bioinformatics using CCs from these cultured COCs/OOXs identified candidate apoptosis- and/or CE-regulating miRNAs. Transfection of COCs/OOXs with miRNA mimic or inhibitor validated that miR-212-5p and 149-5p promoted CE by facilitating Has2 expression; miR-31-5p and 27a-3p promoted CE by increasing both Has2 and Ptx3 expression; and miR-351-5p and 503-5p inhibited CE by suppressing Ptx3 expression. Furthermore, miR-212-5p, 149-5p and Nov798 inhibited CC apoptosis, involving both Bcl2/Bax and Fas signaling. Analysis using in vivo matured COCs further verified the above apoptosis- and/or CE-regulating miRNAs, except for miR-149-5p. In conclusion, this study identified and validated new CE- and apoptosis-regulating miRNAs in CCs, which could be used as biomarkers to select competent oocytes/embryos and for elucidating how the oocyte-derived factors regulate CE and CC apoptosis.

Ethylene glycol butyl ether deteriorates oocyte quality via impairing mitochondrial function.

Ethylene glycol butyl ether (EGBE) is a ubiquitous environmental pollutant that is commonly used in maquillage, industrial, and household products. EGBE has been shown to cause blood toxicity, carcinogenicity, and organ malformations. However, little is known about the impact of EGBE on the female reproductive system, especially oocyte quality. Here, we reported that EGBE influenced oocyte quality by showing the disturbed oocyte meiotic capacity, fertilization potential, and early embryonic development competency. Specifically, EGBE exposure impaired spindle/chromosome structure, microtubule stability, and actin polymerization to result in the oocyte maturation arrest and aneuploidy. In addition, EGBE exposure compromised the dynamics of cortical granules and their component ovastacin, leading to the failure of sperm binding and fertilization. Last, single-cell transcriptome analysis revealed that EGBE-induced oocyte deterioration was caused by mitochondrial dysfunction, which led to the accumulation of ROS and occurrence of apoptosis. Altogether, our study illustrates that mitochondrial dysfunction and redox perturbation is the major cause of the poor quality of oocytes exposed to EGBE.

Wetting States and Departure Diameters of Bubbles on Micro-/Nanostructured Surfaces.

Wetting states for droplets have been extensively investigated in the past. As the counter phase of the droplets, bubbles' wetting states have rarely been systematically explored. The wetting state of a bubble is closely related to its departure diameter, which plays significant roles in bubble-generated processes in boiling heat transfer and gas-evolving reactions. Based on the principle of minimum surface energy, we explicitly define three equilibrium wetting states (hemi-wicking state, Wenzel state, and Cassie-Baxter state) for bubbles on micro-/nanostructured surfaces in this paper. We analyze the three-phase contact line profiles for bubbles under these wetting states and propose theoretical models for predicting departure diameters of hemi-wicking-state bubble and Wenzel-state bubble on micro-/nanostructured surfaces. We identify competing effects of bubble departure in Wenzel state: the augmentation of contact line length due to the roughness, which would delay bubble departure, and the decrease of contact line length due to the reduced apparent contact angle, which would facilitate bubble departure. We demonstrate that hemi-wicking-state bubble exhibits a much smaller departure diameter on the textured surfaces. These findings are supported by numerical simulations by the three-dimensional (3D) multiple-relaxation-time lattice Boltzmann method. It is found that the length of the outermost contact lines instead of all contact lines determines the departure diameter of hemi-wicking-state bubble based on bubble detachment processes captured by our 3D numerical simulations. This work offers an avenue for the accurate prediction and control of bubble departure behaviors from micro-/nanostructured surfaces, and therefore can guide optimal designs of micro-/nanostructured surfaces in a variety of applications in boiling, desalination, and hydrogen production by electrolysis.

How Coalescing Bubbles Depart from a Wall.

Bubble evolution plays a fundamental role in boiling and gas-evolving electrochemical systems. One key stage is bubble departure, which is traditionally considered to be buoyancy-driven. However, conventional understanding cannot provide the full physical picture, especially for departure events with small bubble sizes commonly observed in water splitting and high heat flux boiling experiments. Here, we report a new regime of bubble departure owing to the coalescence of two bubbles, where the departure diameter can be much smaller than the conventional buoyancy limit. We show the significant reduction of the bubble base area due to the dynamics of the three-phase contact line during coalescence, which promotes bubble departure. More importantly, combining buoyancy-driven and coalescence-induced bubble departure modes, we demonstrate a unified relationship between the departure diameter and nucleation site density. By elucidating how coalescing bubbles depart from a wall, our work provides design guidelines for energy systems which can largely benefit from efficient bubble departure.

Coalescence-Induced Bubble Departure: Effects of Dynamic Contact Angles.

Coalescence-induced bubble departure is a common phenomenon in boiling and gas evolution reactions, which has significant impacts on the heat/mass transport. In this work, we systematically investigate the effects of dynamic contact angles on the coalescence and departure processes of two equal-sized bubbles. A critical contact angle (θcr) of 76° is determined for an ideal surface on the basis of a surface energy analysis, beyond which the coalesced bubble does not depart from the wall. Using 3D multi-relaxation-time (MRT) lattice Boltzmann simulations, we demonstrate that the advancing contact angle mainly governs the movement of the outer side of the contact lines, and the increase of the advancing contact angle may delay or even prevent the departure of the coalesced bubble. On the other hand, the receding contact angle dominates the motion of the inner side of the contact lines, and the decrease of the receding contact angle facilitates the departure of the coalesced bubble. We identify a regime map for the coalescence-induced bubble departure with respect to the contact angles, which includes four regions: the all-departure region, the advancing contact angle dominated region, the receding contact angle dominated region, and the nondeparture region. Numerically simulated critical contact angles that separate the above-mentioned regions agree well with theoretical analyses. The results of this study will contribute to the manipulation of bubble behaviors and the optimal design of working surfaces in a variety of energy systems involving boiling and gas-evolving reaction processes.

Rational design of a facile camphor-based fluorescence turn-on probe for real-time tracking of hypochlorous acid in vivo and in vitro.

A simple yet highly effective camphor-derived fluorescent probe named 3-(anthracen-9-ylmethylene)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one oxime (ATHO) was developed based on an oxime recognition receptor and anthracene fluorophore. The probe ATHO exhibited a remarkably enhanced fluorescence response to HClO (∼7.2 fold). Meanwhile, this probe exhibited a low detection limit (0.118 µM), ultrafast response time (within seconds), excellent photostability (>260 min), wide linear range (0-180 µM), low probe concentration (2 µM), and high selectivity toward HClO over various interfering species. The sensing mechanism of the probe ATHO for HClO was supported by HRMS analysis and theoretical calculations. Furthermore, the probe ATHO was utilized to quantitatively determine HClO levels in environmental water samples. Additionally, the biological imaging of the probe ATHO for exogenous and endogenous HClO was successfully demonstrated in vitro and in vivo.

Effect of total laparoscopic versus open pancreaticoduodenectomy on short-term and oncological outcomes: a single-institution comparative study.

BACKGROUND: Recently, the efficacy and outcomes of total laparoscopic pancreaticoduodenectomy (TLPD) have been well established; however, specific data regarding the clinical outcomes of total laparoscopic versus open pancreaticoduodenectomy (OPD) are still limited. The present study aims to directly compare the clinical and oncological outcomes following TLPD versus OPD at a single institution. METHODS: The clinical data of 127 consecutive patients who underwent TLPD (n = 69) and OPD (n = 58) and were admitted to our department between January 2017 and June 2019 were analysed retrospectively. The short-term and oncological outcomes in the two groups were compared. RESULTS: Compared to the OPD group, the TLPD group experienced a longer operative time [(399.1 ± 77.9) min vs. (247.9 ± 61.8) min] and significantly earlier oral intake [5.0 (IQR, 4.0-6.0) days vs. 8.0 (IQR, 6.0-8.0) days], earlier postoperative exhaust [3.0 (IQR, 3.0-4.0) days vs. 4.0 (IQR, 4.0-4.5) days], earlier out-of-bed activity [2.0 (IQR, 1.0-2.3) days vs. 3.0 (IQR, 2.0-3.0) days], earlier nasogastric tube removal [5.5 (IQR, 4.0-7.8) days vs. 8.0 (IQR, 6.0-11.0) days] and shorter postoperative length of hospital stay [14.0 (IQR, 11.0-21.0) days vs. 16.0 (IQR, 12.0-25.0) days] (P < 0.05). The estimated blood loss [(334.4 ± 157.8) mL vs. (344.6 ± 259.1) mL], presence of clinically relevant postoperative pancreatic fistula (grade B/C, 5.8% vs. 5.2%) and the overall complication rate (23.2% vs. 25.9%) did not significantly differ between the two groups (P > 0.05). Regarding the oncological outcomes, there were no significant differences in pathological types, tumour size, lymph nodes harvested, tumour stages or resection margins, or in overall survival (OS) (56.9% vs. 53.2%, P = 0.704) or progression-free survival (PFS) (48.3% vs. 46.8%, P = 0.881) with a median 26-month follow-up. CONCLUSION: TLPD is a safe and feasible procedure in select patients after a certain learning curve. Compared with OPD, TLPD has equivalent short-term and oncological outcomes and offers the advantages of faster postoperative recovery and shorter length of hospital stay.

Heterotopic 4T1 breast cancer transplantation induces hippocampal inflammation and depressive-like behaviors in mice.

Cancer and its accompanying treatments can lead to numerous physical and emotional concerns, including subclinical or clinical depression and anxiety, which could significantly impact one's well-being, quality of life, and survival. A large number of studies have elucidated that neuroinflammation is associated with depression. Here, we report the hippocampal pathological changes and depressive behaviors of a heterotopic breast cancer transplantation mouse model; hence, a heterotopic 4T1 breast cancer transplantation mouse model was established. Assessment of cognitive and locomotive functions of the experimental animals was conducted using open- and closed-field tests, including a tail suspension test. Expression levels of monoaminergic system markers, brain-derived neurotrophic factor (BDNF), pro-inflammatory cytokines, and nuclear factor-kappa B (NFκB) in the hippocampus and serum were detected using immunochemistry and western and enzyme-linked immunosorbent assay analysis. A comparison of the differences between model and control animals was performed. As per our findings, 4T1 tumor-bearing mice displayed cancer-related anorexia/cachexia with significant reductions in the travel distance and the total number of squares crossed in the open- and closed-field tests. Additionally, the 4T1 tumor-bearing mice withstood a more extended period of immobility during the tail suspension test. Immunohistochemistry studies revealed reduced levels of serotonin, norepinephrine, and BDNF in the hippocampus and serum. Elevated levels of NFκB and pro-inflammatory cytokines in the hippocampus were also observed. These findings suggest that hippocampal inflammation may have played an important role in the neurological function and depressive behavior in heterotopic 4T1 breast cancer transplantation mice.

Change in intestinal flora after treatment in children with focal epilepsy. / å±€ç¶æ€§ç™«ç—«æ‚£å„¿æ²»ç–—å‰åŽè‚ é“èŒç¾¤çš„å˜åŒ–åŠæ„ä¹‰.

OBJECTIVES: To study the difference in intestinal flora between children with focal epilepsy and healthy children and the change in intestinal flora after treatment in children with epilepsy. METHODS: A total of 10 children with newly diagnosed focal epilepsy were recruited as the case group and were all treated with oxcarbazepine alone. Their clinical data were recorded. Fecal specimens before treatment and after 3 months of treatment were collected. Fourteen aged-matched healthy children were recruited as the control group. Total bacterial DNA was extracted from the fecal specimens for 16S rDNA sequencing and bioinformatics analysis. RESULTS: After 3 months of carbamazepine treatment, the seizure frequency was reduced by >50% in the case group. At the phylum level, the abundance of Actinobacteria in the case group before treatment was significantly higher than that in the control group (P<0.05), and it was reduced after treatment (P<0.05). At the genus level, the abundances of Escherichia/Shigella, Streptococcus, Collinsella, and Megamonas in the case group before treatment were significantly higher than those in the control group (P<0.05), and the abundances of these bacteria decreased significantly after treatment (P<0.05). CONCLUSIONS: There is a significant difference in intestinal flora between children with focal epilepsy and healthy children. Oxcarbazepine can significantly improve the symptoms and intestinal flora in children with epilepsy.