Safety and efficacy of minimally invasive gastrectomy for older patients with gastric cancer after neoadjuvant chemotherapy and immunotherapy: a propensity score-matched analysis.

BACKGROUND: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). METHODS: The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. RESULTS: The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. CONCLUSION: The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827).

MT1M regulates gastric cancer progression and stemness by modulating the Hedgehog pathway protein GLI1.

Gastric cancer (GC) is a highly prevalent and aggressive malignancy with a poor prognosis. Recent evidence suggested that metallothionein 1 M (MT1M) may play a critical role in cancer development, progression, and drug resistance; however, its role in GC remains largely unknown. In this study, we investigated the expression and function of MT1M in GC both in vitro and in vivo. We found that MT1M expression was significantly downregulated in GC tissues and cell lines. Decreased expression of MT1M was associated with worse clinical prognosis, particularly in patients treated with 5-fluorouracil. Low expression of MT1M was indicative of poor overall survival (OS, HR 0.56 [95% CI 0.37-0.84], P < 0.005), first progression survival (FP, HR 0.54 [95% CI 0.36-0.79], P < 0.005), and post-progression survival (PPS, HR 0.65 [95% CI 0.45-0.94], P < 0.05). We also demonstrated that overexpression of MT1M inhibited cell proliferation and induced apoptosis in GC cells and in tumor xenografts, and it improved chemosensitivity to 5-fluorouracil. Furthermore, we found that MT1M overexpression could inhibit stem cell characteristics by targeting GLI1 and affecting GLI1 ubiquitination. Collectively, these findings indicated that MT1M may act as a tumor suppressor in GC and could serve as a potential therapeutic target to attenuate stemness and chemotherapy resistance of GC.

Five-year long-term comparison of robotic and laparoscopic gastrectomy for gastric cancer: a large single-center cohort study.

BACKGROUND: Robotic gastrectomy (RG) has been reported to be technically feasible and safe for patients with gastric cancer. However, 5-year long-term survival and recurrence outcomes for advanced gastric cancer have rarely been reported. This study aimed to compare the long-term oncologic outcomes between RG and laparoscopic gastrectomy (LG) for gastric cancer. METHODS: The general clinicopathological data of 1905 consecutive patients who underwent RG and LG were retrospectively collected at the Chinese People's Liberation Army General Hospital between November 2011 and October 2017. Propensity score matching (PSM) was used to match groups. The primary endpoints were 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: After PSM, a well-balanced cohort of 283 patients in the RG group and 701 patients in the LG group were included in the analysis. The 5-year cumulative DFS rates were 67.28% in the robotic group and 70.41% in the laparoscopic group. The 5-year OS rate was 69.01% in the robotic group and 69.58% in the laparoscopic group. No significant differences in Kaplan-Meier survival curves for DFS (HR = 1.08, 95% CI 0.83-1.39, Log-rank P = 0.557) and OS (HR = 1.02, 95% CI 0.78-1.34, Log-rank P = 0.850) were observed between the 2 groups. In the subgroup analyses for potential confounding variables, there were no significant differences in 5-year DFS and 5-year OS survival between the 2 groups (P > 0.05), except for patients with pathological stage III and pathological stage N3 (P < 0.05). CONCLUSION: For patients with early gastric cancer, robotic and laparoscopic approaches have similar long-term survival. For patients with advanced gastric cancer, further studies need to be conducted to assess the long-term survival outcomes of RG.

Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.

Gastric cancer is a one of the most common malignant tumors with poor prognosis worldwide. Leucine-rich G-protein-coupled receptor 5 (LGR5) is determined as a modulator of Wnt signaling cascade and R-spondins are a family of secretory agonists in the Wnt signaling and act as ligands to interact with LGR5. However, the function of Rspondin-1 in GC remains obscure. Here, we identified the effect of Rspondin-1 on GC progression. Rspondin-1 and LGR5 were upregulated in clinical gastric cancer tissues. CCK-8 assay revealed that the viability of GC cells was reduced by Rspondin-1 depletion and enhanced by Rspondin-1 overexpression. The depletion of Rspondin-1 decreased while the overexpression of Rspondin-1 increased the numbers of colony formation and Edu-positive GC cells. The depletion of Rspondin-1 attenuated the invasion and migration ability of GC cells. Moreover, sphere formation assays revealed that the knockdown of Rspondin-1 reduced the stemness of GC cells. The expression of cancer stem cell markers, including Nanog, OCT3/4, and SOX2 were suppressed by Rspondin-1 depletion in GC cells. Rspondin-1 induced tumor growth of gastric cancer cells in vivo. Mechanically, the cell viability and invasion suppressed by the depletion of Rspondin-1 in GC cells were rescued by LGR5 overexpression. Besides, the overexpression of LGR5 reversed Rspondin-1 knockdown-inhibited Nanog and OCT3/4 expression. Consequently, we concluded that Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.

LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia.

Schizophrenia is a complex genetic disorder, the non-Mendelian features of which are likely complicated by epigenetic factors yet to be elucidated. Here, we performed RNA sequencing of peripheral blood RNA from monozygotic twins discordant for schizophrenia, and identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA, AC006129.1) that participates in the inflammatory response by enhancing SOCS3 and CASP1 expression in schizophrenia patients and further validated this finding in AC006129.1-overexpressing mice showing schizophrenia-related abnormal behaviors. We find that AC006129.1 binds to the promoter region of the transcriptional repressor Capicua (CIC), facilitates the interactions of DNA methyltransferases with the CIC promoter, and promotes DNA methylation-mediated CIC downregulation, thereby ameliorating CIC-induced SOCS3 and CASP1 repression. Derepression of SOCS3 enhances the anti-inflammatory response by inhibiting JAK/STAT-signaling activation. Our findings reveal an epigenetic mechanism with etiological and therapeutic implications for schizophrenia.

Allele-specific DNA methylation maps in monozygotic twins discordant for psychiatric disorders reveal that disease-associated switching at the EIPR1 regulatory loci modulates neural function.

The non-Mendelian features of phenotypic variations within monozygotic twins are likely complicated by environmental modifiers of genetic effects that have yet to be elucidated. Here, we performed methylome and genome analyses of blood DNA from psychiatric disorder-discordant monozygotic twins to study how allele-specific methylation (ASM) mediates phenotypic variations. We identified that thousands of genetic variants with ASM imbalances exhibit phenotypic variation-associated switching at regulatory loci. These ASMs have plausible causal associations with psychiatric disorders through effects on interactions between transcription factors, DNA methylations, and other epigenomic markers and then contribute to dysregulated gene expression, which eventually increases disease susceptibility. Moreover, we also experimentally validated the model that the rs4854158 alternative C allele at an ASM switching regulatory locus of EIPR1 encoding endosome-associated recycling protein-interacting protein 1, is associated with demethylation and higher RNA expression and shows lower TF binding affinities in unaffected controls. An epigenetic ASM switching induces C allele hypermethylation and then recruits repressive Polycomb repressive complex 2 (PRC2), reinforces trimethylation of lysine 27 on histone 3 and inhibits its transcriptional activity, thus leading to downregulation of EIPR1 in schizophrenia. Moreover, disruption of rs4854158 induces gain of EIPR1 function and promotes neural development and vesicle trafficking. Our study provides a powerful framework for identifying regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic variants in mediating psychiatric disorder susceptibility.

Inducing enantioselective crystallization with and self-assembly of star-shaped hybrid polymers prepared via "grafting to" strategy.

Helical polymers present some interesting and distinctive properties, and one of the most distinguished applications of them is the chiral recognition and resolution of enantiomers. In this work, star-shaped hybrid helical poly (phenyl isocyanide) (PPI) with polyhedral oligomeric silsesquioxanes (POSS) as the core was designed and synthesized by "grafting to" strategy. The homoarm star-shaped hybrid POSS-(PPI)8 was first obtained by the click reaction between azide-modified POSS (POSS-(N3 )8 ) and alkynyl-modified PPI (PPI-Alkynyl). The hybrid POSS-(PPI)8 was with predominated left-handed helical conformation and exhibited excellent ability in the enantioselective crystallization of racemic compounds. In the meantime, heteroarm star-shaped hybrid (PEG)4 -POSS-(PPI)4 was prepared by the click reaction of POSS-(N3 )8 with PPI-Alkynyl and alkynyl-modified poly (ethylene glycol) (PEG-Alkynyl). The hybrid (PEG)4 -POSS-(PPI)4 was amphiphilic, and it could self-assemble to form spherical micelles in aqueous solutions.

Prognostic value of lymph node density on cancer staging system for gastric cancer without distal metastasis: a population-based analysis of SEER database.

BACKGROUND: Accurate tumor staging is the cornerstone of tumor treatment. Current tumor staging system for gastric cancer (GC) is based on regional positive lymph nodes while ignoring the total number of examined lymph nodes. We aim to assess the prognostic value of lymph node density (LND), the ratio of positive nodes to the total number examined nodes, in GC without distal metastasis. METHODS: Clinical information of patients with histologically confirmed GC and without distal metastasis was identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-Tile software was used to identify the ideal prognosis-related cutoff point for LND. The prognostic value of LND on cancer-specific survival (CSS) and overall survival (OS) was assessed in Cox regression models. Subgroup analysis stratified by LND was performed on current lymph node staging system to further explore the interaction between LND and current lymph node staging system. RESULTS: A total of 4281 participants were identified from the SEER database for the final analysis. The optimal prognosis-related cutoff values of LND were calculated as 0.1 and 0.4, and LND was divided into three levels: LND1 (< 0.1), LND2 (> = 0.1, < 0.4), and LND3 (> = 0.4). LND3 was associated with worse CSS and OS in GC patients. Compared to patients with LND1, those with LND2 and LND3 had 2.43 (HR = 2.43, 95% CI 2.09-2.84, P < 0.001) and 4.69 (HR = 4.69, 95% CI 4.02-5.48, P < 0.001) folds increase in mortality in CSS, respectively. Similar results were found in the evaluation of OS in GC patients. Subgroup analysis stratified by LND also found that patients in the same current lymph node stage still had different prognosis due to the different LND levels after adjustment for other prognosis-related covariates (all P values < 0.001). CONCLUSION: LND is an independent prognostic factor for GC without distal metastasis. In the current lymph node staging system, LND has potential value in further accurately classifying GC patients without distal metastasis.

Defining the impact of platelet-to-lymphocyte ratio on patient survival with gastric neuroendocrine neoplasm: a retrospective cohort analysis.

BACKGROUND: Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN). METHODS: A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels. RESULTS: In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32-2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28-2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202-1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1-3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05). CONCLUSION: The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.

CXCL2 attenuates osteoblast differentiation by inhibiting the ERK1/2 signaling pathway.

The C-X-C motif chemokine ligand 2 (CXCL2), a member of the CXC receptor ligand family, is involved in various immune and inflammatory processes, but its effect(s) on bone formation have not yet been reported. We report here that CXCL2 is enriched in bone marrow and show abundant expression of CXCL2 in osteoblasts of osteoporotic mice. CXCL2 neutralization within the bone marrow by using antibody alleviated bone loss in mice, indicating a negative role of CXCL2 in bone formation. In line with this, CXCL2 overexpression attenuated proliferation, as well as differentiation, of osteoblasts in vitro By contrast, CXCL2 downregulation promoted osteoblast expansion and differentiation. Mechanistically, CXCL2 inhibits the ERK1/2 (MAPK3/1) signaling pathway in osteoblasts. Activation of ERK1/2 abolishes the inhibitory effect of CXCL2 in osteoblasts, whereas inactivation of ERK1/2 reverses the osteogenic role of CXCL2 inhibition. These results show that CXCL2 attenuates osteoblast differentiation through inhibition of the ERK1/2 signaling pathway. We demonstrate here that CXCL2 is a negative regulator of bone formation and clarify the responsible mechanisms. Therefore, pharmaceutical coordination of CXCL2 and of the pathways through which it is regulated in osteoblasts might be beneficial regarding bone formation.

GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in gastric cancer.

It is vital to identify effective therapeutic targets and explore the underlying mechanisms to curb the progression of Gastric cancer (GC) and improve the prognosis of GC patients. Guanine-rich RNA sequence binding factor 1 (GRSF1) is a member of the RNA-binding protein family. The present study showed that GRSF1 knockdown suppressed GC cells proliferation, migration and invasion in vitro, while GRSF1 overexpression enhanced the proliferation, migration and invasion of GC cells. Meanwhile, knockdown of GRSF1 inhibited tumor growth and tumor metastasis in vivo. Furthermore, we demonstrated that GRSF1 induced epithelial-mesenchymal transition (EMT) and activated PI3K/AKT pathway in vitro and in vivo through gain and loss of function. In conclusion, we demonstrated that GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in GC. Our study for the first time identified the functions of GRSF1 serving as an oncogene in GC, which may be a potential effective therapeutic target and malignant indicator in GC.

MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. METHODS: Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. RESULTS: GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. CONCLUSIONS: MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

Effect of preoperative nutrition therapy type and duration on short-time outcomes in gastric cancer patient with gastric outlet obstruction.

OBJECTIVE: To avoid perioperative complications caused malnutrition, nutrition therapy is necessary in gastric outlet obstruction (GOO) patients. Compared to parenteral nutrition (PN), enteral nutrition (EN) is associated with many advantages. This study aimed to investigate whether preoperative EN has beneficial clinical effects compared to preoperative PN in gastric cancer patients with GOO undergoing surgery. METHODS: According to the methods of preoperative nutrition therapy, 143 patients were divided into EN group (n=42) and PN group (n=101) between January 2013 and December 2017 at the Chinese People's Liberation Army General Hospital. Multiple logistic regression models were used to assess the association between the methods of preoperative nutrition therapy and postoperative day of flatus passage. The generalized additive model and two-piecewise linear regression model were used to calculate the inflection point of the preoperative nutritional therapy time on the postoperative day of flatus passage in the PN group. RESULTS: EN shortened the postoperative day of flatus passage in gastric cancer patients with GOO, which is a protective factor, especially in patients who underwent non-radical operations and the postoperative day of flatus passage reduced when the preoperative PN therapy was up to 3 d and a longer PN therapy (>3 d) did not accelerate the postoperative recovery of gastrointestinal functions. CONCLUSIONS: Preoperative EN therapy would benefit gastric cancer patients with GOO by accelerating postoperative recovery. For patients with absolute obstruction, no more than 3-day PN therapy is recommended if patients can tolerate general anesthesia and surgery.

Stearoyl-CoA-desaturase-1 regulates gastric cancer stem-like properties and promotes tumour metastasis via Hippo/YAP pathway.

BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1) is reported to play essential roles in cancer stemness among several cancers. Our previous research revealed significant overexpression of SCD1 in primary gastric cancer stem cells (GCSCs), with its functional role still unknown. METHODS: We stably established three primary GCSCs by sphere-forming assays and flow cytometry. Protein quantification and bioinformatics analysis were performed to reveal the differential protein pattern. Lentivirus-based small-interfering RNA (siRNA) knockdown and pharmacological inhibition approaches were used to characterise the function and molecular mechanism role of SCD1 in the regulation of GC stemness and tumour metastasis capacity both in vitro and in vivo. RESULTS: SCD1 was found to increase the population of GCSCs, whereas its suppression by an SCD1 inhibitor or knockdown by siRNA attenuated the stemness of GCSCs, including chemotherapy resistance and sphere-forming ability. Furthermore, SCD1 suppression reversed epithelial-to-mesenchymal transition and reduced the GC metastasis probability both in vitro and in vivo. Downregulation of SCD1 in GCSCs was associated with the expression of Yes-associated protein (YAP), a key protein in the Hippo pathway, and nuclear YAP translocation was also blocked by the SCD1 decrease. CONCLUSIONS: SCD1 promotes GCSC stemness through the Hippo/YAP pathway. Targeting SCD1 might be a novel therapeutic strategy, especially to suppress GC metastasis and sensitise chemotherapy.

JS-K induces reactive oxygen species-dependent anti-cancer effects by targeting mitochondria respiratory chain complexes in gastric cancer.

As a nitric oxide (NO) donor prodrug, JS-K inhibits cancer cell proliferation, induces the differentiation of human leukaemia cells, and triggers apoptotic cell death in various cancer models. However, the anti-cancer effect of JS-K in gastric cancer has not been reported. In this study, we found that JS-K inhibited the proliferation of gastric cancer cells in vitro and in vivo and triggered mitochondrial apoptosis. Moreover, JS-K induced a significant accumulation of reactive oxygen species (ROS), and the clearance of ROS by antioxidant reagents reversed JS-K-induced toxicity in gastric cancer cells and subcutaneous xenografts. Although JS-K triggered significant NO release, NO scavenging had no effect on JS-K-induced toxicity in vivo and in vitro. Therefore, ROS, but not NO, mediated the anti-cancer effects of JS-K in gastric cancer. We also explored the potential mechanism of JS-K-induced ROS accumulation and found that JS-K significantly down-regulated the core proteins of mitochondria respiratory chain (MRC) complex I and IV, resulting in the reduction of MRC complex I and IV activity and the subsequent ROS production. Moreover, JS-K inhibited the expression of antioxidant enzymes, including copper-zinc-containing superoxide dismutase (SOD1) and catalase, which contributed to the decrease of antioxidant enzymes activity and the subsequent inhibition of ROS clearance. Therefore, JS-K may target MRC complex I and IV and antioxidant enzymes to exert ROS-dependent anti-cancer function, leading to the potential usage of JS-K in the prevention and treatment of gastric cancer.

Nanoscaled pearl powder accelerates wound repair and regeneration in vitro and in vivo.

Pearl powder has been used to treat many diseases like palpitations, insomnia, and epilepsy for thousands of years in Chinese medicine. It has demonstrated antioxidant, antiaging, antiradiative, and tonic activities. Pearl powder contains multiple active proteins, which are nutritious for skin cells and might be advantageous for wound repair and regeneration. However, its healing effect in vivo was not reported yet. This study aims to investigate the effects and the underlying mechanism of the pearl powders with different particle sizes in wound treatment. Briefly, the pearl powder with different sizes was characterized for their particle sizes and morphology. The protein release profiles of these powders were also studied. The influence of the different size of pearl powder in the proliferation, migration of skin cells was evaluated. Then, with the rat skin excision model, the effect of pearl powder on wound repair and regeneration was investigated. It was demonstrated that, all the micro and nanosized pearl powders could both increase the proliferation and migration of skin cells and accelerate the wound closure, as well as significantly enhanced the biomechanic strength of the healed skins. Moreover, the pearl powder treatment could improve the formation and regular deposition of collagen, and enhance the skin angiogenesis. Among all these in vitro and in vivo investigations, nanoscale pearl powder expressed the highest efficiency for healing. The mechanism might be contributed to the increased release of active proteins, enhanced tissue attachment, and the increased cellular uptake for the nano powder at the topical site.

Robot-Assisted Versus Laparoscopy-Assisted Proximal Gastrectomy for Early Gastric Cancer in the Upper Location: Comparison of Oncological Outcomes, Surgical Stress, and Nutritional Status.

BACKGROUND: An increasing amount of attention has been paid to minimally invasive function-preserving gastrectomy, with an increase in incidence of early gastric cancer in the upper stomach. This study aimed to compare oncological outcomes, surgical stress, and nutritional status between robot-assisted proximal gastrectomy (RAPG) and laparoscopy-assisted proximal gastrectomy (LAPG). METHODS: Eighty-nine patients were enrolled in this retrospective study between November 2011 and December 2013. Among them, 27 patients underwent RAPG and 62 underwent LAPG. Perioperative parameters, surgical stress, nutritional status, disease-free survival, and overall survival were compared between the 2 groups. RESULTS: Sex, age, and comorbidity were similar in the RAPG and LAPG groups. There were also similar perioperative outcomes regarding operation time, complications, and length of hospital stay between the groups. The reflux esophagitis rates following RAPG and LAPG were 18.5% and 14.5%, respectively ( P = .842). However, patients in the RAPG group had less blood loss ( P = .024), more harvested lymph nodes ( P = .021), and higher costs than those in the LAPG group ( P < .001). With regard to surgical stress, no significant differences were observed in C-reactive protein concentrations and white blood cell count on postoperative days 1, 3, and 7 between the groups ( Ps > .05). There appeared to be higher hemoglobin levels at 6 months ( P = .053) and a higher body mass index at 12 months ( P = .056) postoperatively in patients in the RAPG group compared with those in the LAPG group, but this difference was not significant. Similar disease-free survival and overall survival rates were observed between the groups. CONCLUSIONS: RAPG could be an alternative to LAPG for patients with early gastric cancer in the upper stomach with comparable oncological safety and nutritional status. Further well-designed, prospective, large-scale studies are needed to validate these results.

Minimally invasive surgery as a treatment option for gastric cancer with liver metastasis: a comparison with open surgery.

BACKGROUND: As minimally invasive techniques advances, minimally invasive surgery (MIS) has emerged as an alternative modality for advanced gastric cancer. In this study, we compared the short- and long-term surgical outcomes of MIS and conventional open surgery for gastric cancer liver metastasis (GCLM) in terms of safety, feasibility, and efficacy. METHODS: This retrospective study used data from a prospective database at the Chinese People's Liberation Army General Hospital. From January 2006 to June 2016, 53 gastric cancer patients with synchronous liver metastasis accepted radical gastrectomy combined with either or both hepatectomy and radiofrequency ablation for liver metastases. The 53 patients enrolled in the study were divided into two groups: a conventional open surgery group (n = 42) and an MIS group (n = 11). Propensity score matching (PSM) analysis was performed to overcome possible bias. RESULTS: With PSM performed at a 1:3 ratio, 11 patients who received MIS were compared with 33 open surgery cases. Mean operation time was significantly longer for the MIS group compared with the open surgery group (301 vs. 236 min, P = 0.032), while the open surgery group had a larger estimated blood loss than the MIS group (421 vs. 196 ml, P = 0.019). Time to first flatus and postoperative complications, including Clavien-Dindo classification, were similar in the two groups. However, patients undergoing MIS had a significantly shorter time to first sips of water (P = 0.020) and soft diet (P = 0.020) compared with open surgery counterparts. Long-term outcomes were comparable between groups (P = 0.090) after adjustment by PSM analysis. CONCLUSIONS: MIS achieved superior short-term outcomes and comparable long-term outcomes compared with open surgery in GCLM patients. For experienced surgeons, both laparoscopic and robotic methods of MIS are reasonable approaches for the management of highly selected GCLM patients.

Delivery of risperidone from gels across porcine skin in vitro and in vivo in rabbits.

The purpose of this study was to develop and evaluate a transdermal delivery system for RIS using hydrogels. First, the effects of different concentrations of hydroxypropyl methylcellulose and Carbomer 934 (CBR) on RIS permeation were investigated in porcine skin. The optimized formulation was chosen as the base gel to screen for penetration enhancers. The pharmacokinetics of the optimized RIS formulation was then studied in vitro in rabbits. A formulation with 0.5% CBR showed the highest RIS permeation and was selected as the base gel. RIS permeation was further increased by incorporation of Azone, lauryl alcohol, or menthol, and the enhancing effects of the three were dose-dependent. When each enhancer combined with propylene glycol (PG) a synergistic effect was found. A combination of 6% menthol and 6% PG exhibited highest RIS in vitro penetration rate and showed a high efficiency in vivo, with a relative bioavailability of 131.53% compared with intragastric administration. These findings showed that 1% RIS in 0.5% CBR, containing a combination of 6% menthol and 6% PG, can deliver doses of RIS that are therapeutically relevant for treating patients with schizophrenia.

Skin permeation profile and anti-inflammatory effect of anemonin extracted from weilingxian.

The aim of this study was to evaluate the skin permeability of anemonin, which was extracted from the Chinese herb weilingxian, and its potency of relieving the inflammation caused by rheumatoid arthritis (RA). To optimize the formulation, the solubility of anemonin in water and selected concentration of ethanol-water vehicles was determined. The effect of ethanol on the permeation of anemonin through human skin was then studied. Additionally, the influences of hydroxypropyl methylcellulose E50 (HPMC) and Carbomer 934 in different concentrations on the permeation of drug were investigated. Finally, the anti-inflammatory effect of the optimized formulation was assessed by murine model of xylene-induced ear edema. The results showed that the solubility and transdermal permeation of anemonin in ethanol-water vehicles linearly depended on the ethanol concentration. The combination of 30% ethanol and 3% Azone had a synergistic enhancement effect and was therefore selected for gel preparation. The 0.14% anemonin gel prepared with 1% HPMC exhibited the highest transdermal flux. The xylene-induced ear edema inhibitory rate of the optimized formulation was 48.85%. The results indicated that transdermal administration of anemonin is a potential modality for combating inflammation caused by RA.