Laparoscopic Spleen-Preserving Hilar Lymphadenectomy for Advanced Proximal Gastric Cancer Without Greater Curvature Invasion: Five-Year Outcomes From the Fuges-02 Randomized Clinical Trial.

Importance: Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion. Objective: To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC. Design, Setting, and Participants: This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023. Interventions: Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups. Main Outcomes and Measures: The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared. Results: A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01). Conclusions: This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.

Enlightenment of robotic gastrectomy from 527 patients with gastric cancer in the minimally invasive era: 5 years of optimizing surgical performance in a high-volume center - a retrospective cohort study.

BACKGROUND: Learning curves have been used in the field of RG. However, it should be noted that the previous study did not comprehensively investigate all changes related to the learning curve.This study aims to establish a learning curve for radical robotic gastrectomy (RG) and evaluate its effect on the short-term outcomes of patients with gastric cancer. METHODS: The clinicopathological data of 527 patients who underwent RG between August 2016 and June 2021 were retrospectively analyzed. Learning curves related to the operation time and postoperative hospital stay were determined separately using cumulative sum (CUSUM) analysis. Then, the impact of the learning curve on surgical efficacy was analyzed. RESULTS: Combining the CUSUM curve break points and technical optimization time points, the entire cohort was divided into three phases (patients 1-100, 101-250, and 251-527). The postoperative complication rate and postoperative recovery time tended to decrease significantly with phase advancement (P<0.05). More extraperigastric examined lymph nodes (LN) were retrieved in phase III than in phase I (I vs. III, 15.12±6.90 vs. 17.40±7.05, P=0.005). The rate of LN noncompliance decreased with phase advancement. Textbook outcome (TO) analysis showed that the learning phase was an independent factor in TO attainment (P<0.05). CONCLUSION: With learning phase advancement, the short-term outcomes were significantly improved. It is possible that our optimization of surgical procedures could have contributed to this improvement. The findings of this study facilitate the safe dissemination of RG in the minimally invasive era.

Integrative ATAC-seq and RNA-seq analysis of myogenic differentiation of ovine skeletal muscle satellite cell.

Skeletal muscle satellite cells (SMSCs) play an important role in regulating muscle growth and regeneration. Chromatin accessibility allows physical interactions that synergistically regulate gene expression through enhancers, promoters, insulators, and chromatin binding factors. However, the chromatin accessibility altas and its regulatory role in ovine myoblast differentiation is still unclear. Therefore, ATAC-seq and RNA-seq analysis were performed on ovine SMSCs at the proliferation stage (SCG) and differentiation stage (SCD). 17,460 DARs (differential accessibility regions) and 3732 DEGs (differentially expressed genes) were identified. Based on joint analysis of ATAC-seq and RNA-seq, we revealed that PI3K-Akt, TGF-ß and other signaling pathways regulated SMSCs differentiation. We identified two novel candidate genes, FZD5 and MAP2K6, which may affect the proliferation and differentiation of SMSCs. Our data identify potential cis regulatory elements of ovine SMSCs. This study can provide a reference for exploring the mechanisms of the differentiation and regeneration of SMSCs in the future.

Impact of chemotherapy delay on long-term prognosis of laparoscopic radical surgery for locally advanced gastric cancer: a pooled analysis of four randomized controlled trials.

BACKGROUND: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II-III locally AGC and explore the associated risk factors. METHODS: Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established. RESULTS: In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II-III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets. CONCLUSION: Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II-III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.

Electroacupuncture attenuates neuropathic pain via suppressing BIP-IRE-1α-mediated endoplasmic reticulum stress in the anterior cingulate cortex.

Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.

Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4-ß-catenin complex and downregulation of SOX9.

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.

Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer.

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.

Effects of tumor marker regression load score on long-term prognosis of gastric cancer patients undergoing radical surgery after neoadjuvant chemotherapy.

BACKGROUND: The effects of the dynamics of serum tumor markers (CA72-4, CEA, CA19-9, CA125 and AFP) before and after neoadjuvant chemotherapy (NACT) on the prognosis of gastric cancer(GC) patients remain unclear. METHODS: The training set contained 334 GC patients from Fujian Medical University Union Hospital (FJMUUH) and 113 GC patients in Qinghai University Affiliated Hospital (QhUAH) were used as an external validation set. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker- preNACT marker)/preNACT marker]. Tumor marker regression load score (TMRLS) consists of ΔCA72-4, ΔCEA and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic(ROC) curve(AUC), decision curve analysis(DCA), and C-index. RESULTS: Patients from FJMUUH were divided into two groups, TMRLS-low and TMRLS-high, determined by R package maxstat. Survival analysis revealed a higher 3-year overall survival(OS) in the TMRLS-low than in the TMRLS-high group. The TMRLS-high group who received postoperative adjuvant chemotherapy(AC) showed a significantly higher 3-year OS rate than those who did not. Multivariate COX regression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS showed a significantly higher C-index and AUC than the ypTNM stage. The above results were also found in the QhUAH external validation cohort. CONCLUSION: TMRLS is a novel independent prognostic factor for GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, may achieve better survival outcomes. Notably, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage.

Robotic versus laparoscopic distal gastrectomy for resectable gastric cancer: a randomized phase 2 trial.

Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate.

The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicenter Real-world clinical study.

BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analysed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% versus [vs.] 59.0%; P<0.001), pathological complete response rate (14.36% vs. 6.41%; P=0.002) and major pathological response rate (39.49% vs. 26.15%; P=0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P=0.694) and proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P=0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P=0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence (odds ratio 0.62 [95% CI 0.41-0.92]; P=0.018). No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P=0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates, and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.

An improved technology for monitoring groundwater flow velocity and direction in fractured rock system based on colloidal particles motion.

The colloidal borescope, using colloidal particle motion, is used to monitor the flow velocities and directions of groundwater. It integrates advanced techniques such as microscopy, high-speed photography, and big data computing and enjoys high sensitivity at the micron level. However, In the same well, the groundwater flow velocity monitored by colloidal hole mirror is varies greatly from that obtained by conventional hydrogeological monitoring, such as pumping test. In order to solve this problem, the stability catcher and stratified packer are designed to control the interference of the vertical flow in drilling, and to monitor the flow velocity and direction of groundwater velocity at the target aquifer and target fracture. Five wells with different aquifers and different groundwater types were selected for monitoring in south-central China. The instantaneous velocity and direction are converted into east-west component and north-south component, the average velocity and direction is calculated according to the time of 10 min, and the particle trajectory diagram is established. Based on these results, it proposed a concept of cumulative flow velocity. Using curve-fitting equations, the limits of cumulative flow velocities as the monitoring time tends to infinity were then calculated as the actual flow velocities of the groundwater. The permeability coefficient of aquifer is calculated by using the fissure ratio of aquifer, hydraulic slope and flow velocity, and compared with the permeability coefficient obtained by pumping test. The results are as follows: (1) The variation coefficient of the instantaneous flow velocity measured at the same depth in the same well at different times is greater than that of the time average flow velocity and greater than that of the cumulative flow velocity. The variation coefficient of the actual velocity is the smallest, indicating that the risk of using the actual flow velocity is lower. (2) The variation coefficient of the flow rate monitored at different depths in the same well is mainly controlled by the properties of the aquifer. The more uniform water storage space in the aquifer, the smaller the variation coefficient. (3) The comparison between the permeability coefficient obtained by monitoring and the permeability coefficient obtained by pumping test shows that the flow of structural fissure water controlled by planar fissure is more surface flow, and the results are consistent. When the groundwater flow is controlled by pores and solution gaps, the flow channel is complicated, which is easy to produce turbulent flow, and the result consistency is poor. (4) According to different research accuracy requirements, different monitoring and calculation methods can be selected for different aquifers and groundwater types. Researches show that, the permeability coefficient calculated for the actual flow velocity in well DR01 is the same as that calculated for the pumping test. The aquifer characteristics reflected by the coefficient of variation of the actual flow velocity in the same aquifer are more realistic. The pumping test method obtains the comprehensive parameters of a certain aquifer, and this method can be used to monitor a certain fissure. In this paper, the new technology developed for monitoring, and the new algorithm established for data processing, can accurately obtain the flow velocity and direction of groundwater, using capsule hole mirror monitoring method. The key parameters of hydrogeology can be obtained by using one well, which can reduce the time and cost input and improve the work efficiency.

Electrospun Fenoprofen/Polycaprolactone @ Tranexamic Acid/Hydroxyapatite Nanofibers as Orthopedic Hemostasis Dressings.

Dressings with multiple functional performances (such as hemostasis, promoting regeneration, analgesia, and anti-inflammatory effects) are highly desired in orthopedic surgery. Herein, several new kinds of medicated nanofibers loaded with several active ingredients for providing multiple functions were prepared using the modified coaxial electrospinning processes. With an electrospinnable solution composed of polycaprolactone and fenoprofen as the core working fluid, several different types of unspinnable fluids (including pure solvent, nanosuspension containing tranexamic acid and hydroxyapatite, and dilute polymeric solution comprising tranexamic acid, hydroxyapatite, and polyvinylpyrrolidone) were explored to implement the modified coaxial processes for creating the multifunctional nanofibers. Their morphologies and inner structures were assessed through scanning and transmission electron microscopes, which all showed a linear format without the discerned beads or spindles and a diameter smaller than 1.0 µm, and some of them had incomplete core-shell nanostructures, represented by the symbol @. Additionally, strange details about the sheaths' topographies were observed, which included cracks, adhesions, and embedded nanoparticles. XRD and FTIR verified that the drugs tranexamic acid and fenoprofen presented in the nanofibers in an amorphous state, which resulted from the fine compatibility among the involved components. All the prepared samples were demonstrated to have a fine hydrophilic property and exhibited a lower water contact angle smaller than 40° in 300 ms. In vitro dissolution tests indicated that fenoprofen was released in a sustained manner over 6 h through a typical Fickian diffusion mechanism. Hemostatic tests verified that the intentional distribution of tranexamic acid on the shell sections was able to endow a rapid hemostatic effect within 60 s.

Establishing an astaxanthin-rich live feed strain of Pseudodiaptomus annandalei.

This study aimed to establish an astaxanthin-rich strain of the calanoid copepod Pseudodiaptomus annandalei, through selective breeding based on RGB (red, green and blue) value, a parameter indicating color intensity. We evaluated the RGB value frequency distributions of the copepod populations, and selected individuals with the highest 10% and the lowest 10% RGB value over six generations. The RGB value, nauplii production, clutch interval and clutch number were assessed, and the genetic gain was calculated across generations (G0-G5). Two strains of copepods were selected and defined as dark body copepod strain (DBS) and light body copepod strain (LBS) at the end of experiment. Results revealed significantly lower RGB values (male: 121.5 ± 14.1; female: 108.8 ± 15) in the G5 DBS population compared to the G0 (male: 163.9 ± 13.1; female: 162.2 ± 14.6), with higher genetic gains of RGB values during G0 to G2. While DBS females exhibited longer clutch intervals in the G3 and G4, there was no significant difference in nauplii production between the two strains across all generations. Significantly higher astaxanthin content was found in the DBS copepods (0.04 µg/ ind.) compared to the LBS copepods (0.01 µg/ ind.) and the non-selective copepods (0.02 µg/ ind.) 20 months post selective breeding, validating the stability of the desired trait in the DBS strain. This study successfully established an astaxanthin-rich strain of P. annandalei, which provides implications for enhancing marine and brackish larviculture production.

The safety, feasibility and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0% vs. 35.0%, P=0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9% vs. 32.8%, P=0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P=0.173; OS: log-rank P=0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P>0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was non-inferior to OCTG in both short- and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

BACKGROUND: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. METHODS: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (- 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. CONCLUSION: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Genomic Inbreeding and Runs of Homozygosity Analysis of Cashmere Goat.

Cashmere goats are valuable genetic resources which are famous worldwide for their high-quality fiber. Runs of homozygosity (ROHs) have been identified as an efficient tool to assess inbreeding level and identify related genes under selection. However, there is limited research on ROHs in cashmere goats. Therefore, we investigated the ROH pattern, assessed genomic inbreeding levels and examined the candidate genes associated with the cashmere trait using whole-genome resequencing data from 123 goats. Herein, the Inner Mongolia cashmere goat presented the lowest inbreeding coefficient of 0.0263. In total, we identified 57,224 ROHs. Seventy-four ROH islands containing 50 genes were detected. Certain identified genes were related to meat, fiber and milk production (FGF1, PTPRM, RERE, GRID2, RARA); fertility (BIRC6, ECE2, CDH23, PAK1); disease or cold resistance and adaptability (PDCD1LG2, SVIL, PRDM16, RFX4, SH3BP2); and body size and growth (TMEM63C, SYN3, SDC1, STRBP, SMG6). 135 consensus ROHs were identified, and we found candidate genes (FGF5, DVL3, NRAS, KIT) were associated with fiber length or color. These findings enhance our comprehension of inbreeding levels in cashmere goats and the genetic foundations of traits influenced by selective breeding. This research contributes significantly to the future breeding, reservation and use of cashmere goats and other goat breeds.

Long-term survival outcomes of robotic total gastrectomy for locally advanced proximal gastric cancer: a prospective study.

BACKGROUND: Robotic gastrectomy is a safe and feasible approach for gastric cancer (GC); however, its long-term oncological efficacy remains unclear. We evaluated the long-term survival outcomes and recurrence patterns of patients with locally advanced proximal GC who underwent robotic total gastrectomy (RTG). METHODS: This prospective study (FUGES-014 study) enrolled 48 patients with locally advanced proximal GC who underwent RTG between March 2018 and February 2020 at a tertiary referral teaching hospital. Patients who underwent laparoscopic total gastrectomy (LTG) in the FUGES-002 study were enrolled in a 2:1 ratio to compare the survival outcomes between RTG and LTG. The primary endpoint of the FUGES-014 study was postoperative 30-day morbidity and has been previously reported. Here we reported the results of 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence patterns. RESULTS: After propensity score matching, 48 patients in the RTG and 96 patients in the LTG groups were included. The 3-year DFS rates were 77.1% (95% confidence interval [CI] 66.1-89.9%) for the RTG and 68.8% (95% CI 60.1-78.7%) for the LTG groups ( P =0.261). The 3-year OS rates were not significantly different between the groups (85.4% vs. 74.0%, P =0.122). Recurrence occurred in nine patients (18.8%) in the RTG and 27 (28.1%) patients in the LTG groups ( P =0.234). Recurrence patterns and causes of death were similar between the groups ( P >0.05). CONCLUSIONS: The oncological outcome of RTG was non-inferior to that of LTG. Thus, RTG might be an alternative surgical treatment for locally advanced proximal GC.

Runs of Homozygosity Detection and Selection Signature Analysis for Local Goat Breeds in Yunnan, China.

Runs of Homozygosity (ROH) are continuous homozygous DNA segments in diploid genomes, which have been used to estimate the genetic diversity, inbreeding levels, and genes associated with specific traits in livestock. In this study, we analyzed the resequencing data from 10 local goat breeds in Yunnan province of China and five additional goat populations obtained from a public database. The ROH analysis revealed 21,029 ROH segments across the 15 populations, with an average length of 1.27 Mb, a pattern of ROH, and the assessment of the inbreeding coefficient indicating genetic diversity and varying levels of inbreeding. iHS (integrated haplotype score) was used to analyze high-frequency Single-Nucleotide Polymorphisms (SNPs) in ROH regions, specific genes related to economic traits such as coat color and weight variation. These candidate genes include OCA2 (OCA2 melanosomal transmembrane protein) and MLPH (melanophilin) associated with coat color, EPHA6 (EPH receptor A6) involved in litter size, CDKAL1 (CDK5 regulatory subunit associated protein 1 like 1) and POMC (proopiomelanocortin) linked to weight variation and some putative genes associated with high-altitude adaptability and immune. This study uncovers genetic diversity and inbreeding levels within local goat breeds in Yunnan province, China. The identification of specific genes associated with economic traits and adaptability provides actionable insights for utilization and conservation efforts.

PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

Aims: Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods: Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results: The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion: The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.