Shifts in Rumen Fermentation and Microbiota Are Associated with Dissolved Ruminal Hydrogen Concentrations in Lactating Dairy Cows Fed Different Types of Carbohydrates.

BACKGROUND: Different carbohydrates ingested greatly influence rumen fermentation and microbiota and gaseous methane emissions. Dissolved hydrogen concentration is related to rumen fermentation and methane production. OBJECTIVES: We tested the hypothesis that carbohydrates ingested greatly alter the rumen environment in dairy cows, and that dissolved hydrogen concentration is associated with these changes in rumen fermentation and microbiota. METHODS: Twenty-eight lactating Chinese Holstein dairy cows [aged 4-5 y, body weight 480 ± 37 kg (mean ± SD)] were used in a randomized complete block design to investigate effects of 4 diets differing in forage content (45% compared with 35%) and source (rice straw compared with a mixture of rice straw and corn silage) on feed intake, rumen fermentation, and microbial populations. RESULTS: Feed intake (10.7-12.6 kg/d) and fiber degradation (0.584-0.692) greatly differed (P ≤ 0.05) between cows fed the 4 diets, leading to large differences (P ≤ 0.05) in gaseous methane yield (27.2-37.3 g/kg organic matter digested), dissolved hydrogen (0.258-1.64 µmol/L), rumen fermentation products, and microbiota. Ruminal dissolved hydrogen was negatively correlated (r < -0.40; P < 0.05) with molar proportion of acetate, numbers of fungi, abundance of Fibrobacter succinogenes, and methane yield, but positively correlated (r > 0.40; P < 0.05) with molar proportions of propionate and n-butyrate, numbers of methanogens, and abundance of Selenomonas ruminantium and Prevotella spp. Ruminal dissolved hydrogen was positively correlated (r = 0.93; P < 0.001) with Gibbs free energy changes of reactions producing greater acetate and hydrogen, but not correlated with those reactions producing more propionate without hydrogen. CONCLUSIONS: Changes in fermentation pathways from acetate toward propionate production and in microbiota from fibrolytic toward amylolytic species were closely associated with ruminal dissolved hydrogen in lactating dairy cows. An unresolved paradox was that greater dissolved hydrogen was associated with greater numbers of methanogens but with lower gaseous methane emissions.

L-kynurenine induces NK cell loss in gastric cancer microenvironment via promoting ferroptosis.

BACKGROUND: Natural killer (NK) cells play a major role in body's fighting against various types of cancers. Their infiltration in the tumor microenvironment (TME) of gastric cancer (GC) are significantly decreased, which has been reported as a robust prognostic marker. However, the causes leading to NK cells loss in GC TME remains poorly understood. METHODS: We constructed a non-contact co-culturing system and humanized xenograft tumor mice model to detect the influence of GC microenvironment on NK-92 or primary human NK cells viability by flow cytometry. Then through using the specific inhibitors for different types of cell death and examining the surrogate markers, we confirmed ferroptosis in NK cells. Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells. RESULTS: We found L-KYN, mainly generated through indoleamine 2, 3-dioxygenase (IDO) from GC cells, impaired NK cells viability in TME. Further analysis revealed L-KYN induced ferroptosis in NK cells via an AHR-independent way. Moreover, we found NK cells with higher GPX4 expression showed resistance to L-KYN induced ferroptosis. Based on this, we generated GPX4 over-expressed NK-92 cells, and found these cells showed therapeutic potential towards GC. CONCLUSIONS: Our study revealed a novel mechanism to explain the decline of NK cell number in GC TME. Notably, we also developed a potential immunotherapy strategy, which might be beneficial in clinical treatment in the future.

Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer.

BACKGROUND: The current prognostic significance of perigastric tumor deposits (TDs) in gastric cancer (GC) remains unclear. AIM: To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC. METHODS: This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1, 2012 to December 31, 2017 at the Chinese PLA General Hospital. According to the presence of perigastric TDs or not, the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching. The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling. The Kaplan-Meier method was used to plot survival curves. Multivariate Cox regression modeling and the log-rank test were used to analyze the data. RESULTS: Perigastric TDs were found to be positive in 339 (5.09%) of the 6672 patients with GC, among whom 237 were men (69.91%) and 102 were women (30.09%) (2.32:1). The median age was 59 years (range, 27 to 78 years). Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients (P < 0.05). The 1-, 3-, and 5-year overall survival rates of GC patients with TDs were 68.3%, 19.6%, and 11.2%, respectively, and these were significantly poorer than those without TDs of the same stages. There was significant variation in survival according to TD locations among the GC patients (P < 0.05). A new TNM staging framework for GC was formulated according to TD location. When TDs appear in the gastric body, the original stages T1, T2, and T3 are classified as T4a with the new framework, and the original stages T4a and T4b both are classified as T4b. When TDs appear in the lesser curvature, the previous stages N0, N1, N2, and N3 now both are classified as N3. When TDs appear in the greater curvature or the distant tissue, the patient should be categorized as having M1. With the new GC staging scheme including TDs, the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs. CONCLUSION: TDs are a poor prognostic factor for patients with primary GC. The location of TDs is associated with the prognosis of patients with primary GC. Accordingly, we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.

Evaluation of Shear Capacity of Steel Fiber Reinforced Concrete Beams without Stirrups Using Artificial Intelligence Models.

The shear transfer mechanism of steel fiber reinforced concrete (SFRC) beams without stirrups is still not well understood. This is demonstrated herein by examining the accuracy of typical empirical formulas for 488 SFRC beam test records compiled from the literature. To steer clear of these cognitive limitations, this study turned to artificial intelligence (AI) models. A gray relational analysis (GRA) was first conducted to evaluate the importance of different parameters for the problem at hand. The outcomes indicate that the shear capacity depends heavily on the material properties of concrete, the amount of longitudinal reinforcement, the attributes of steel fibers, and the geometrical and loading characteristics of SFRC beams. After this, AI models, including back-propagation artificial neural network, random forest and multi-gene genetic programming, were developed to capture the shear strength of SFRC beams without stirrups. The findings unequivocally show that the AI models predict the shear strength more accurately than do the empirical formulas. A parametric analysis was performed using the established AI model to investigate the effects of the main influential factors (determined by GRA) on the shear capacity. Overall, this paper provides an accurate, instantaneous and meaningful approach for evaluating the shear capacity of SFRC beams containing no stirrups.

LASTR is a novel prognostic biomarker and predicts response to cancer immunotherapy in gastric cancer.

Gastric cancer (GC), a malignant tumor of digestive tract, is characterized by a high death rate. Thus, it is of particular importance to clarify the mechanisms of GC and gain new molecular targets for the sake of preventing and treating GC. It was reported that long non-coding RNAs (IncRNAs) are prognostic factors to cancer. Ferroptosis refers to a process of programmed cell death dependent on iron. This study sets out to investigate the expression and function of ferroptosis-related lncRNA (FRlncRNA) in GC. TCGA datasets offered RNA-seq data for 375 GC patients and clinical data for 443 GC patients. Based on Pearson's correlation analysis, we studied their expression and identified the FRlncRNAs. Differentially expressed prognosis related to FRlncRNA were determined with the help of the Wilcoxon test and univariate Cox regression analysis. To evaluate the accuracy of the prognostic capacity, researchers used the Kaplan-Meier technique, as well as univariate and multivariate Cox regression and receiver operating characteristic (ROC) curve studies. We also carried out the real-time PCR and CCK8 assays to examine the expression and function of FRlncRNA. In this study, we identified 50 ferroptosis-related DEGs which were involved in tumor progression. In addition, we identified 33 survival-related FRlncRNAs. Among them, lncRNA associated with SART3 regulation of splicing(LASTR) was confirmed to be highly expressed in GC specimens compared to non-tumor specimens in this cohort. Survival assays illuminated that the high LASTR expression predicted a shorter overall survival and progression-free survival of GC patients. Based on multivariate Cox regression analyses, it was confirmed that the GC had a worse chance of surviving the disease overall if their tumors expressed LASTR, which was an independent prognostic indication. Then, Loss-of-function tests showed that knocking down LASTR had a significant effect on reducing the proliferation of GC cells. Finally, we found that the expression of LASTR was negatively associated with CD8 T cells, T cells, Th17 cells, and T helper cells. Overall, our findings identified a novel survival-related FRlncRNA, LASTR which possibly can serve as a novel prognostic biomarker predicting response to cancer immunotherapy and therapeutic target for GC patients.

3D laparoscopic-assisted vs open gastrectomy for carcinoma in the remnant stomach: A retrospective cohort study.

BACKGROUND: Three-dimensional (3D) laparoscopic technique has gradually been applied to the treatment of carcinoma in the remnant stomach (CRS), but its clinical efficacy remains controversial. AIM: To compare the short-term and long-term results of 3D laparoscopic-assisted gastrectomy (3DLAG) with open gastrectomy (OG) for CRS. METHODS: The clinical data of patients diagnosed with CRS and admitted to the First Medical Center of Chinese PLA General Hospital from January 2016 to January 2021 were retrospectively collected. A total of 84 patients who met the inclusion and exclusion criteria were enrolled. All their clinical data were collected and a database was established. All patients were treated with 3DLAG or OG by experienced surgeons and were divided into two groups based on the different surgical methods mentioned above. By using outpatient and telephone follow-up, we were able to determine postoperative survival and tumor status. The postoperative short-term efficacy and 1-year and 3-year overall survival (OS) rates were compared between the two groups. RESULTS: Among 84 patients with CRS, 48 were treated with OG and 36 with 3DLAG. All patients successfully completed surgery. There was no significant difference between the two groups in terms of age, gender, body mass index, ASA score, initial disease state (benign or malignant), primary surgical anastomosis method, interval time of carcinogenesis, and tumorigenesis site. Patients in the 3DLAG group experienced less intraoperative blood loss (188.33 ± 191.35 mL vs 305.83 ± 303.66 mL; P = 0.045) and smaller incision (10.86 ± 3.18 cm vs 20.06 ± 5.17 cm; P < 0.001) than those in the OG group. 3DLAGC was a more minimally invasive method. 3DLAGC retrieved significantly more lymph nodes than OG (14.0 ± 7.17 vs 10.73 ± 6.82; P = 0.036), whereas the number of positive lymph nodes did not differ between the two groups (1.56 ± 2.84 vs 2.35 ± 5.28; P = 0.413). The complication rate (8.3% vs 20.8%; P = 0.207) and intensive care unit admission rate (5.6% vs 14.5%; P = 0.372) were equivalent between the two groups. In terms of postoperative recovery, the 3DLAGC group had a lower visual analog score, shorter indwelling time of gastric and drainage tubes, shorter time of early off-bed motivation, shorter time of postoperative initial flatus and initial soft diet intake, shorter postoperative hospital stay and total hospital stay, and there were significant differences, showing better short-term efficacy. The 1-year and 3-year OS rates of OG group were 83.2% [95% confidence interval (CI): 72.4%-95.6%] and 73.3% (95%CI: 60.0%-89.5%) respectively. The 1-year and 3-year OS rates of the 3DLAG group were 87.3% (95%CI: 76.4%-99.8%) and 75.6% (95%CI: 59.0%-97.0%), respectively. However, the 1-year and 3-year OS rates were similar between the two groups, which suggested that long-term survival results were comparable between the two groups (P = 0.68). CONCLUSION: Compared with OG, 3DLAG for CRS achieved better short-term efficacy and equivalent oncological results without increasing clinical complications. 3DLAG for CRS can be promoted safely and effectively in selected patients.

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A mono-institutional propensity score-matched study in China.

BACKGROUND: The potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored. AIM: To compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone. METHODS: A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics. RESULTS: The NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min vs 225.74 ± 45.33 min, P = 0.019) and increased intraoperative blood loss [150 (100-300) mL vs 100 (100-200) mL, P = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, P = 0.024), while NC was not an independent risk factor for postoperative complications in LTG. CONCLUSION: Despite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.

Emergency surgical workflow and experience of suspected cases of COVID-19: A case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 has been confirmed to be a newly discovered zoonotic pathogen that causes highly contagious viral pneumonia, which the World Health Organization has named novel coronavirus pneumonia. Since its outbreak, it has become a global pandemic. During the outbreak of coronavirus disease 2019 (COVID-19), however, there is no mature experience or guidance on how to carry out emergency surgery for suspected cases requiring emergency surgical intervention and perioperative safety protection against virus. CASE SUMMARY: A 41-year-old man was admitted to the hospital for emergency treatment due to "3-d abdominal pain aggravated with cessation of exhaust and defecation". After improving inspections and laboratory tests, the patient was assessed and diagnosed by the multiple discipline team as "strangulation obstruction, pulmonary infection". His body temperature was 38.8 °C, and the chest computed tomography showed pulmonary infection. Given fever and pneumonia, we could not rule out COVID-19 after consultation by fever clinicians and respiratory experts. Hence, we performed emergency surgery under three-level protection for the suspected case. After surgery, his nucleic acid test for COVID-19 was negative, meaning COVID-19 was excluded, and routine postoperative treatment and nursing was followed. The patient was treated with symptomatic support after the operation. The stomach tube and urinary tube were removed on the 1st d after the operation. The clearing diet was started on the 3rd d after the operation, and the body temperature returned to normal. Flatus and bowel movements were noted on 5th postoperative day. He was discharged after 8 d of hospitalization. The patient was followed up for 4 mo after discharge, no serious complications occurred. A 71-year-old woman was admitted to our emergency room due to "abdominal distention, fatigue for 6 d and fever for 13 h". After the multiple discipline team evaluation, the patient was diagnosed as "intestinal obstruction, abdominal mass, peritonitis and pulmonary infection". At that time, the patient's body temperature was 39.6 °C, and chest computed tomography indicated pulmonary infection. COVID-19 could not be completely excluded after consultation in the fever outpatient department and respiratory department. Therefore, the patient was treated as a suspected case, and an urgent operation was performed under three-level medical protection. Postoperative nucleic acid test was negative, COVID-19 was excluded, and routine postoperative treatment and nursing were followed. After the operation, the patient received symptomatic and supportive treatment. The gastric tube was removed on the 1st d after the operation, and the urinary tube was removed on the 3rd d after the operation. Enteral nutrition began on the 3rd d after the operation. To date, no serious complications have been found during follow-up after discharge. CONCLUSION: Based on the previous treatment experience, we reviewed the procedures of two cases of suspected COVID-19 emergency surgery and extracted the perioperative protection experience. By referring to the literature and following the regulations on prevention and management of infectious diseases, we have developed a relatively mature and complete emergency surgical workflow for suspected COVID-19 cases and shared perioperative protection and management experience and measures.

Role of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND: Gastric cancer is the second most common malignant tumor in China, ranking third among all malignant tumor mortality rates. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase significantly the effectiveness of intraperitoneal chemotherapeutic drugs, prolong the action time of these drugs on intraperitoneal tumor cells, and enhance their diffusion in tumor tissues. HIPEC may be one of the best choices for the eradication of residual cancer cells in the abdominal cavity. AIM: The aim of this study was to study the role of preventive HIPEC after radical gastrectomy. METHODS: A prospective analysis was performed with patients with cT4N0-3M0 gastric cancer to compare the effects of postoperative prophylactic HIPEC plus intravenous chemotherapy with those of routine adjuvant chemotherapy. Patients' medical records were analyzed, and differences in the peritoneal recurrence rate, disease-free survival time, and total survival time between groups were examined. RESULTS: The first site of tumor recurrence was the peritoneum in 11 cases in the conventional adjuvant chemotherapy group and in 2 cases in the HIPEC group (P = 0.020). The 1-year and 3-year disease-free survival rates were 91.9% and 60.4%, respectively, in the conventional adjuvant chemotherapy group and 92.1% and 63.0%, respectively, in the HIPEC group. The 1-year and 3-year overall survival rates were 95.2% and 66.3%, respectively, in the conventional adjuvant chemotherapy group and 96.1% and 68.6%, respectively, in the HIPEC group. No significant difference in postoperative or chemotherapy complications was observed between groups. CONCLUSION: In patients with cT4N0-3M0 gastric cancer, prophylactic HIPEC after radical tumor surgery is beneficial to reduce peritoneal tumor recurrence and prolong survival.

Effects of early oral feeding after radical total gastrectomy in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a heavy burden in China. Nutritional support for GC patients is closely related to postoperative rehabilitation. However, the role of early oral feeding after laparoscopic radical total gastrectomy in GC patients is unclear and high-quality research evidence is scarce. AIM: To prospectively explore the safety, feasibility and short-term clinical outcomes of early oral feeding after laparoscopic radical total gastrectomy for GC patients. METHODS: This study was a prospective cohort study conducted between January 2018 and December 2019 based in a high-volume tertiary hospital in China. A total of 206 patients who underwent laparoscopic radical total gastrectomy for GC were enrolled. Of which, 105 patients were given early oral feeding (EOF group) after surgery, and the other 101 patients were given the traditional feeding strategy (control group) after surgery. Perioperative clinical data were recorded and analyzed. The primary endpoints were gastrointestinal function recovery time and postoperative complications, and the secondary endpoints were postoperative nutritional status, length of hospital stay and expenses, etc. RESULTS: Compared with the control group, patients in the EOF group had a significantly shorter postoperative first exhaust time (2.48 ± 1.17 d vs 3.37 ± 1.42 d, P = 0.001) and first defecation time (3.83 ± 2.41 d vs 5.32 ± 2.70 d, P = 0. 004). In addition, the EOF group had a significant shorter postoperative hospitalization duration (5.85 ± 1.53 d vs 7.71 ± 1.56 d, P < 0.001) and lower postoperative hospitalization expenses (16.60 ± 5.10 K¥ vs 21.00 ± 7.50 K¥, P = 0.014). On the 5th day after surgery, serum prealbumin level (214.52 ± 22.47 mg/L vs 204.17 ± 20.62 mg/L, P = 0.018), serum gastrin level (246.30 ± 57.10 ng/L vs 223.60 ± 55.70 ng/L, P = 0.001) and serum motilin level (424.60 ± 68.30 ng/L vs 409.30 ± 61.70 ng/L, P = 0.002) were higher in the EOF group. However, there was no significant difference in the incidence of total postoperative complications between the two groups (P = 0.507). CONCLUSION: Early oral feeding after laparoscopic radical total gastrectomy can promote the recovery of gastrointestinal function, improve postoperative nutritional status, reduce length of hospital stay and expenses while not increasing the incidence of related complications, which indicates its safety, feasibility and potential benefits for gastric cancer patients.