Pain Sensitivity and Acute Postoperative Pain in Patients Undergoing Abdominal Surgery: The Mediating Roles of Pain Self-Efficacy and Pain Catastrophizing.

BACKGROUND: Inadequately managed postoperative pain remains a common issue. Examining factors like pain sensitivity, pain catastrophizing, and pain self-efficacy can help improve postoperative pain management. While these factors have been identified as potential predictors of acute postoperative pain, their effects have been inconsistent. Few studies have explored the interactions between these factors. AIM: To investigate the influence of preoperative pain sensitivity, pain catastrophizing, and pain self-efficacy on acute postoperative pain in abdominal surgery patients and to determine the mediating roles of pain catastrophizing and pain self-efficacy in the relationship between pain sensitivity and acute postoperative pain, as per the gate control theory. METHODS: A total of 246 patients were enrolled in this study. General information was collected before surgery, and the Pain Sensitivity Questionnaire (PSQ), Pain Catastrophizing Scale (PCS), and Pain Self-Efficacy Questionnaire (PSEQ) were administered. After surgery, patients' average pain scores over the 24 hours were reported using the Numerical Rating Scale (NRS). Correlation analyses and a structural equation model were used to examine the relationships among these variables. RESULTS: NRS scores over 3 during the 24 hours post-surgery were reported by 21.54% of patients. Postoperative acute pain was found to be associated with pain sensitivity (rs = 0.463, p < .001), pain catastrophizing (rs = 0.328, p < .001), and pain self-efficacy (rs = -0.558, p < .001). A direct effect on postoperative acute pain was exerted by pain sensitivity (effect = 0.250, p = .001), along with indirect effects through: (A) pain catastrophizing (effect = 0.028, p = .001); (B) pain self-efficacy (effect = 0.132, p = .001); and (C) the chain mediation of pain self-efficacy and pain catastrophizing (effect = 0.021, p = .008). CONCLUSIONS: The severity of postoperative acute pain can be predicted by pain self-efficacy and pain catastrophizing, and the connection between moderate pain sensitivity and postoperative acute pain severity is mediated by them. Therefore, intervention programs aimed at boosting pain self-efficacy and reducing pain catastrophizing can enhance postoperative pain outcomes for abdominal surgery patients.

Potential Threats to Human Health from Eurasian Avian-Like Swine Influenza A(H1N1) Virus and Its Reassortants.

During 2018-2020, we isolated 32 Eurasian avian-like swine influenza A(H1N1) viruses and their reassortant viruses from pigs in China. Genomic testing identified a novel reassortant H3N1 virus, which emerged in late 2020. Derived from G4 Eurasian H1N1 and H3N2 swine influenza viruses. This virus poses a risk for zoonotic infection.

Reappraise role of No. 10 lymphadenectomy for proximal gastric cancer in the era of minimal invasive surgery during total gastrectomy: a pooled analysis of 4 prospective trial.

BACKGROUND: For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. METHODS: A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. RESULTS: No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. CONCLUSIONS: LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

Safety and feasibility of laparoscopic spleen-preserving No. 10 lymph node dissection for locally advanced upper third gastric cancer: a prospective, multicenter clinical trial.

BACKGROUND: Previous retrospective studies have shown that laparoscopic spleen-preserving D2 total gastrectomy (LSTG) for advanced upper third gastric cancer (AUTGC) is safe. However, all previous studies were underpowered. We therefore conducted a prospective, multicenter study to evaluate the technical safety and feasibility of LSTG for patients with AUTGC. METHODS: Patients diagnosed with AUTGC (cT2-4a, N-/+, M0) underwent LSTG at 19 institutions between September 2016 and October 2017 were included. The number of No. 10 lymph node (LN) dissections, metastasis rates, intraoperative and postoperative complications were investigated. RESULTS: A total of 251 patients were enrolled in the study, and 242 patients were eligible for the per protocol analysis. The average numbers of No. 10 LN dissections and metastases were 2.4 and 0.1, respectively. Eighteen patients (7.4%) had No. 10 LN metastases, and among patients with advanced gastric cancer, the rate of No. 10 LN metastasis was 8.1% (18/223). pN3 status was an independent risk factor for No. 10 LN metastasis. Intraoperative complications occurred in 7 patients, but no patients required conversion to open surgery or splenectomy. The overall postoperative complication rate was 13.6% (33/242). The major complication and mortality rates were 3.3% (8/242) and 0.4% (1/242), respectively. The number of retrieved No. 10 LNs, No. 10 LN metastasis and TNM stage had no significant influence on postoperative complication rates. CONCLUSION: LSTG for AUTGC was safe and effective when performed by very experienced surgeons, this technique could be used in patients who needed splenic hilar lymph node dissection.

Identification of two novel epitopes targeting glycoprotein E of pseudorabies virus using monoclonal antibodies.

Pseudorabies virus (PRV), the agent of pseudorabies, has raised considerable attention since 2011 due to the outbreak of emerging PRV variants in China. In the present study, we obtained two monoclonal antibodies (mAbs) known as 2E5 and 5C3 against the glycoprotein E (gE) of a PRV variant (JS-2012 strain). The two mAbs reacted with wild PRV but not the vaccine strain (gE-deleted virus). The 2E5 was located in 161RLRRE165, which was conserved in almost of all PRV strains, while 5C3 in 148EMGIGDY154 was different from almost of all genotype I PRV, in which the 149th amino acid is methionine (M) instead of arginine (R). The two epitopes peptides located in the hydrophilic region and reacted with positive sera against genotype II PRV (JS-2012), which suggests they were likely dominant B-cell epitopes. Furthermore, the mutant peptide 148ERGIGDY154 (genotype I) did not react with the mAb 5C3 or positive sera against genotype II PRV (JS-2012). In conclusion, both mAb 2E5 and 5C3 could be used to identify wild PRV strains from vaccine strains, and mAb 5C3 and the epitope peptide of 5C3 might be used for epidemiological investigation to distinguish genotype II from genotype I PRV.

Effect of oral nutritional supplementation on the post-discharge nutritional status and quality of life of gastrointestinal cancer patients after surgery: a multi-center study.

BACKGROUND AND OBJECTIVES: To evaluate the effect of oral nutritional supplementation (ONS) on the postdischarge nutritional status and quality of life (QoL) of gastrointestinal cancer patients after surgery. METHODS AND STUDY DESIGN: A multi-center study was conducted on gastrointestinal cancer patients who received surgical treatment from 2013-2015. All patients were screened using the Nutrition Risk Screening 2002 (NRS 2002) to assess nutritional risk. Patients with nutritional risk were randomized into two groups: patients in the study group (n=55) were given dietary guidance and ONS, control group (n=59) received only dietary guidance. Anthropometric measurements, nutrition-related laboratory tests, and gastrointestinal function scores were also collected and analyzed using Student's t test and analysis of variance (ANOVA). In addition, the EQ-5D was used to evaluate patients' QoL. RESULTS: Compared with baseline measurements, the body weight of patients in the study group increased by 1.35±0.53 kg and 1.35±0.73 kg at 60 and 90 days, which were significantly higher than those in the control group (-1.01±0.54 kg, and -1.60±0.81 kg at 60 and 90 days). The results from ANOVA showed that only weight and BMI differed significantly between the study and control groups and also between different measurement times (p<0.01). No differences were found for the other indicators or QoL between the study groups. CONCLUSIONS: ONS may improve the weight and BMI of surgically treated gastrointestinal cancer patients postdischarge. However, these effects had little impact on patients' QoL.

MOV10 inhibits replication of porcine reproductive and respiratory syndrome virus by retaining viral nucleocapsid protein in the cytoplasm of Marc-145 cells.

Porcine reproductive and respiratory syndrome virus (PRRSV) has been a major threat to global industrial pig farming ever since its emergence in the late 1980s. Identification of sustainable and effective control measures against PRRSV transmission is a pressing problem. The nucleocapsid (N) protein of PRRSV is specifically localized in the cytoplasm and nucleus of virus-infected cells which is important for PRRSV replication. In the current study, a new host restricted factor, Moloney leukemia virus 10-like protein (MOV10), was identified as an inhibitor of PRRSV replication. N protein levels and viral replication were significantly reduced in Marc-145 cells stably overexpressing MOV10 compared with those in wild-type Marc-145 cells. Adsorption experiments revealed that MOV10 did not affect the attachment and internalization of PRRSV. Co-immunoprecipitation and immunofluorescence co-localization analyses showed that MOV10 interacted and co-localized with the PRRSV N protein in the cytoplasm. Notably, MOV10 affected the distribution of N protein in the cytoplasm and nucleus, leading to the retention of N protein in the former. Taken together, these findings demonstrate for the first time that MOV10 inhibits PRRSV replication by restricting the nuclear import of N protein. These observations have great implications for the development of anti-PRRSV drugs and provide new insight into the role of N protein in PRRSV biology.

Reduced Port Laparoscopic Distal Gastrectomy with D2 Lymphadenectomy.

BACKGROUND: Reduced port laparoscopic surgery (RPLS), as a more minimally invasive treatment alternative to conventional laparoscopic surgery (CLS), has been increasing in recent years. 1 With the accumulation of surgical experience and improvements in surgical techniques, the indication of RPLS has been gradually extended from benign diseases to malignant tumors, including gastric cancer. 2-4 However, due to the lack of counteraction and triangulation, lymphadenectomy during reduced port laparoscopic gastrectomy (RPLG) for gastric cancer was considered challenging. In this study, we report our experience performing RPLG with D2 lymphadenectomy for distal gastric cancer. METHODS: A disposable, single-incision, multiport, laparoscopic surgery trocar was used through a 3-cm incision at the umbilicus for the laparoscopist and surgeon's right hand. One 12-mm trocar was inserted at the upper-right quadrant for the surgeon's left hand. Distal gastrectomy with D2 lymphadenectomy was performed in the same manner with CLS. 5 After extracting the resected specimen through the umbilicus incision, intracorporeal Roux-en-Y or B-II gastrojejunostomy was used for reconstruction. RESULTS: RPLG with D2 lymphadenectomy was performed on five patients from April 2017 to June 2017. No intraoperative event requiring conversion to CLS or open surgery occurred. No postoperative complication was observed. The median operating time and blood loss was 166 min and 50 ml. The mean number of retrieved lymph nodes was 32.7. Postoperatively, the mean time to first flatus, soft intake, and hospital stay was 2.6, 3.5, and 6.7 days respectively. CONCLUSIONS: RPLG with D2 lymphadenectomy might be safe and feasible in selected patients.

The Granulocyte-to-Lymphocyte Ratio as a Marker of Surgical Stress and a Predictor of Postoperative Infectious Complications After Gastric Cancer Surgery: An Analysis of Patients Enrolled in a Prospective Randomized Trial.

BACKGROUND: The granulocyte-to-lymphocyte ratio (GLR) in the blood may be a useful marker of surgical stress (SS) following surgery for cancer. The aim of the present study was to compare the SS by measuring the GLR, and further study the value of the GLR in predicting postoperative infectious complications (ICs). METHODS: Data from 201 gastric cancer patients at Fujian Medical University Union Hospital who were enrolled in our prospective randomized controlled trial were extracted for this study. Blood samples to perioperatively measure the GLR were routinely taken. Additional external validation was performed using the dataset (n = 135) from Nanfang Hospital who were enrolled in the same trial. RESULTS: Patients undergoing either laparoscopic or open resection showed a similar preoperative GLR, as well as similar GLRs, on postoperative days (PODs) 1 and 3. The GLR on POD 5 was lower in the laparoscopic group compared with the open group (p = 0.014), and the optimal predictive GLR thresholds of postoperative ICs in both the laparoscopic and open groups were the same on POD 5, i.e. 6.5 and 7.4, respectively. The GLR on POD 5 was identified as an independent factor for postoperative ICs in both the laparoscopic and open groups. Similar results were found in the validation dataset. CONCLUSION: The GLR status not only correlates with SS but may also be a reliable predictor of ICs for gastric cancer patients after gastrectomy. The ideal GLR thresholds on POD 5 for ICs following laparoscopic and open gastrectomy are 6.5 and 7.4, respectively.

An automatically contamination-avoiding technique for intracorporeal esophagojejunostomy using a transorally inserted anvil during laparoscopic total gastrectomy for gastric cancer.

BACKGROUND: Intracorporeal Roux-en-Y esophagojejunostomy during laparoscopic total gastrectomy for gastric cancer remains a challenging manipulation due to the uncontrolled direction of the jejunal side or unintended embedded tissues, although several methods have been introduced. In this study, we simplified the procedure based on a surgical string fixing technique using a transorally inserted anvil (OrVil™; Covidien Ltd., Mansfield, MA, USA). METHODS: From March 2012 to September 2013, 14 consecutive patients underwent simplified intracorporeal Roux-en-Y esophagojejunostomy using OrVil™ during laparoscopic total gastrectomy for gastric cancer at our hospital. Clinicopathologic characteristics and surgical outcomes of these patients were retrospectively analyzed. RESULTS: All of the procedures were successful completed with no complication or conversion to open surgery. The mean overall operative time was 193.8 ± 41.8 min, whereas the mean reconstruction time was 32.6 ± 4.6 min. The mean estimated blood loss was 105.7 ± 65.4 ml. The mean diameter of anastomosis measured by upper gastrointestinal contrast X-ray test at 1 month after operation was 2.3 cm. During a median follow-up period of 12 months, neither local recurrence nor anastomosis-related morbidity was observed. CONCLUSIONS: Our preliminary results suggested that this automatically contamination-avoiding technique based on a surgical-string-fixing strategy using OrVil™ during laparoscopic total gastrectomy for gastric cancer might be feasible and safe and provide a simple solution for intracorporeal Roux-en-Y esophagojejunostomy.

MicroRNA-338-3p inhibits colorectal carcinoma cell invasion and migration by targeting smoothened.

OBJECTIVE: To investigate the regulative effect of microRNA-338-3p on colorectal carcinoma cell invasion and migration. METHODS: The microRNA-338-3p expression pattern of colorectal carcinoma tissues and cell lines was detected by real-time reverse transcriptase polymerase chain reaction. The protein level of smoothened was detected by western blot analysis. Furthermore, colorectal carcinoma cells were pretreated with or without anti-smoothened-small interfering ribonucleic acid prior to the addition of pre-microRNA-338-3p or anti-microRNA-338-3p. The status of colorectal carcinoma cell invasion and that of migration were detected by transwell assay and wound healing assay, respectively. RESULTS: The expression of microRNA-338-3p was significantly down-regulated in colorectal carcinoma tissues in comparison with those in the adjacent non-tumorous tissues, and the value was negatively related to advanced tumor, node, metastasis stage and local invasion. The expression of microRNA-338-3p in colorectal carcinoma cells transfected with pre-microRNA-338-3p p was significantly increased. Furthermore, over-expression of microRNA-338-3p inhibited the expression of smoothened protein in colorectal carcinoma cells, which showed obviously suppressed invasion and migration ability. The expression of microRNA-338-3p in colorectal carcinoma cells transfected with anti-microRNA-338-3p was significantly decreased. Moreover, the down-regulated expression of microRNA-338-3p caused the up-regulated expression of smoothened protein in colorectal carcinoma cells, which showed significantly enhanced invasion and migration ability. However, anti-smoothened-small interfering ribonucleic acid largely, but not completely, reversed the effects induced by blockage of microRNA-338-3p, suggesting that the regulative effect of microRNA-338-3p on colorectal carcinoma cell invasion and migration was indeed mediated by smoothened. Additionally, smoothened was identified as a direct target of microRNA-338-3p by luciferase assay. CONCLUSIONS: MicroRNA-338-3p could inhibit colorectal carcinoma cell invasion and migration by inhibiting smoothened expression.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

BACKGROUND: Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. RESULTS: Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. CONCLUSIONS: Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

Construction of lentivirus-based inhibitor of hsa-microRNA-338-3p with specific secondary structure.

AIM: To construct a lentivirus-based inhibitor with specific secondary structure that could exert long-term suppression on microRNA-338-3p (miR-338-3p), thus elucidating its molecular function in colorectal carcinoma cells. METHODS: The miR-338-3p inhibitor sequence was synthesized and inserted into pLV-THM plasmid. HEK-293T cells were co-transfected with the lentiviral vectors pLV-THM-miR-338-3p-inhibitor, psPAX2, and pMD2.G. The supernatant containing the lentivirus particles was harvested to determine the viral titer, and then used to infect colorectal carcinoma-derived SW-620 cells. eGFP(+) cells were sorted using flow cytometry. The expression of miR-338-3p in SW-620 cells was determined with real-time RT-PCR, and the expression of the smoothened (SMO) protein was detected using Western blot analysis. The migration ability of the transfected SW-620 cells was assessed with transwell assay. RESULTS: Restriction endonuclease analysis and DNA sequencing demonstrated that the lentiviral vector pLV-THM-miR-338-3p-inhibitor was successfully constructed. The expression of miR-338-3p in SW-620 cells was significantly decreased by infection with the lentivirus pLV-THM-miR-338-3p-inhibitor. Moreover, the down-regulated expression of miR-338-3p caused up-regulated expression of the SMO protein in SW-620 cells, which showed significantly enhanced migration in transwell assay. CONCLUSION: The construction of the lentiviral vector pLV-THM-miR-338-3p-inhibitor with specific secondary structure provides a basis for further studies the molecular function of miR-338-3p in colorectal carcinoma. miR-338-3p may suppress SMO gene expression and thereby inhibit colorectal carcinoma migration.

[The safety and long-term survival after laparoscopic surgery versus open surgery for colon cancer].

OBJECTIVE: To evaluate the short-term outcomes and 5-year recurrence, overall survival, and disease-free survival of laparoscopic assisted surgery for colon cancer. METHODS: The clinical and pathologic data were compared between the patients who underwent colectomy during March 2003 to July 2008 and assigned in laparoscopic group (n = 92) and open group (n = 285) according the surgical approach. The 5-year overall survival, disease-free survival, and recurrence rate were analyzed for all patients who were followed-up for more than 36 months in either of the groups. RESULTS: The laparoscopic colectomy was associated with manifested less blood loss (50(50) ml) (Z = -8.292, P < 0.01), early return of bowel function (the evacuation time was (3.0 ± 1.0) days, and the meal time after operation was (4.0 ± 1.3) days) (t = -6.475 and -4.871, P < 0.01), and longer length (cm) of distal resection margin ((10 ± 4) cm vs. (9 ± 4) cm, t = 3.527, P = 0.000). The 5-year overall survival of the laparoscopic group and the open group were 63.6% and 61.8% respectively. The 5-year disease-free survival of the I-III stage patients in the laparoscopic group and the open group were 69.5% and 65.5% respectively, and the local recurrence were 8.7% and 13.6% (all P > 0.05). CONCLUSION: The laparoscopic colectomy for colon cancer is safe in short-term clinical results and non-inferior to the open colectomy in long-term oncological outcomes.

[Effects of Polystyrene Nanoplastics (PS-NPs) on the Physiology of Allium sativum L.]

The pollution of micro/nanoplastics in the natural environment is becoming increasingly serious, but the potential effects of nanoplastics on crops remain unclear. In the present study, the effects of polystyrene nanoplastics (PS-NPs) with a particle size of 80 nm on the chlorophyll content, antioxidant enzyme activity, and nutritional quality of Allium sativum L. were explored via hydroponic culture. The results showed that the chlorophyll contents in leaves of A. sativum treated with PS-NPs were significantly lower than those in the control, indicating that the synthesis of chlorophyll was inhibited. The superoxide dismutase (SOD), ascorbate peroxidase (APX) activities, and proline contents in leaves of A. sativum initially increased but then decreased with the increase in ρ(PS-NPs). The activity of guaiacol peroxidase (POD) increased with the increase in ρ(PS-NPs) for 10 days of treatment; however, it was inhibited for 20 days of treatment. The malondialdehyde (MDA) content increased with the rise in ρ(PS-NPs). When ρ(PS-NPs) increased to 100 mg·L-1, the MDA content in leaves of A. sativum increased by 43.24% and 89.70% for 10 and 20-day treatments, respectively, compared with those in the control. Meanwhile, the contents of soluble protein, soluble sugar, and vitamin C were higher than those in the control for 10-day treatments; however, the vitamin C content decreased by 26.53% after 20 days of treatment. These results indicated that PS-NPs had a significant oxidative stress on A. sativum, and a high concentration of PS-NPs stress would have deleterious effects on the nutritional quality of A. sativum.

cGAS Restricts PRRSV Replication by Sensing the mtDNA to Increase the cGAMP Activity.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that causes great economic losses globally to the swine industry. Innate immune RNA receptors mainly sense it during infection. As a DNA sensor, cyclic GMP-AMP synthase (cGAS) plays an important role in sensing cytosolic DNA and activating innate immunity to induce IFN-I and establish an antiviral cellular state. In contrast, the role of innate immune DNA sensors during PRRSV infection has not been elucidated. In this study, we found that cGAS facilitates the production of IFN-ß during PRRSV infection. Western blot and virus titer assays suggested that cGAS overexpression suppressed the replication of multiple PRRSV strains, while knockout of cGAS increased viral titer and nucleocapsid protein expression. Besides, our results indicated that the mitochondria were damaged during PRRSV infection and leaked mitochondrial DNA (mtDNA) into the cytoplasm. The mtDNA in the cytoplasm co-localizes with the cGAS, and the cGAMP activity was increased when the cGAS was overexpressed during PRRSV infection. Furthermore, the cGAMP also possesses an anti-PRRSV effect. These results indicate for the first time that cGAS restricts PRRSV replication by sensing the mtDNA in the cytoplasm to increase cGAMP activity, which not only explains the molecular mechanism by which cGAS inhibits PRRSV replication but also provides research ideas for studying the role of the cGAS-STING signaling pathway in the process of RNA virus infection.

MicroRNA-221 inhibits CDKN1C/p57 expression in human colorectal carcinoma.

AIM: To investigate the regulatory effect of microRNA-221 (miR-221) on CDKN1C/p57 expression in colorectal carcinoma (CRC). METHODS: Thirty four CRC and adjacent non-tumorous tissue samples were collected individually. Total RNA and protein were isolatedand from these samples and four human CRC-derived cell lines (including HT-29, Lovo, SW-480 and Caco2). MiR-221 expression was examined using real-time RT-PCR. CRC cells were treated with or without anti-p57-siRNA prior to the addition of pre-miR-221 or anti-miR-221. The mRNA and protein levels of CDKN1C/p57 were examined using semi-quantitative RT-PCR and Western blot, respectively. CRC cell proliferation and apoptosis were assessed using MTT assay and flow cytometry, respectively. The CDKN1C/p57 3'-UTR fragment was amplified using PCR from the genomic DNA of human colon cells and inserted into a luciferase reporter construct. The reporter construct was then transfected into CRC cells together with pre-miR-221 or anti-miR-221, and the luciferase activity in the transfected cells was examined. RESULTS: MiR-221 expression was significantly up-regulated in 90% of CRC samples compared to that in the adjacent non-tumorous tissue, and the expression level was positively correlated to an advanced TNM stage and local invasion. There was no significant difference in CDKN1C/p57 mRNA expression between CRC and corresponding non-tumorous tissues, whereas CDKN1C/p57 protein expression was markedly decreased in the CRC samples. A significant inverse correlation between miR-221 and CDKN1C/p57 expression was found in CRC cells. Moreover, a miR-221-specific inhibitor significantly increased CDKN1C/p57 protein expression in CRC cells. Anti-miR-221 markedly inhibited CRC cell proliferation and induced apoptosis. This inhibitory effect was abolished by pretreatment with anti-p57-siRNA, suggesting that the inhibition was mediated by CDKN1C/p57. A significant increase of the luciferase activity was observed in CRC cells co-transfected with the luciferase reporter construct and anti-miR-221. CONCLUSION: MiR-221 binds to the target site in the 3'-UTR of the CDKN1C/p57 mRNA to inhibit CDKN1C/p57 expression by post-transcriptional gene silencing to promote CRC occurrence and progress, therefore serving as a potential therapeutic target for the prevention and treatment of CRC.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2021.

There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow-up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non-metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third-line to the first-line of treatment for different patient groups with detailed notes are provided.