[Rethinking the scope of lymphadenectomy after neoadjuvant immunotherapy for locally advanced gastric cancer].

Radical gastrectomy is the core of comprehensive treatment for patients with locally advanced gastric cancer,while reasonable and standardized lymphadenectomy is the key to radical gastrectomy.With the continuous development of treatment methods and therapeutic drugs for advanced gastric cancer, it is worth exploring whether the scope of lymphadenectomy needs to be changed. Neoadjuvant immunotherapy has brought a new breakthrough for locally advanced gastric cancer, increased pathological complete response rate, reduced clinical stage of tumors, and increased radical surgical resection rate, but it has not brought long-term benefits to patients. Lymph nodes play an important role in human anti-tumor immune response, and some basic studies suggest that preserving some normal lymph nodes may be more helpful to enhance the efficacy of immunotherapy. Thus, in the era of immunotherapy, the extent of lymph node dissection for locally advanced gastric cancer needs to balance continuous drug benefits, patient quality of life, and survival benefits, awaiting further high-quality clinical research for determination. Questions such as how to differentiate between normal and metastatic lymph nodes, how to rationally preserve normal lymph nodes, and whether preserving partial lymph node function can lead to greater benefits for patients from immunotherapy warrant further exploration.

[The Development of SpCas9 Variants with High Specificity and Efficiency Based on the HH Theory].

Streptococcus pyogenes Cas9 (SpCas9) is the most popular tool in gene editing; however, off-target mutagenesis is one of the biggest impediments in its application. In our previous study, we proposed the HH theory, which states that sgRNA/DNA hybrid (hybrid) extrusion-induced enhancement of hydrophobic interactions between the hybrid and REC3/HNH is a key factor in cleavage initiation. Based on the HH theory, we analyzed the interactions between the REC3 domain and hybrid and obtained 8 mutant sites. We designed 8 SpCas9 variants (V1-V8), used digital droplet PCR to assess SpCas9-induced DNA indels in human cells, and developed high-fidelity variants. Thus, the HH theory may be employed to further optimize SpCas9-mediated genome editing systems, and the resultant V3, V6, V7, and V8 SpCas9 variants may be valuable for applications requiring high-precision genome editing.

[Influence of sleep fragmentation in infancy and toddler period on emotional and behavioral problem at the age of 6 years: a birth cohort study].

Objective: To investigate the influence of sleep fragmentation in infancy and toddler period on emotional and behavioral problems at the age of 6 years. Methods: Using a prospective cohort design, 262 children were extracted from mother-child birth cohort recruited from May 2012 to July 2013 in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Children's sleep and physical activities were assessed using actigraphy at 6, 12, 18, 24, and 36 months of age, from which the sleep fragmentation index (FI) at each follow-up point was calculated. Children's emotional and behavioral problems at 6 years of age were assessed using the strengths and difficulties questionnaire. Group-based trajectory model was applied to determine sleep FI in infancy and toddler period trajectory groups with Bayesian information criteria being used to determine the best fitting model. Children's emotional and behavioral problems between groups were examined with independent t test and linear regression models, etc. Results: A total of 177 children, with 91 boys and 86 girls, were included in the final analysis and were divided into 2 groups: high FI group (n=30) and low FI group (n=147). Compared with children in the low FI group, those in the high FI group presents with higher total difficulties score and higher hyperactivity or inattention score ((11.0±4.9) vs. (8.9±4.1), (4.9±2.7) vs. (3.7±2.3) scores, t=2.17, 2.23, both P<0.05, respectively), with the differences remaining significant after adjusting for covariates (t=2.08, 2.09, both P<0.05 respectively). Conclusion: High sleep fragmentation in infancy and toddler period is associated with more emotional and behavioral problems, especially hyperactivity or inattention problems, at 6 years of age.

[Study on risk factors of abnormal pulmonary function among dust-exposed workers and prediction model].

Objective: To explore the influencing factors of abnormal pulmonary function in dust-exposed workers and establish the risk prediction model of abnormal pulmonary function. Methods: In April 2021, a total of 4255 dust exposed workers from 47 enterprises in 2020 were included in the study. logistic regression was used to analyze the influencing factors of abnormal pulmonary function in dust-exposed workers, and the corresponding nomogram prediction model was established. The model was evaluated by ROC curve, Calibrationpolt and decision analysis curve. Results: logistic regression analysis showed that age (OR=1.03, 95%CI=1.02~1.05, P<0.001) , physical examination type (OR=4.52, 95%CI=1.69~12.10, P=0.003) , dust type (Comparison with coal dust, Cement dust, OR=3.45, 95%CI=1.45~8.18, P=0.005, Silica dust (OR=2.25, 95%CI=1.01~5.03, P=0.049) , blood pressure (OR=1.63, 95%CI=1.22~2.18, P=0.001) , creatinine (OR=0.08, 95%CI=0.05~0.12, P<0.001) , daily exposure time (OR=1.06, 95%CI=1.10~1.12, P=0.034) and total dust concentration (OR=1.29, 95%CI=1.08~1.54, P=0.005) were the influencing factors of abnormal pulmonary function. The area under the ROC curve of risk prediction nomogram model was 0.764. The results of decision analysis curve showed that the nomogram model had reference value in the prevention and intervention of abnormal pulmonary function when the threshold probability exceeded 0.05. Conclusion: The accuracy ofthe nomogram model constructed by logistic regression werewell in predicting the risk of abnormal lung function of dust-exposed workers.

[Effect of rebamipide on the acute gouty arthritis in rats induced by monosodium urate crystals].

OBJECTIVE: To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal. METHODS: Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1ß、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured. RESULTS: In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P < 0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P < 0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P < 0.001). After 24 h of model induced, the levels of IL-1ß, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1ß: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) µg/L, P < 0.001]. CONCLUSION: Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

[Efficacy and safety of intraoperative ultrasound-assisted neuroendoscopy in the treatment of hypertensive intracerebral hemorrhage via transsylvian approach].

Objective: To explore the efficacy and safety of intraoperative ultrasound-assisted neuroendoscopy for treating hypertensive intracerebral hemorrhage (HICH) via lateral fissure and insula approach. Methods: The clinical data of 66 patients with HICH in basal ganglia who underwent intraoperative ultrasound-assisted neuroendoscopy via lateral fissure and insula approach for hematoma evacuation were retrospectively analyzed, including operative data and follow-up results. All patients had no brain hernia before operation. The hematoma was located by the ultrasound and then the path into the hematoma cavity was determined. Meanwhile, the residual hematoma was also detected by using the ultrasound. The clearance rate of hematoma was observed by CT. Barthel index was used to evaluate the activity of daily living. Results: The amount of residual hematoma was less than 10% in 63 ases and 10%-20% in 3 cases. There were 11 cases of postoperative pneumonia, of whom 9 cases underwent percutaneous tracheotomy. Rebleeding occurred in 2 cases, but the amount was small, and there was no need for reoperation. Meanwhile, there was 1 case of secondary intracranial infection and 1 case of secondary hydrocephalus. No case of cerebral contusion was reported. Half a year after the operation, Barthel Index grading showed that there were 3 cases of grade I, 25 cases of grade Ⅱ, 34 cases of grade Ⅲ, 3 cases of grade Ⅳ and 1 case of death, respectively. Conclusions: Intraoperative ultrasound-assisted neuroendoscopy via lateral fissure and insula approach can improve the efficacy and safety of treatment for HICH.

Up-regulated ONECUT2 and down-regulated SST promote gastric cell migration, invasion, epithelial-mesenchymal transition and tumor growth in gastric cancer.

OBJECTIVE: Gastric cancer is a common malignancy, with high metastasis and poor prognosis. Our purpose was to explore potential molecular mechanisms of gastric cancer. PATIENTS AND METHODS: A total of 10 pairs of gastric cancer tissues and adjacent normal gastric tissues were collected for RNA sequencing (RNA-seq), followed by differential expression analysis. Combining qRT-PCR results, two novel genes were selected for in-depth analysis, including up-regulated ONECUT and down-regulated SST. To investigate the effects of ONECUT and SST on the biological behaviors of gastric cancer cells, gastric cancer cell lines were transfected by ONECUT2 knockdown and SST overexpression. Afterwards, cell migration and invasion were examined using transwell assays, and the expressions of epithelial-mesenchymal transition (EMT)-related proteins were measured by Western blot analysis. Furthermore, cell viability was detected by CCK-8 assay. Finally, tumorigenicity in nude mice was performed. RESULTS: Gastric cancer cell migration and invasion were inhibited in BGC823 cells transfected by shONECUT2. Similar results were observed in SST overexpression in MGC803 cells. Silencing ONECUT2 or overexpressing SST reduced the expressions of mesenchymal markers (N-cadherin and vimentin), STAT3, fibronectin, Wnt2, ß-catenin and increased epithelial marker (E-cadherin), p-STAT3, smad2/3, α-catenin protein levels. In addition, inhibiting ONECUT2 or elevated SST suppressed tumor cell viability in vitro. Moreover, ONECUT2 silencing or elevated SST significantly inhibited tumor growth in vivo. CONCLUSIONS: Up-regulated ONECUT2 and down-regulated SST promote gastric cell migration, invasion, epithelial-mesenchymal transition and tumor growth in gastric cancer.

[Short-term efficacy of robotic-assisted total mesorectal excision with and without lateral lymph node dissection for mid-low advanced rectal cancer: a propensity score matching analysis].

Objective: To evaluate the feasibility, safety and efficacy of robotic-assisted lateral lymph node dissection for mid-low advanced rectal cancer. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) age between 18 and 80 years old; (2) rectal adenocarcinoma diagnosed by pathology; (3) without distant metastasis by preoperative CT or MRI; (4) patients underwent robotic-assisted total mesorectal resection (TME). Exclusion criteria: (1) conversion to open surgery; (2) multiple primary tumors; (3) patients underwent combined multiple organ resection. According to the above criteria, 137 patients undergoing robotic-assisted mid-low rectal cancer resection in the First Affiliated Hospital of Xi'an Jiaotong University from December 2016 to April 2019 were enrolled. Ninety-seven cases underwent robotic-assisted total mesorectal excision (TME group) and 40 underwent robotic-assisted total mesorectal resection with lateral lymph node dissection (LLND) (TME+LLND group, pelvic LLND was performed with neurovascular guidance to retain pelvic autonomic nerves in the order of the left side the first and then the right side). The propensity score matching of 1:1 was performed with R software, based on age, sex, BMI, ASA classification, distance from tumor to the anal verge, preoperative chemoradiotherapy history, preoperative abdominal surgery history, the size of tumors and TNM stage. The operative indicators, postoperative recovery, pathology and postoperative complications within 30 days were compared between the two groups. Results: A total of 72 cases were successfully matched (36 in each group), and there were no statistically significant differences in baseline data between the two groups (all P>0.05). The operation time of TME+LLND group was significantly longer than that of TME group [275.0 (180-405) minutes vs. 220.0 (140-320) minutes, Z=-3.680, P<0.001], while there were no statistically significant differences in blood loss during operation, time to postoperative first flatus, postoperative hospital stay, total hospital cost, tumor differentiation, and distal resection length of margin (all P>0.05). Circumferential resection margin was all negative in both groups. The number of harvested lymph modes in the TME+LLND groups was higher than that in the TME group [26 (18-37) vs. 14 (9-36), Z=-6.407, P<0.001]. In addition, there were no statistically significant differences in postoperative morbidity and Clavien-Dindo classification of complication within 30 days between the two groups (both P>0.05). Conclusions: Although robotic lateral lymph node dissection requires longer operation time, it is a feasible, safe and effective procedure.

[Risk factor analysis of perioperative complications in patients with radical gastrectomy for gastric cancer].

Objective: To identify the risk factors of perioperative complications after radical gastrectomy for gastric cancer. Methods: A retrospective case-control study was performed. Case inclusion criteria: (1) patients undergoing radical gastrectomy (D2); (2) primary gastric cancer without distant organ metastasis confirmed by postoperative pathology; (3) no neoadjuvant chemotherapy before surgery. Patients with peritoneal tumor dissemination found during operation, undergoing palliative operation due to distant metastasis, and undergoing combined organ resection and those without complete clinicopathological data were excluded. According to the above criteria, 426 patients with gastric cancer at our department from January 2015 to June 2017 were included in this study. Of 426 patients, 285 were male and 141 were female with a mean age of (55.4±9.7) years. According to the "Japan Clinical Cancer Research Group (JCOG) classification criteria for postoperative complications of gastric cancer", patients with grade II and higher complications were classified as complication group, and patients with no complication or grade I complication were classified as non-complication group. Baseline data were compared between two groups. Associations of perioperative complication with gender, age, body mass index, preoperative routine laboratory test, American Society of Anesthesiologists (ASA) classification, activities of daily living (ADL) assessment, past medical history as well as preoperative conditions (hypertension and/or diabetes), surgical resection procedure, incision type, operation time, intraoperative blood loss/body mass ratio were examined. Univariate analysis was performed using χ(2) test and the Wilcoxon rank sum test to screen the statistically significant variables associated with perioperative complications. The significant variables were included in multivariate logistic regression analysis to identify risk factors of perioperative complication. Results: Grade II or higher complications after surgery were developed in 97 patients (22.8%), which included anastomotic leakage in 18 cases (4.2%), postoperative bleeding in 9 cases (2.1%), abdominal abscess in 5 cases (1.2%), intestinal obstruction in 5 cases (1.2%), pancreatic leakage in 1 case (0.2%), and other adverse events in 59 cases (13.8%). Univariate analysis suggested that the gender, age, ADL, incision type, intraoperative blood loss/body mass ratio, and operation time were associated with perioperative complication (all P<0.05). Multivariate analysis revealed that elder age (OR=1.033, 95% CI:1.013-1.053, P=0.013), incision type of laparotomy (OR=2.091, 95% CI:1.247-3.508, P=0.004), longer operation time (OR=1.004, 95% CI:1.001-1.007, P=0.001) and higher ratio of intraoperative blood loss/body mass (OR=1.100, 95% CI: 1.039-1.163, P=0.031) were risk factors for postoperative complications. Conclusion: Attention should be paid to those cases with elder age, laparotomy incision, longer operation time and higher ratio of intraoperative blood loss/body mass, and perioperative management after gastrectomy should be improved.

[Study on the relationship between age-related hearing loss and cognitive impairment].

Objective: To investigate the correlation between age-related hearing loss and cognitive impairment. Methods: 201 elderly patients, who were admitted to the Department of Otorhinolaryngology of Peking University People's Hospital from March 1, 2017 to March 31, 2017, were evaluated with hearing screening and the Montreal Cognitive Assessment Scale. Among them, 101 were female and 100 were male, aged 60-90 years old. Taking the cognitive level as the dependent variable, and taking the age, sex, education, occupation, marital status, residence, and average hearing loss (average hearing threshold of 500, 1 000, 2 000, and 4 000 Hz), as well as the length of conscious hearing loss as the independent variables, the single factor analysis and multivariate linear regression analysis were used to screen the main factors affecting the cognitive level of the elderly. Results: Of the 201 elderly patients, 39 had normal hearing, 65 had mild hearing loss, 80 had moderate hearing loss, 16 had severe hearing loss, and 1 had profound hearing loss. The average degree of hearing loss was the influencing factor of cognitive impairment, and it mainly affected the directional force and abstract ability in the cognitive domains (P<0.05); The age, self-reported hearing loss, years of education, marital status, past ear diseases, and hypertension were relatively independent factors that affected the cognitive level(P<0.05). Conclusions: Age-related hearing loss is the risk factor for the cognitive impairment, especially for abstraction and orientation, in the elderly. The self-reported hearing loss is an independent risk factor for cognitive impairment.

[Analysis on chromosome aberration rate, micronucleus cell rate and related factors of 3021 radiation workers in Changzhou].

Objective: To investigate the chromosomal aberration rate, micronucleus cell rate and the related factors of radiation workers in Changzhou, provide evidence for the occupational health and safety of radiation workers. Methods: Descriptive analysis of the chromosomal aberration rate, micronucleus cell rate and the related factors of 3021 radiation workers who conducted occupational health examination in the Changzhou Center for Disease Control and prevention in 2017, multivariate logistic regression was used to analyze the data. Results: The abnormal rate of chromosome aberration and micronucleus cells of 3021radiation workers in Changzhou were 1.32% and 3.34% respectively. The results of multivariate logistic regression showed that the exposure year (OR=1.501, 95%CI:1.078~2.089, P=0.016) was a risk factor for chromosome aberration. The risk of chromosome aberration in radiation therapy (OR=6.417, 95%CI:1.360~30.280, P=0.019) and interventional radiology (OR=4.598, 95%CI:1.688~12.524, P=0.003) was higher than that of industrial application. the exposure year (OR=1.245, 95%CI:1.007~1.539, P=0.043) is also a risk factor for micronucleus cell rate. The micronucleus cell rate abnormality Risk of nuclear medicine (OR=3.934, 95%CI:1.305~11.858, P=0.015) , radiation therapy (OR=3.802, 95%CI:1.101~13.128, P=0.035) , and interventional radiology (OR=2.953, 95%CI:1.324~6.584, P=0.008) is higher than industrial application. Conclusion: The chromosome aberration rate and micronucleus rate of workers who are exposed to low dose ionizing radiation for long time are related to the exposure year of radiation workers and the occupational categories involved.

Effects of HIF-1α on diabetic retinopathy angiogenesis and VEGF expression.

OBJECTIVE: To investigate the effect of hypoxia inducing factor (HIF)-1α on the expression of vascular endothelial growth factor (VEGF) and angiogenesis in diabetic retinopathy. PATIENTS AND METHODS: 8-week healthy SD rats were used for the experiments. Under systemic anesthesia condition, control rats received a saline injection into the left ocular body (control A group), and 2 µl antisense oligonucleotides (ASODN) (10 µmol/L) into right eye (control B group). Model rats received a saline injection into the left eye (model A group), and 2 µl ASODN (10 µmol/L) into the right eye (model B group). Rats received an intraocular injection of HIF-1α ASODN for 2, 4, and 6 weeks (A1, A2, A3, B1, B2, B3, respectively). Retinal vessel development was observed by ADP staining. Vascular endothelial cells penetrating retinal inner membrane were counted. Immunohistochemistry was used to detect expressions of VEGF and HIF-1α proteins in the retina. RESULTS: Prominent angiogenesis and hyperplasia were found in model A group. Relatively fewer newly formed vessels were shown in model group B. However, no significant change of retinal vascular morphology was presented in control group. Of note, the vascular endothelial cell counts, VEGF and HIF-1α contents were significantly increased in model group (p < 0.05). After treatment with HIF-1α ASODN, lower endothelial cell counts was found in model B group (p < 0.05 comparing to model A). VEGF expression in model B group was significantly decreased, among which, model B3 was observed with lower cell counts than model B1 or B2 (p < 0.05 comparing to model A). Injection of HIF-1α ASODN significantly suppressed HIF-1α level in model B in a time-dependent manner. CONCLUSIONS: Retinal angiogenesis is closely related with increasing level of HIF-1α. Inhibition of HIF-1α suppressed VEGF expression and deterred angiogenesis in a time-dependent manner. This provided novel insights for treating diabetic retinopathy.

MiRNA-93 functions as an oncogene in glioma by directly targeting RBL2.

OBJECTIVE: Glioma is a tumor of the brain. Although the clinical regimens and surgical techniques for glioma have improved, therapies of advanced glioma remain challenging, carrying dismal overall survival and therapeutic success rates. Evidence has shown that miRNAs played important roles in glioma development. The current study aimed at investigating the function of a novel cancerogenic miRNA, miR-93, in glioma progression by investigating the expression and mechanism of it. PATIENTS AND METHODS: qRT-PCR was conducted to assess the miR-93 expression and the mRNA expression of target gene in glioma tissues and cells. The invasion and migration abilities of the glioma cells were determined by transwell assays. Luciferase reporter assay was performed to confirm the target of miR-93. RESULTS: The results indicated that miR-93 expression in glioma tissues and cells was increased significantly than that in normal brain tissues and cells. Furthermore, miR-93 promoted glioma cell migration and invasion. RBL2 was recognized as a direct target of miR-93 in glioma cells, and overexpression of RBL2 could reverse the stimulative effect of miR-93 in glioma cell. CONCLUSIONS: The above findings suggested that miR-93 together with RBL2 could be diagnostic targets and novel prognostic markers for glioma.

Very high external quantum efficiency and wall-plug efficiency 527 nm InGaN green LEDs by MOCVD.

We demonstrate very high luminous efficacy InGaN-based green light-emitting diodes (LEDs) grown on c-plane patterned sapphire substrates (PSS) using metal organic chemical vapor deposition (MOCVD). The 527 nm green LEDs show a peak external quantum efficiency (EQE) of 53.3%, a peak wall-plug efficiency (WPE) of 54.1% and a peak luminous efficacy of 329 lm/W, respectively. A high EQE of 38.4%, a WPE of 32.1% and a very low forward voltage of 2.86 V were obtained at a typical working current density of 20 A/cm2. By operating low cost green LEDs at a low current density, our devices (0.5 mm2) demonstrating an EQE and a WPE higher than 50% and an efficacy of 259 lm/W at 4 A/cm2 with an output power of 24 mW. High crystal quality of the InGaN/GaN MQWs was characterized by X-ray diffraction (XRD) and the advantage of the epitaxy design was investigated by APSYS software simulation. These results provide a simple way to achieve very high efficiency InGaN green LEDs.