Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective:To investigate the genetic risk factors and prognosis of 190 patients with myelodysplastic syndrome(MDS). Methods:The clinical data of 190 patients with MDS admitted to the Department of Hematology,The First Affiliated Hospital of Chongqing Medical University from January 2015 to October 2020 were analyzed retrospectively,and the genetic background and survival curve of the patients were also analyzed. Results:MDS patients with higher risk according to International Prognostic Score System(IPSS)stratification at the time of initial diagnosis had more frequent and complex types of gene mutation and chromosomal abnormalities,indicating poor prognosis.The choice of treatment is associated with the prognosis of MDS patients with intermediate risk(IPSS stratification),and the relative risk of the overall survival rate of patients treated with hypomethylating agents is higher than that of patients on concomitant medication. Conclusion:MDS patients with higher-risk(IPSS stratification)have more complex genetic risk factors and lower survival rate than those with lower-risk(IPSS stratification).MDS patients with multiple genetic risk factors have a poor prognosis,and the type of gene mutation is a predictor of prognosis.

Objective:To analyze the epidemiologic characteristics of environmental samples of avian influenza virus in Fujian province from 2017 to 2021, and provide a reference for the prevention and control of avian influenza.Methods:Six types of specimens were collected from four types of environments in six cities in Fujian province. And the specimens were subjected to nucleic acid detection for influenza A, subtypes H5, H7 and H9 by fluorescence quantitative PCR, and the results were analyzed statistically with descriptive epidemiological methods.Results:From 2017 to 2021, a total of 4 214 samples were collected from 6 cities, of which the positive rate of avian influenza virus was 41.53%, and the positive rates of H5, H7 and H9 subtypes were 2.33%, 1.16% and 23.16%, respectively. The positive rate for mixed subtypes of H5 and H7 was 0.05%, the positive rate for mixed subtypes of H5 and H9 was 1.83%, the positive rate for mixed subtypes of H7 and H9 was 0.83%, the positive rate for mixed subtypes of H5, H7 and H9 was 0.09%, and the positive rate of A-type unclassified was 12.08%. The difference in avian influenza virus detection among different monitoring places ( χ2=517.57, P<0.001), different types of specimens( χ2= 51.58, P<0.001), and different cities ( χ2=458.34, P<0.001) was statistically significant. Among different monitoring places, the positive rate of avian influenza virus in urban and rural live poultry markets was the highest. The highest rate of positive detection was found in specimens from the cage surface, cleaning poultry sewage and poultry chopping board surface, with 48.09%, 47.34% and 45.66%, respectively. In terms of different cities, Sanming city had the highest positivity rate (56.00%), while Zhangzhou city had the lowest positivity rate(3.34%). And the positive rate was higher from November to February of the next year and June to August each year. Conclusions:The overall positive rate of avian influenza viruses in Fujian province was relatively high, with H9 subtype accounting for the main proportion. The monitoring of avian influenza viruses in winter, spring and summer should be strengthened. And effective measures should be taken to deal with avian influenza especially in urban and rural live poultry markets.

Objective:To study the effect of different crystalloid resuscitation on renal function in septic shock rabbits, and to provide a theoretical basis for the choice of crystalloid for clinical fluid resuscitation.Methods:Thirty-six healthy male New Zealand white rabbits were divided into six groups by random number table: control group, model group, and four crystalloid groups including normal saline (NS) group, lactate Ringer solution (LR) group, acetate Ringer solution (AR) group, and sodium potassium magnesium calcium glucose injection (SPMCG) group, with 6 rabbits in each group. Rabbits were infused with Escherichia coli lipopolysaccharide (LPS) 500 μg/kg via the marginal ear vein (infused at a constant speed within 20 minutes), and then continued to infuse in an increase of 300 μg/kg every 10 minutes, the maximum dose was 2 mg/kg, until the mean arterial pressure (MAP) dropped to 60% of the basal value, the septic shock model was considered to be successfully reproduced. The rabbits in the control group were not injected with LPS, and other operations were the same as in the model group. Different crystalloid groups were given crystal solution immediately after modeling for resuscitation (predetermined fluid volume 60 mL/kg, transfusion within 3 hours). The volume stress test was performed every hour to guide the fluid volume, and the stroke volume index increase rate (ΔSVI) < 15% was the end point of resuscitation. The control group and the model group were given NS 4 mL·kg -1·h -1 to maintain the physiological requirement. All groups were given tracheotomy and mechanical ventilation, and the hemodynamic changes were monitored by pulse-indicated continuous cardiac output (PiCCO). The dynamic changes of hemodynamic indexes, arterial blood gas analysis, electrolytes, blood glucose and renal function biomarkers were monitored before modeling, immediately after modeling and 3, 6, and 12 hours after resuscitation. Results:① Hemodynamic indicators: after modeling, the MAP in the model group and the four fluid resuscitation groups decreased significantly, the cardiac index (CI) increased, and the systemic vascular resistance index (SVRI), global end-diastolic volumn index (GEDVI) decreased. After different crystalloid resuscitation at different time points, MAP, SVRI, and GEDVI increased in the four crystalloid groups. ②Arterial blood gas analysis, electrolytes, blood glucose: blood lactic acid (Lac) in the model group and the four fluid resuscitation groups increased after model success. After fluid resuscitation, the Lac of each crystalloid group began to decrease and reached to the lowest at 12 hours. Compared with the LR, AR and SPMCG groups, the pH value decreased in the NS group at 6 hours and 12 hours of fluid resuscitation (6 hours: 7.29±0.00 vs. 7.40±0.02, 7.35±0.02, 7.37±0.02; 12 hours: 7.27±0.02 vs. 7.38±0.02, 7.39±0.02, 7.35±0.01; all P < 0.05). After fluid resuscitation, blood Cl - levels at 3, 6, and 12 hours in the NS group were significantly higher than those in the LR, AR and SPMCG groups (mmol/L: 113.4±0.6 vs. 101.4±3.6, 108.0±1.1, 106.0±0.8 at 3 hours; 115.1±2.0 vs. 101.1±2.7, 109.0±2.2, 105.3±0.6 at 6 hours; 116.9±0.1 vs. 104.2±4.4, 107.6±1.7, 108.7±0.6 at 12 hours; all P < 0.05). There was no significant difference in blood glucose at each time point among the four crystalloid groups. ③ Biomarkers of renal function: blood and urine neutrophil gelatinase associated lipocalin (NGAL) and cystatin C (Cys C) were significantly increased in the model group and four fluid resuscitation groups. After fluid resuscitation, blood, urine NGAL and Cys C decreased. There was no significant difference in blood, urine NGAL and Cys C at all the time points among the different fluid resuscitation groups. Conclusions:In the rabbit model of septic shock induced by Escherichia coli LPS, hyperchloremia and acidosis occurred after NS resucitation, but did not occur during the recovery of LR, AR and SPMCG. There was no difference in the effects of different crystalloid resuscitation on renal function in septic shock rabbits.

The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3β, a key regulatory kinase in the Wnt pathway, regulates the ability of β-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3β activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3β, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS.

Objective:To investigate the application value of Clavien-Dindo classification in evaluation of postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Methods:The retrospective cohort study was conducted. The clinicopathological data of 262 patients with gastric cancer who were admitted to the 940th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army from January 2016 to January 2019 were collected. There were 214 males and 48 females, aged (58±11) years, with a range from 17 to 81 years. Of 262 patients, 120 cases undergoing Da Vinci robotic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into robotic group, and 142 cases undergoing laparoscopic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into laparoscopic group. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3)complications; (4) stratified analysis; (5) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect complications, tumor recurrence and survival of patients within postoperative 2 months. The follow-up was up to May 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data between groups was analyzed using the rank sum test. Results:(1) Intraoperative and postoperative situations: cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, the number of lymph node dissected, time to first flatus, time to initial fluid diet intake, duration of postoperative hospital stay of the robotic group were 1, (243±42)minutes, 100 mL(range, 100-150 mL), 38±15, (2.8±1.0)days, 3 days(range, 3-4 days), 11 days(range, 9-13 days), respectively. The above indicators of the laparoscopic group were 2, (244±38)minutes, 100 mL(range, 100-150 mL), 34±14, (3.2±1.0)days, 4 days(range, 3-5 days), 10 days(range, 9-13 days), respectively. There were significant differences in the number of lymph node dissected, time to first flatus, time to initial fluid diet intake between the two groups ( t=2.068, -3.030, Z=-3.370, P<0.05), and there was no significant difference in cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay between the two groups ( χ2=0.000, t=-0.158, Z=-1.824, -0.088, P>0.05). (2) Postoperative pathological examination: cases with well differentiated tumor, moderately differentiated tumor, poorly differentiated tumor, signet ring cell carcinoma or other types of tumor, cases in stage T1b, T2, T3 or T4a (pT staging), cases in stage N0, N1, N2, N3a or N3b (pN staging), cases in stage ⅠB, ⅡA, ⅡB, ⅢA, ⅢB or ⅢC (pTNM staging) of the robotic group were 6, 50, 55, 9, 10, 22, 63, 25, 42, 19, 19, 24, 16, 17, 22, 23, 20, 23, 15, respectively. The above indicators of the laparoscopic group were 4, 42, 84, 12, 6, 18, 81, 37, 39, 27, 32, 19, 25, 13, 19, 28, 39, 16, 27, respectively. There was no significant difference in the above indicators between the two groups ( Z=-1.880, -1.827, -0.140, -1.460, P>0.05). (3) Complications: cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death, cases with overall complications, cases with severe complications of the robotic group were 9, 6, 3, 2, 2, 0, 0, 22, 7, respectively. The above indicators of the laparoscopic group were 12, 15, 9, 6, 3, 1, 1, 47, 20, respectively. There were significant differences in cases with overall complications, cases with severe complications between the two groups ( χ2=7.309, 4.790, P<0.05), and there was no significant difference in cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death between the two groups ( χ2=0.080, 2.730, 1.042, 0.704, 0.000, 0.000, 0.000, P>0.05). (4) Stratified analysis: of the patients with overall complications in robotic group, cases of male or female, cases aged ≥65 years or <65 years, cases with body mass index (BMI) ≥24 kg/m 2 or <24 kg/m 2, cases with tumor diameter ≥5 cm or <5 cm, cases with or without abdominal surgery, cases with tumor located at upper stomach or middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of American Society of Anesthesiologists (ASA) classification, cases with well differentiated tumor or undifferentiated tumor, cases in stage Ⅰ-Ⅱ or stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes or <250 minutes, cases with volume of intraoperative blood loss ≥150 mL or <150 mL, cases with the number of lymph node dissected ≥25 or <25 were 15, 7, 14, 8, 11, 11, 16, 6, 4, 18, 19, 3, 15, 7, 7, 15, 8, 14, 12, 10, 12, 10, 14, 8, respectively. The above indicators of patients with overall complications in the laparoscopic group were 33, 14, 17, 30, 16, 31, 36, 11, 11, 36, 27, 20, 31, 16, 13, 34, 14, 33, 24, 23, respectively. Of the patients with overall complication, there were significant differences in cases of male, cases aged ≥65 years or <65 years, cases with BMI<24 kg/m 2, cases with tumor diameter≥5 cm, cases without abdominal surgery, cases with tumor located at middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of ASA classification, cases with well differentiated tumor, cases in stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes, cases with volume of intraoperative blood loss <150 mL, cases with the number of lymph node dissected ≥25 between the two groups ( χ2=6.683, 4.207, 6.761, 7.438, 4.297, 6.325, 9.433, 3.970, 4.850, 4.911, 3.952, 3.915, 6.865, 4.128, P<0.05) and there was no significant difference in cases of female, cases with BMI≥24 kg/m 2, cases with tumor diameter <5 cm, cases with abdominal surgery, cases with tumor located at upper stomach, cases with undifferentiated tumor, cases in stage Ⅰ-Ⅱ (pTNM staging), cases with operation time < 250 minutes, cases with volume of intraoperative blood loss ≥150 mL, cases with the number of lymph node dissected <25 between the two groups ( χ2=0.277, 1.052, 1.996, 1.552, 2.172, 2.594, 2.244, 3.771, 1.627, 3.223, P>0.05). (5) Follow-up: 262 patients were followed up postoperatively for 2 months. During the follow-up, no patient was diagnosed with tumor recurrence, and one patient in the laparoscopic group died of severe infection. Conclusions:The Clavien-Dindo classification can be used in evaluating postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Compared with laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy, Da Vinci robotic-assisted total gastrectomy with D 2 lymphadenectomy has the advantages of minimally invasiveness, low incidence of overall and severe complication.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Objective:s To evaluate the impacts of prior surgical scores(PSS) on the clinical efficacy and perioperative safety of cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) for pseudomyxoma peritonei(PMP).Methods:From the comprehensive PMP database, we collect the cases treated for the first time by CRS+ HIPEC, to form this study cohort. The clinicopathological features, PSS, CRS+ HIPEC details, overall survival(OS), and serious adverse events(SAEs) are systematically analyzed, to study the correlations between PSS and OS or SAEs.Results:335 PMP cases received standardized CRS+ HIPEC in this study. The median OS is 58.2 months for PSS-0 patients, 63.7 months for PSS-1, and 55.4 months for PSS-2/3, with no statistically significant differences in OS among the different PSS groups(χ 2=0.499, P=0.779). Subgroup analysis by pathologic types also found no statistically significant differences among the different PSS groups. Moreover, no significantly statistical differences are observed in overall SAEs(χ 2=0.625, P=0.722), CRS-related SAEs(χ 2=0.267, P=0.901), and non-CRS-related SAEs(χ 2=0.677, P=0.715), among the different PSS groups. Conclusions:PSS does not pose significant impacts on the efficacy and safety of CRS+ HIPEC for PMP patients at experienced treatment center.

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Objective: To construct and implement a calculation model of clinical nursing post classification. Methods: Between October to December 2018, head nurses of the hospital were screened as consultants, and Delphi method was used to determine the indicators, while the weights were assigned from the aspects of nursing workload, work quality, patient satisfaction and number of nursing night shifts. Combined with HIS data, the calculation model of clinical nursing post classification was constructed to classify clinical nursing units into different categories and levels. Results: After two rounds of expert enquiry, 82 nursing work items were identified and the objective weight assignment was determined ranging from 0.80 to16.14. According to the established calculation model and HIS data, nursing posts in clinical departments were classified into 6 levels and 3 categories, and the accurate management of clinical nursing post classification was achieved. Conclusions The construction of a calculation model is scientific and rigorous, which provides a scientific basis for dynamic nurse performance management and rational allocation of human resources. In addition, it provides a useful reference for accurate nursing management.