[The similar characteristics of IgG4-related disease and allergic diseases].

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.

[Risk factors of systemic allergic reactions caused by subcutaneous allergen immunotherapy].

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.

[Progress on the diagnosis and therapy about atopic diseases and primary immunodeficiency diseases].

Primary immunodeficiency diseases (PID) is a congenital disease caused by single gene germline mutation related to the immune system. PID patients have immune dysregulation, and are susceptible to infectious diseases, autoimmune diseases, autoimmune diseases, allergic diseases, and malignant tumors. The first symptom of some PID patients is atopic disease, therefore they go to the department of allergy, department of pediatrics and other relevant departments. How to identify and diagnose PID in allergic patients, to reduce diagnosis delay and prevent disease aggravation are the abilities that allergists, pediatricians, and doctors in other relevant departments need to master. This article summarizes the warning signs of PID in allergic patients and the mechanism of allergy combined with PID, and then summarizes the common types of PID in allergic patients, the evaluation, treatment and prevention in patients with PID and allergy.

[The characteristics and change of aeroallergens in children from 2015 to 2020 in a hospital of pediatric in Beijing].

Objective: To analyze the characteristics of clinical distribution and change of aeroallergens in children with allergic diseases from 2015 to 2020. Methods: Children who visited Capital Institute of Pediatrics affiliated Children's Hospital, suspected of allergic diseases and received serum aeroallergens specific immunoglobulin E (sIgE) test were retrospectively enrolled (1 to 14 years old). sIgE was detected by Phadia1000 system with radioallergosorbent test fluorescent enzyme-linked immunoassay. The characteristics and change of the aeroallergens among the 6 years was analyzed. Enumeration data were expressed by percentage and categorical variables were compared by the independent samples t-test and Pearson χ2 test. Results: In total 4 608 tests (4 575 patients) of children were enrolled, the average age was (5.4±2.9) years old, with the median age of 5.0 years old. 3 176 were boys (68.9%), and 1 432 were girls (31.1%). 4 294 children were from the north of China (93.2%), 295 children were from the south of China (6.4%), and 19 children were from unknown regions (0.4%). In total the most common aeroallergen was mold mixture (1 956/4 457 tests, 43.9%) and Alternaria alternata (276/630 tests, 43.8%), followed by Artemisia (300/889 tests, 33.7%), Humulus scandens (12/38 tests, 31.6%) and grass mixture (909/2 874 tests, 31.6%). Among the 6 years, mold, grass pollen and tree pollen sensitization increased, and mold [38/130 (29.2%) vs 1 574/3 233 (48.7%)], grass pollen [11/77 (14.3%) vs 1 069/3 072 (34.8%)] increased significantly (χ2 was 18.953 and 49.559, respectively, P=0.000). Positive rate of tree pollen increased [1/10 (10.0%) vs 516/2 122 (24.3%)], but did not have statistical significance (χ²=1.111, P=0.292). Dust mite [36/146 (24.7%) vs 321/1 408 (22.8%)] and hair of pets [7/33 (21.2%) vs 321/1 408 (17.1%)] sensitization didn't change greatly (χ2 =0.258, P =0.611; χ2 =0.379, P =0.538). In 2015, the most common aeroallergens was mold (38/130, 29.2%), followed by dust mite (36/146, 24.7%), while in 2020, the most common aeroallergens was still mold (1 574/3 233, 48.7%), with grass pollen (1 069/3 072, 34.8%) and tree pollen (516/2 122, 24.3%) ranked after. Conclusion: Mold might be the most common aeroallergens in allergic children in Beijing area. With time went on, dust mite was gradually exceeded by grass pollen and tree pollen.

[Efficacy and safety of catheter-directed interventional therapy in patients with acute pulmonary embolism].

Objective: To evaluate the efficacy and safety of catheter-directed interventional therapy in patients with acute pulmonary embolism(PE). Methods: PE was diagnosed by CT pulmonary angiography(CTPA). After risk stratification, a total of 79 PE patients (age (58.9±14.9) years old)were treated with catheter-directed interventional therapy via pulmonary vessels. The changes of pulmonary hemodynamics were compared before and after treatment. The risk of complications and side effects were observed. Results: The pulmonary artery pressure was changed followed by interventional therapy. The interventional therapy significantly decreased mean pulmonary arterial pressure (mPAP) from (35.3±11.2)mmHg (1 mmHg=0.133 kPa) to (30.0±10.6)mmHg (t=8.803,P<0.05) and the echocardiographic derived right ventricular dimension to left ventricular dimension (RV/LV) ratio from 0.93±0.16 to 0.83±0.15 (t=6.868,P<0.05). The arterial partial pressure of oxygen was increased from (69.0±8.6)mmHg to (75.1±9.9)mmHg (t=8.561,P<0.05) . The oxygen saturation was also increased from (93.9±2.9)% to (95.1±1.9)% at 24 h after the treatment (t=2.621,P<0.05) . Patients were further grouped as high-risk group (n=28) and intermediate risk group (n=51). mPAP and RV/LV ratio were significantly reduced in the two subgroups (all P<0.05) and the range of reduction was more significant in the high-risk group. Five patients experienced minor bleeding complication, 3 patients suffered worsened dispone post procedure and were treated with mechanical ventilation, 1 patient died, and 1 patient developed recurrent PE. Conclusion: The catheter-directed interventional therapy improves pulmonary hemodynamics and reduces load of right ventricle both in high-risk or intermediate risk PE patients, this therapy strategy is safe and effective for patients with PE.

Acute acalculous cholecystitis in patients with systemic lupus erythematosus: A unique form of disease flare.

Objective We aimed to investigate the clinical features of acute acalculous cholecystitis (AAC) in patients with systemic lupus erythematosus (SLE). Methods SLE patients with AAC hospitalized in the Peking Union Medical College Hospital (PUMCH) from January 2001 to September 2015 were retrospectively analyzed. Their medical records were systematically reviewed. The diagnosis of AAC was based on clinical manifestations and confirmed by radiologic findings including a distended gallbladder with thickened wall, pericholecystic fluid and absence of gallstones. Results Among the 8411 hospitalized SLE patients in PUMCH, 13 (0.15%) were identified to have SLE-AAC. Eleven (84.6%) of them were female, with a mean age of 30.1 ± 8.6 years. AAC was the initial manifestation of SLE in four (30.8%) cases. Eleven (84.6%) patients complained of fever and abdominal pain, four (30.8%) had positive Murphy's sign and six (46.2%) had elevated liver enzymes. The median SLE Disease Activity Index was 8.0 (range 0-20.0) at the time of AAC. Other affected organs in SLE-AAC included kidney (11, 84.6%) and hematologic system (11, 84.6%), followed by mucocutaneous (seven, 53.8%), musculoskeletal (seven, 53.8%) and neuropsychiatric (two, 15.4%) systems. All patients received treatment of glucocorticoids and immunosuppressants but none underwent surgical intervention. During a median follow-up of 28 months (range, 2-320 months), 12 cases (92.4%) responded to treatment with no relapse and one patient (7.6%) died of septic shock. Conclusion Our study suggests that AAC is a relatively uncommon and underestimated gastrointestinal involvement of SLE that is often associated with active disease. For patients with AAC in SLE, treatment with aggressive glucocorticoids could result in a good prognosis.

[Effect of allogenic mesenchymal stem cells transplantation on the expression of interleukin-22 and matrix metalloproteinase-3 in rats with collagen induced arthritis].

Objective: To study the effect of allogeneic bone marrow mesenchymal stem cells transplantation on the expression of interleukin -22 (IL-22), matrix metalloproteinase -3 (MMP-3) in serum and synovial of rats with collagen induced arthritis. Methods: Type Ⅱ collagen were injected twice to establish the collagen induced arthritis (CIA) rat model. Forty-eight rats were randomly divided into 3 groups: control group, CIA control group, CIA experiment group. Rat bone marrow mesenchymal stem cells were cultured by bone marrow method combined with adherent culture method. After identify, the remaining cells were injected in the CIA experimental group. Enzyme linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of IL-22 and MMP-3 in serum and anklebone joint's synovium of rats, respectively. Synovial cells were isolated and cultured, and were treated with different concentrations of IL-22. MMP-3 protein and mRNA were detected before and after stimulation by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results: After MSC transplantation, arthritis index, X-ray, HE staining of CIA rat showed that joint damage significantly reduced compared with the control group. The ELISA results showed that the expression of MMP-3 and IL-22 in CIA control group was higher than those in the control group (125.79±9.12 vs 102.00±7.63 ng/ml, P<0.05), (292.35±31.23 vs 257.27±13.99 ng/ml, P<0.05) and CIA experiment group (125.79±9.12 vs 97.94±9.50 ng/ml, P<0.05), (292.35±31.23 vs 262.16±22.02 ng/ml, P<0.05) with statistically significant difference (P<0.05). There was no significant difference between the control group and CIA experimental group. Immunohistochemical showed similar results with ELISA. Western blotting and RT-qPCR showed that MMP-3 protein and mRNA expression was increased after IL-22 stimulation in a dose-dependent manner. Conclusion: IL-22 and MMP-3 play an important role in the pathogenesis of rheumatoid arthritis. IL-22 could regulate the expression of MMP-3, and bone marrow mesenchymal stem cells could reduce the expression of MMP-3 in the treatment of rheumatoid arthritis by reducing the expression of IL-22.

[The 452th case: rash, hypotension, abdominal pain and headache].

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized with multiple organ involvements. Acute acalculous cholecystitis(AAC) is an extremely rare manifestation of digestive system involvement in SLE. We reported a case of 32-year-old woman who complained skin rashes for two weeks and stomachache and oliguria for one day. She had rashes at onset, and developed fever, stomachache, hypotension and headache. Physical examination at admission indicated blood pressure 76/47 mmHg(1 mmHg=0.133 kPa), heart rate 107 beats/min, warm acra. Murphy's sign was positive. Ultrasound suggested the enlarged gallbladder with surrounding hypoecho band yet no biliary calculi were found. A diagnosis of SLE was made, characteristic with distributive shock at the onset and AAC, complicated with neuropsychiatric lupus and lupus nephritis. She had an acute and severe course of disease, which had been relieved after treatment of high dose glucocorticoid and immunosuppressants. This case arouses clinicians to pay more attention to AAC as a rare form of disease flare in SLE. Early diagnosis of AAC is crucial to a favorable prognosis and in avoid of abdominal surgery.

Diversity and evolution of Ty1-copia retroelements within Chalcidoidea by reverse transcriptase domain analysis.

Ty1-copia retrotransposons are widespread and diverse in insects. Some features of their hosts, such as mating and genetic systems, are predicted to influence the spread of selfish genetic elements like Ty1-copia. Using part of the reverse transcriptase gene as a reference, we experimentally surveyed Ty1-copia elements in eight species of fig wasps (Hymenoptera: Chalcidoidea), and performed an in silico analysis of six available genomes of chalcid wasps. Contrary to initial expectations that selfish elements such as Ty1-copia would be purged from the genomes of these species because of inbreeding and haplodiploidy, almost all of these wasps harbour an abundance of diverse Ty1-copia elements. Phylogenetic analyses suggest that the families of Ty1-copia elements found in these species have had a long association with their chalcid hosts. These results suggest an evolutionary scenario in which there was ancestral polymorphism followed by some taxa-specific events including stochastic loss and further diversification. Furthermore, estimating natural selection within the internal and terminal portions of the Ty1-copia phylogenies demonstrated that the elements are under strong evolutionary constraints for their long-term survival, but evolve like pseudogenes in the short term, accompanied by the rise and fall of parasitic elements in the history of wasp lineage.

Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer.

BACKGROUND: Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), which is identified as a novel intestinal stem cell marker, is overexpressed in various tumours. In this study, we explore Lgr5 expression in gastric carcinoma and analyse its role in invasion, metastasis, and prognosis in carcinoma. METHODS: A combination of immunohistochemistry, western blotting, and quantitative reverse transcription-polymerase chain reaction were used to detect mRNA and protein expression levels of Lgr5 and matrix metalloproteinase 2 (MMP2). Small interfering RNA against Lgr5 was designed, synthesised, and transfected into AGS cells. The effects of Lgr5 siRNA on cell invasion were detected by transwell invasion chamber assay and wound healing assay. RESULTS: Leucine-rich repeat-containing G-protein-coupled receptor 5 expression was significantly higher in gastric carcinomas than in normal mucosa. Leucine-rich repeat-containing G-protein-coupled receptor 5 expression positively correlated with the depth of invasion, lymph node metastasis, distance of metastasis, and MMP2 expression levels. Multivariate analysis showed that Lgr5 had an independent effect on survival, and that it positively correlated with MMP2. Leucine-rich repeat-containing G-protein-coupled receptor 5 siRNAs inhibited Lgr5 mRNA and protein expression. Transwell assays indicated that these siRNAs resulted in significantly fewer cells migrating through the polycarbonate membrane, and wound healing assay also indicated that siRNAs decreased the migration of cells. Inhibition of Lgr5 resulted in a significant decrease in MMP2 and ß-catenin levels compared with those in controls. CONCLUSIONS: Leucine-rich repeat-containing G-protein-coupled receptor 5 was correlated with invasion and metastasis. Leucine-rich repeat-containing G-protein-coupled receptor 5 inhibition could serve as a novel therapeutic approach.

Odorant-binding protein (OBP) genes affect host specificity in a fig-pollinator mutualistic system.

The interaction between figs and their pollinating wasps is regarded as a model system for studying specialized co-evolved mutualism. Chemoreception of fig wasps plays an important role in this interaction, and odorant-binding proteins (OBP) function in the first step of odorant detection. The OBP repertoire of the fig wasp Ceratosolen solmsi is reported to be one of the smallest among insects; however, it is unknown how these OBPs are related to the complicated mating process occurring within the fig cavity and the extreme host specificity of the species. In the present study, we combined a structural analysis of the conserved cysteine pattern and motif order, a phylogenetic analysis, and previous studies on ligand-binding assays to deduce the function of OBPs. We also quantified the expression of OBP genes in different life stages of female and male fig wasps by using real-time quantitative PCR, which can help to predict the function of these genes. The results indicated that CsolOBP1 and CsolOBP2 (or CsolOBP5) in males may bind to pheromones and play important roles in mate choice, whereas CsolOBP4 and CsolOBP5 may primarily function in host localization by females through binding of volatile compounds emitted by receptive figs.

Clinical effects and safety review of self-expanding stent surgery for extracranial carotid artery stenosis treatment.

This study aimed to investigate the clinical effects and safety review of self-expanding stent surgery in the treatment of extracranial carotid artery stenosis. Seventy-eight patients with carotid artery stenosis were applied with the self-expanding stent for endovascular interventional therapy. Eighty-one stents were implanted into 80 blood vessels of the 78 patients, in which protective umbrellas were used in 56 cases, and the success rate of stent implantation was 100%. The stenosis degree decreased from the preoperative (86.72 ± 9.5%) to the postoperative (13.43 ± 5.62%) stage, and the blood peak velocity of the stenosed vessels decreased from 189.58 ± 13.5 to 83.73 ± 5.61 cm/s. Transient blood pressure and heart rate decreases occurred in 21 cases, continuously low blood pressure and heart rate decreasing occurred in 29 cases, and acute occlusion of the ipsilateral middle cerebral artery occurred in 1 case, which was resolved through thrombolysis and thrombus breaking in time. Over-perfusion symptoms were observed in 13 cases, although without serious complications such as cerebral hemorrhage. The follow-up period continued for 6-32 months, and ultrasonography revealed that 77 cases had no stent-restenosis, while 1 case had restenosis. The application of self-expanding stents had good clinical effects, with fewer complications and higher safety for the treatment of extracranial carotid artery stenosis.

Incidence of acute mountain sickness in young adults at 3200 meters: comparison of the Lake Louise Scoring and Chinese Scoring Systems.

The purpose of this study was to compare two scoring systems used for the diagnosis of acute mountain sickness (AMS): the Lake Louise Scoring (AMS-LLS) and the Chinese Scoring Systems (AMS-CSS). In total, 339 healthy young adult volunteers residing at sea level ascended to 3200 m by train and bus over a total journey time of 48 h. All subjects ascended in the same manner and were divided into three groups that were assessed after one (N = 88), two (N = 91), and three (N = 160) nights, respectively, at altitude. The overall incidence of AMS was 17.11% (N = 58) and 29.79% (N = 101) according to the AMS-LLS and AMS-CSS, respectively. Two participants (0.59%) experienced high-altitude pulmonary edema. Both scoring systems showed the highest incidence of AMS after the second night at high altitude. The AMS-CSS and AMS-LLS scores were significantly correlated (Pearson's r = 0.820, P < 0.001). The AMS-CSS identified all AMS subjects diagnosed by the AMS-LLS, and an additional 43 subjects. The dominant symptoms were reduced exercise tolerance (61.7%), fatigue (49.0%), dizziness (28.9%), chest distress (28.3%), and headache (27.4%). Compared with the AMS-LLS, the sensitivity, specificity, and positive and negative predictive values of the AMS-CSS were 100, 84.7, 57.43, and 100%, respectively. There was no relationship between oxygen saturation levels and AMS scores at 3200 m. In summary, the AMS-CSS was similar to AMS-LLS, except that it resulted in more positive diagnoses, and headache did not play a large diagnostic role.

Addition of short-term androgen deprivation therapy to dose-escalated radiation therapy improves failure-free survival for select men with intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated (DE) radiation therapy (RT) and androgen deprivation therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa) is uncertain. PATIENTS AND METHODS: We identified 636 men treated for IR-PrCa with DE-RT (>75Gy). The adult comorbidity evaluation-27 index classifed comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. RESULTS: Forty-five percent received DE-RT and 55% DE-RT with ADT (median 6 months). On Cox proportional hazard regression that adjusted for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT classified Gleason 4 + 3 = 7 or ≥50% positive cores as unfavorable disease. The addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (P = 0.006) but did not improve FFS for men with unfavorable disease and moderate or severe comorbidity (P = 0.380). CONCLUSION: The addition of ADT to DE-RT improves FFS for men with unfavorable IR-PrCa, especially those with no or minimal comorbidity.

Theoretically exploring selective-binding mechanisms of BRD4 through integrative computational approaches.

The origin of cancer is related to the dysregulation of multiple signal pathways and of physiological processes. Bromodomain-containing protein 4 (BRD4) has become an attractive target for the development of anticancer and anti-inflammatory agents since it can epigenetically regulate the transcription of growth-promoting genes. The synthesized BRD4 inhibitors with new chemical structures can reduce the drug resistance, but their binding modes and the inhibitory mechanism remain unclear. Here, we initially constructed robust QSAR models based on 68 reported tetrahydropteridin analogues using topomer CoMFA and HQSAR. On the basis of QSAR results, we designed 16 novel tetrahydropteridin analogues with modified structures and carried out docking studies. Instead of significant hydrogen bondings with amino acid residue Asn140 as reported in previous research, the molecular docking modelling suggested a novel docking pose that involves the amino acid residues (Trp81, Pro82, Val87, Leu92, Leu94, Cys136, Asp144, and Ile146) at the active site of BRD4. The MD simulations, free energy calculations, and residual energy contributions all indicate that hydrophobic interactions are decisive factors affecting bindings between inhibitors and BRD4. The current study provides new insights that can aid the discovery of BRD4 inhibitors with enhanced anti-cancer ability.

[Surgical selection and metastatic warning of splenic lymph node dissection in advanced gastric cancer radical surgery: a prospective, single-center, randomized controlled trial].

Objective: To investigate the surgical options for splenic lymph node dissection in patients with advanced gastric cancer undergoing radical total gastrectomy, and to evaluate the sentinel effect of No. 4s lymph node on splenic lymph node metastasis. Methods: A prospective, single-center, randomized and controlled study was carried out (Trial registration, No.NCT02980861). Enrollment criteria: (1) >18 years old and <65 years old; (2) gastric adenocarcinoma locating in the proximal or corpus; (3) preoperative clinical staging as cT2-4aN0-3M0; (4) D2 radical total gastrectomy feasible judged before operation; (5) physical ability score 0 to 1; (6) I to III of ASA classification. Pregnant or lactating women, patients with severe mental illness or previous history of upper abdominal surgery, those suffered from other malignant tumors in the past 5 years, or heart and lung system diseases judged to affect surgery before operation, those receiving preoperative chemotherapy, radiotherapy or targeted therapies, and distant metastases being found during surgery were excluded. According to above criteria, 222 patients at The First Medical Center of Chinese PLA General Hospital from December 2016 to December 2017 were enrolled prospectively and were randomly divided into the laparoscopic splenic hilar lymph node dissection group (laparoscopic group, n=114) and the open splenic hilar lymph node dissection group (open group, n=108). The result of rapid frozen immunohistochemistry of harvested No.4s lymph nodes was used to evaluate the sensitivity and specificity of sentinel effect on splenic hilar lymph node metastasis. The surgical parameters, postoperative recovery parameters, and complication rates were compared between the two groups. Results: There were 80 males and 34 females in the lapascopic group with a mean age of (56.1±10.2) years, and 69 males and 39 females in the open group with a mean age of (58.4±10.9) years. There were no significant differences in baseline data between the two groups (all P>0.05). Total blood loss was less in the laparoscopic group [(96.3±82.4) ml vs. (116.6±101.9) ml, t=1.124, P<0.001], and the amount of bleeding from the splenic hilar lymph nodes dissected was also less than that in the open group [(25.3±17.8) ml vs. (59.5±36.4) ml, t=1.172, P<0.001]. However, the operation time, the time of splenic hilar lymph node, the number of lymph node dissected and number of splenic hilar lymph node dissected were not significantly different between the two groups (all P>0.05). As compared to the open group, the laparoscopic group had shorter time to the first flatus [(1.3±1.2) days vs. (1.6±1.5) days, t=1.665, P=0.021], shorter time to fluid diet [(4.6±1.4) days vs. (4.9 ± 1.6) days, t=1.436, P=0.007], shorter time to remove nasogastric tube [(3.9±2.6) days vs. (4.3±2.4) days, t=0.687, P<0.001] and shorter hospital stay [(10.3±6.6) days vs. (12.1±7.2) days, t=0.697, P<0.001]. Complication rate was 14.0% (16/114) and (12.0%) ((1)3/108) in the laparoscopic group and the open group, respectively, without significant difference (χ(2)=6.723, P=0.331). The sensitivity of the No. 4s lymph node for the prediction of splenic hilar lymph node metastasis reached 89.5%, and the specificity reached 99.6%. Conclusions: Laparoscopic technique is safe and feasible in the treatment of splenic hilar lymph node dissection in advanced gastric cancer. The No.4s lymph node examination has good sentinel effect on predicting the metastasis of splenic hilar lymph nodes.

[Method of dietary nutritional status assessment and its application in cohort study of nutritional epidemiology].

Minimizing the burden on study subjects and assessing the general dietary nutritional status as accurately as possible are the basis of a nutritional epidemiological cohort study in the general population. While introducing the main dietary nutrition assessment methods, this paper manly describes the basic contents and principles for the development of food frequency questionnaire, and briefly illustrates the problems and solutions for the development of area specific food frequency questionnaires by taking the example of Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study. Finally, discusses preliminarily the necessity and possibility of developing a national food frequency questionnaire.

Observation of efficacy of TACE combined with HIFU on patients with middle-advanced liver cancer.

OBJECTIVE: To study the efficacy of transarterial chemoembolization (TACE) combined with high-intensity focused ultrasound (HIFU) in patients with middle-advanced liver cancer. PATIENTS AND METHODS: A total of 100 patients with middle-advanced liver cancer treated in our hospital from January 2015 to January 2018 were selected and randomly divided into TACE group (control group, n=50) and TACE combined with HIFU group (experimental group, n=50) according to different therapeutic regimens. The efficacy was observed after the operation, the blood was collected to detect the postoperative liver function indexes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the postoperative complications were observed. Also, the immune indexes cluster of differentiation 3+ (CD3+), CD4+, and CD8+ were determined. Moreover, the quality of life (QOL) score was compared between the two groups, the 1-, 2-, 3-, and 5-year survival rates were observed after the operation. Also, the changes in the levels of tumor markers α-L-fucosidase (AFU), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were observed. RESULTS: In experimental group, the levels of AST, ALT, and blood urea nitrogen (BUN) after the operation were significantly decreased (p<0.05), while the postoperative efficacy was significantly superior to that in control group (p<0.05). The incidence of postoperative complications was significantly reduced (p<0.05), the levels of CD3+, CD4+, CD8+, and natural killer (NK) cells were markedly increased (p<0.05). Also, the QOL score was evidently better than that in control group (p<0.05) and the 1-, 2-, 3-, and 5- year survival rates after the operation were evidently higher than those in control group (p<0.05). After treatment, the levels of AFU, AFP, CA19-9, and CEA were remarkably lower than those before treatment in both groups, while they were remarkably lower in experimental group than those in control group (p<0.05). CONCLUSIONS: TACE combined with HIFU in the treatment of patients with middle-advanced liver cancer can restore the hepatic metabolism, enhance the immunity, improve the QOL, prolong the survival time of patients, and significantly reduce the tumor markers. Also, it has fewer adverse reactions and definite overall efficacy, which is worthy of popularization and application.

Cocaine increases endoplasmic reticulum stress protein expression in striatal neurons.

Cocaine administration upregulates the levels of extracellular glutamate and dopamine in the striatum. Activation of the receptors alters calcium homeostasis in striatal neurons leading to the expression of the endoplasmic reticulum (ER) stress proteins. It was therefore hypothesized that cocaine upregulates the expression of the ER stress proteins, immunoglobulin heavy chain binding protein (BiP), Ire1alpha and perk via glutamate and dopamine receptor activation. A novel glutamate microbiosensor and Western immunoblot analyses were mainly performed to test the hypothesis in the rat dorsal striatum. The results showed that i.p. injection of repeated cocaine (20 mg/kg) for nine consecutive days significantly increased extracellular glutamate levels while acute cocaine injection did not. However, the immunoreactivities (IR) of the ER stress proteins in the dorsal striatum were significantly increased by either acute or repeated cocaine injections as compared with saline controls. Intrastriatal injection (i.s.) of the selective group I metabotropic glutamate receptor (mGluR) antagonist N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC; 25 nmol) or the mGluR5 subtype antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP; 2 and 25 nmol) significantly decreased repeated cocaine-induced increases in the IR of the ER stress proteins in the injected dorsal striatum. Similarly, the selective D1 antagonist (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0.1 mg/kg, i.p.) or the N-methyl-d-aspartate antagonist dizocilpine/(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-ibenzo[a,d]cyclohepten-5,10-imine maleate (MK801; 2 nmol, i.s.) decreased acute or repeated cocaine-induced the IR of the ER stress proteins in the dorsal striatum. These data suggest that cocaine upregulates expression of the ER stress proteins in striatal neurons via a mechanism involving activation of glutamate and dopamine receptors.

Dose de-escalation to adalimumab 40 mg every 3 weeks in patients with Crohn's disease - a nested case-control study.

BACKGROUND: Data on dose de-escalation in patients with Crohn's disease (CD) are limited. AIM: To evaluate outcomes of dose de-escalation from adalimumab (ADM) every other week (EOW) to every three weeks (ETW). METHODS: We selected patients with CD receiving maintenance therapy with ADM 40 mg ETW with serum levels (SL) available before and after dose de-escalation. Sex- and age-matched controls continuing ADM 40 mg EOW were identified. Patient reported outcome, C-reactive protein (CRP) and serum albumin were collected. RESULTS: Out of 898 patients, we identified 40 (11 male, median 37 years) who de-escalated to ADM 40 mg ETW for ADM-related adverse events (AE, n = 1), ADM SL >7 µg/mL (n = 8), or both (n = 31). Compared to controls, ADM SL dropped significantly within 4 months, without associated clinical or biochemical changes. In 53% of patients, dose de-escalation was associated with disappearance of AE (8/16 skin manifestation, 3/6 arthralgia, 5/7 frequent infectious episodes). During a median follow-up of 24 months, 65% of patients maintained clinical response, but 35% needed dose escalation back to ADM 40 mg EOW because of clinical relapse (n = 8), ADM SL <4 µg/mL (n = 2), or both (n = 4). CRP <3.5 mg/L at dose de-escalation was independently associated with dose escalation-free survival [odds ratio 6.28 (95% CI 1.83-21.59), P = 0.004]. We could not define a minimal ADM SL to consider or maintain dose de-escalation. CONCLUSIONS: Overall, 65% of patients who de-escalated to adalimumab 40 mg every 3 weeks remained in clinical remission for a median of 24 months. In 53% of patients, adalimumab-related adverse events disappeared after dose de-escalation. Regardless of adalimumab SL, disease remission should be assessed objectively prior to dose de-escalation.