[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.

[Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma].

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

[Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years].

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

[Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma].

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

[Intervention effects of drugs on GSH and SOD enzyme activity of rats kidney acutely poisoned by nickel carbonyl].

Objective: To evaluate the intervention effect of various drugs on glutathione (GSH) and superoxide dismutase (SOD) enzyme activity of rats kidney with acute nickel carbonyl poisoning. Methods: In January 2019, The 250 SPF male SD rats were randomly divided into normal control group (n=10) , poisoned group (n=40) and treatment groups (n=200) according to the random number table method. And the treatment groups were divided into methylprednisolone group (20 mg/kg) , DDC group (100 mg/kg) , sodium selenite group (10 µmol/kg) , Shenfu huiyang decoction group (0.25 ml) and methylprednisolone combined with DDC group (100 mg/kg) , with 40 mice in each group. Except for the normal control group, rats in the other groups were exposed to nickel carbonyl for 30 min, at 4 h and 30 h after exposure, the rats in each treatment group were intraperitoneally injected with corresponding drugs, and kidney tissues were collected 3 d and 7 d after administration, with 10 mice in each group. The activities of GSH and SOD in kidney were measured by enzyme-linked immunosorbent assay, and using electron microscopy observe ultrastructure changes. Results: Compared to the control group, the activities of GSH and SOD enzyme of poisoned group were significantly decreased at 3 d or 7 d after 4 h or 30 h exposure, and the difference was statistically significant (P=0.000, 0.031, 0.001, 0.033) , the epithelial nuclei of proximal convoluted tubules were pyknosis and lysosome hyperplasia in the cytoplasm. And compared to poisoned group, the activities of GSH and SOD enzyme of methylprednisolone+DDC group were significantly increased at treatment with 7 d after 4 h exposure, the difference was statistically significant (P=0.022, 0.000) , and the activities of GSH and SOD enzyme of methylprednisolone and enzyme of methylprednisolone+DDC group were significantly higher at 7 days than at 3 days, the difference was statistically significant (P=0.020, 0.017, 0.018, 0.033) . The results of electron microscopy showed that the cell nuclei and cytoplasmic organelles of proximal convolute tubule were almost restored to normal tissue level of both methylprednisolone group and methylprednisolone+DDC group. Conclusion: The methylprednisolone and methylprednisolone+DDC have obvious repair effect on renal enzyme activity level of rats with acute nickel carbonyl poisoning, and the treatment effect is better for a long time of medication.

Endovascular treatment of visceral aneurysms and pseudoaneurysms.

Visceral artery aneurysm (VAA) is a rare and potentially life-threatening condition, defined as true artery aneurysms and pseudoaneurysms of splanchnic circulation and renal artery. This study reports our experience in the diagnosis and endovascular treatment of visceral artery aneurysms (VAAs) over a 10-year period. Between 2008 and 2018, a total of 24 VAAs in 21 patients were diagnosed by clinical symptoms and a combination of imaging techniques, such as Doppler ultrasound, computed tomography angiogram, and catheter angiogram. All patients underwent endovascular treatment to exclude aneurysms. Oral antiplatelet medicine was administered, and imaging examination was performed during follow-up. Technical success was achieved in all 21 patients, and no periprocedural complications occurred. Endovascular coiling alone was employed in 10 aneurysms. Coiling was combined with gelfoam in 2 aneurysms. Coiling was assisted by stent in 4 aneurysms. Covered stents were deployed in 8 aneurysms individually. Clinical symptoms disappeared or highly improved in all patients after treatment. None of the patients showed recurrent symptoms after discharge. However, two cases with new aneurysms after 6 and 8 months, respectively, and one case with in-stent thrombosis after 12 months were reported during follow-up. This study may justify the efficacy of percutaneous endovascular coil embolization and stent deployment. It also provides beneficial experience about how to choose appropriate various endovascular strategies based on both clinical symptoms and aneurysm anatomy condition.

Identifying optimal virtual water management strategy for Kazakhstan: A factorial ecologically-extended input-output model.

Virtual water is an important indicator measuring the amount of water needed from the perspective of consumption, which can help decision makers to identify desired system design and optimal management strategy against water resources shortage. In this study, a novel model named as factorial ecologically-extended input-output model (abbreviated as FEIOM) is developed for virtual water management. FEIOM integrates techniques of input-output model (IOM), ecological network analysis (ENA) and factorial analysis (FA) into a general framework. It is effective to evaluate the virtual water flows, reveal ecological inter-connections in virtual water system (VWS), and identify key water consumption sectors that have significant individual and interactive effects on VWS's performance. FEIOM is then applied to identifying optimal virtual water management strategies for Kazakhstan in Central Asia. The main findings are: (i) Kazakhstan is a net importer of virtual water (reaching up to 46.0 × 109 m3), demonstrating that the national economic structure is reasonable, which can abate the national water scarcity and improve its eco-environmental protection; (ii) the virtual water of agricultural sector is net exporter, where vegetables, fruits and nuts occupy 86% of the total agricultural exports; the massive export of water-intensive products further squeezes the water for other users; (iii) the key factors affecting the national VWS are agriculture > primary manufacturing > advanced manufacturing > services. Therefore, from solving water resources shortage and facilitating sustainable development perspectives, Kazakhstan should stimulate the domestic primary manufacturing productions and improve agriculture and advanced manufacturing water-use efficiencies.

[Risk factors of peritoneal metastasis in primary appendiceal tumor].

Objective: To investigate the risk factors of peritoneal metastasis in primary appendiceal tumor. Methods: The clinic data of 71 patients with primary appendiceal tumor admitted in the Sixth Affiliated Hospital of Sun Yat-sen University between Dec 2012 and Jan 2019 were enrolled retrospectively. Multivariate logistic regression analysis were carried out to evaluate the risk factors of appendiceal tumor with peritoneal metastasis. Results: Of the 71 patients, 33 were peritoneal metastasis (peritoneal metastasis group) and 38 were non-peritoneal metastasis (no peritoneal metastasis group). Twenty-one patients in the peritoneal metastasis group had increased preoperative cancer embryo antigen (CEA), while 3 cases in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Sixteen cases in peritoneal metastasis group had increased preoperative carbohydrate antigen 199, while only 2 cases in the non-peritoneal metastasis group, the difference was statistically significant (P<0.001). The pathological type of 30 cases in the peritoneal metastasis group was adenocarcinoma (including mucus adenocarcinoma and colon adenocarcinoma), while 12 cases of adenocarcinoma in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Twelve cases in the peritoneal metastasis group had lymph node metastasis, while 3 cases in the non-peritoneal metastasis group, the difference is statistically significant (P=0.003). Preoperative CEA elevation and pathological type is adenocarinoma were independent risk factors for peritoneal metastasis of appendiceal cancer (P<0.05). Conclusions: The propensity of peritoneal metastasis in primary appendiceal tumor is high and the outcome is poor. Patients with increased preoperative CEA, adenocarcinoma histopathology are more inclined to have peritoneal metastasis.

[Etiology of severe community-acquired pneumonia in immunocompromised patients].

Objective: To analyze the etiology of severe community-acquired pneumonia (SCAP) in immunocompromised patients, and to investigate the relationship between underlying diseases and infectious microorganisms. Methods: A retrospective analysis was performed on SCAP in immunocompromised patients admitted to the Fourth Department of Respiratory and Critical Medicine (MICU) of China-Japan Friendship Hospital from January 1, 2017 to December 31, 2019. A total of 119 SCAP patients were finally enrolled, including 65 males (54.6%), with an average age of (59.3±14.5) years. The average of Sequential Organ Failure Assessment (SOFA) score was 6.7±3.6 and the acute physiology and chronic health evaluation (APACHE) Ⅱ score was 19.4±6.8. Sixty (50%) of these patients were finally improved and discharged. Long-term glucocorticoid treatment was the main risk factor for immunocompromise. The difference of pathogenic microorganisms between patients with and without structural lung diseases, and the influence of different pathogenic microorganisms on hospital mortality were calculated, respectively. P<0.05 was considered to be statistically significant. Results: In this study, 99 (83.2%) patients were identified to have positive etiological results, and the incidence of concurrent infection was 54.5%. The top three pathogens were Pneumocystis Jiroveci (55.6%), Cytomegalovirus (47.5%) and Aspergillus (23.2%). Staphylococcus aureus was the most common bacterium, followed by Pseudomonas aeruginosa and Klebsiella pneumoniae. The risk of Pneumocystis Jiroveci infection was significantly higher in patients without underlying lung diseases as compared to those with underlying lung diseases (64.3% vs. 44.2%, P = 0.046). The in-hospital mortality was not different among patients infected with different pathogens(all P>0.05), but was higher in those with mixed infections(56.7% vs. 33.9%, P=0.013). Conclusions: Pneumocystis Jiroveci and Cytomegalovirus were the most common pathogens in immunocompromised patients with severe community-acquired pneumonia, and the incidence of Pneumocystis Jiroveci was significantly higher in patients without underlying lung diseases.

[Application of artificial intelligence in prevention and control of COVID-19 in Guangzhou city].

Since the outbreak of COVID-19, it has spread rapidly throughout the country and even in the world. As a first tier city, Guangzhou is also the South Gate of China, with large population mobility and severe and complex prevention and control situation. Guangzhou CDC, together with Tencent and Alibaba Cloud, has made full use of its artificial intelligence technology to carry out a series of practices in case transmission chain analysis, close contact and other key personnel management, front-line staff prevention and control skills training and convenience services. Through the application of artificial intelligence in different scenarios, the difficulties and challenges in the prevention and control are solved, and the speed of epidemic prevention and control is increased.

[The prognostic value of circulating microRNA-29b in left ventricular hypertrophy in patients with hypertension].

Objective: To analyze the relationship between the level of microRNA-29b in circulation and left ventricular hypertrophy in hypertensive patients. Methods: A total of 240 subjects from Henan Province People's Hospital from June 2015 to June 2018 were included in the present study. Among them, 160 were hospitalized patients, and were divided into two groups. Patients with simple hypertension and had no left ventricular hypertrophy (80 cases) were in the simple hypertension group (HBP-NLVH), and patients with hypertension combined with left ventricular hypertrophy (80 cases) were in the high blood pressure with left ventricular hypertrophy group (HBP-LVH). Normal control subjects (80 cases) were those with no hypertension and randomly selected from the medical center of Henan Province People's Hospital. Serum microRNA-29b expressions were detected by real time fluorescence quantitative PCR. The thickness of interventricular septum (IVSD) and left ventricular posterior wall thickness (LVPWD) were measured by echocardiography. Results: Compared with the normal control group (1.95±0.79), the relative expression of microRNA-29b in the patients both in the HBP-NLVH group (2.67±0.92) and the HBP-LVH group (5.12±1.23) was up-regulated, and the difference between normal control and patients was statistically significant (P<0.05). In patients, the microRNA-29b level in the HBP-LVH group was significantly higher than that in the HBP-NLVH group (P<0.05). The expression level of microRNA-29b was positively correlated with IVSD (r=0.71, P<0.05) and LVPWD (r=0.74, P<0.05), respectively. The sensitivity and specificity of serum microRNA-29b levels in the diagnosis of left ventricular hypertrophy in hypertension patients were 96.8% and 91.3%, respectively. Conclusion: Serum microRNA-29b level is elevated in hypertensive patients with left ventricular hypertrophy, and is positively correlated with left ventricular hypertrophy. The circulation microRNA-29b might be a useful biomarker with prognostic value in left ventricular hypertrophy in hypertension patients.

[Clinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation].

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION: EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.

[Association between Lipoprotein(a) and the characteristics of left main coronary artery plaque in patients with stable angina pectoris].

Objective: To investigate the relationship between Lipoprotein (LP) (a) level and the characteristics of tissue components of left main coronary artery (LMCA) plaque. Methods: A total of 102 patients with stable angina pectoris who underwent percutaneous coronary intervention (PCI) in the People's Hospital of Henan Province from June 2010 to October 2016 were included. We performed intravascular ultrasound-virtual histology (IVUS-VH) to their LMCAs and evaluated the tissue characteristics, and the blood level of total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), ApoB, ApoA1, LP(a) were measured. According to the value of their LP(a) level they were divided into 2 groups (high LP(a) group (>300 mg/L) (n=35) and low LP(a) group (≤300 mg/L) (n=67)), then the relationship between the above lipid values and the tissue characteristics of the LMCA plaque in the patients were evaluated. Results: Patients with a high LP(a) had a larger percentage of fibrolipid volume and a smaller percentage fibrous volume compared to patients with a normal LP(a) (25%±5% vs 13%±6%, P<0.01 and 50%±8% vs 61%±9%, P<0.01). Using multivariate linear regression analysis after adjustment for the above-mentioned confounding factors, LP(a) had a significantly positive correlation with fibrolipid volume percentage (r=0.645, ß=0.29, P<0.01), and had a negative correlation with fibrous volume percentage (r=-0.467, ß=-0.32,P<0.01), suggesting that the LP(a) was associated with the vulnerability of the LMCA plaque. Conclusion: For the patients with stable angina pectoris, the LP(a) has a significantly positive correlation with the percentage of fibrolipid volume and a negative correlation with the percentage of fibrous volume, suggesting that the LP(a) could predict the vulnerability of the LMCA plaque.

[Characteristics of exercise ventilation and gas exchange in obese and extremely obese patients].

Objective: To evaluate the characteristics of exercise ventilation and gas exchange in obese and extremely obese patients by Cardiopulmonary exercise test (CPX). Methods: Restrospective anal-ysis of subjects who underwent CPET in Shengjing Hospital of China Medical University from June 2014 to June 2017. A total of 74 subjects were enrolled. According to the body mass index (BMI), 74 subjects were divided into control group(18.5 kg/m(2)≤BMI<23.9 kg/m(2)) (n=21), obese group (28.0 kg/m(2)≤BMI<40.0 kg/m(2)) (n=30) and extremely obese group(BMI≥40.0 kg/m(2))(n=23), respectively. V(O2max), V(O2max)/kg, anaerobic thresh-old(AT), oxygen pulse(V(O2)/HR), breath reserve(BR), inhale time (VTin), expiratory time(VTex) and ventilato-ry equivalent for CO(2)(EqCO(2))were measured by CPX and compared by using one-way ANOVA. Results: Compared to the control group (1 620±400) L/min, the maximal oxygen uptake(V(O2max)) in obese group(1 905±592) L/min and extremely obese group (2 131.09±541.86) L/min were significance higher (F=5.14, P<0.01). The V(O2max)/kg in obese group (19±5) L·min(-1)·kg(-1) and extremely obese groups (16±4) L·min(-1)·kg(-1) were sig-nificant lower than those in control group(27±5)L·min(-1)·kg(-1) (F=35.37,P<0.01). Compared to the control group (9.3±1.4)L·min(-1)·W(-1), the change of oxygen uptake required under certain exercise load (ΔV(O2)/ΔWR) in obese group(9.0±1.7) L·min(-1)·W(-1)and extremely obese group (8.7±2.2) L·min(-1)·W(-1) were no significant difference (F=0.67,P=0.51). The AT in obese group (1 114±391) L/min and extremely obese group (1 348±349) L/min were significant higher than those in control group (832±223) L/min (F=12.85,P<0.01). Com-pared to the control group(10±4) L·min(-1)·b(-1), V(O2)/HR in obese group (12±3) L·min(-1)·b(-1) and extremely obese group(14±3) L·min·b(-1) were significance higher (F=8.16, P<0.01). No significant difference was found between the three groups in BR, VTin, VTex and EqCO(2). Conclusion: obese and extremely obese individu-als have a decreased ablity to exercise when the body requires anaerobic metabolism to provide energy. As exercise power increases, the heart oxygen consumption per stroke and the amount of volume and oxygen re-quired for gax exchange does increase.

[Relative factors of transmural intestinal necrosis in acute superior mesenteric vein thrombosis].

Objective: To examine the relative factors of transmural intestinal necrosis (TIN) during multidisciplinary stepwise management facilitating the decision making in patients with acute superior mesenteric vein thrombosis (ASMVT). Methods: Clinical data of patients with ASMVT admitted to Department of General Surgery, Jinling Hospital from January 2009 to June 2017 were reviewed retrospectively. There were 52 males and 37 females, aging (45.9 ± 12.6) years (range: 20 to 69 years). According to the postoperative pathological results and follow-up, the patients were divided into TIN group (n=31) and non-TIN group (n=58, including 18 cases of intestinal stricture). The related factors were compared between ASMVT patients with TIN and patients without TIN by univariate analysis using t test, U test and χ(2) test accordingly, and factors with statistically significance were subsequently submitted to binary Logistic regression analysis. The predictive value and cut-off point of factors were evaluated by receiver operator characteristic (ROC) curve and area under the curve. Results: In univariate analysis, smoking, hypertension, peritonitis, white blood cell count,haemoglobin, international normalized ratio, blood albumin, thrombosis of superior mesenteric branches vein, free intraperitoneal fluid, decrease of bowel wall enhancement and pneumatosis intestinalis were TIN risk factors (all P<0.05). According to the binary Logistic regression analysis, white blood cell count (OR=1.093, 95%CI: 1.010 to 1.182, P=0.027), thrombosis of the superior mesenteric branches vein (OR=11.519, 95%CI: 1.906 to 69.615, P=0.008), pneumatosis intestinalis (OR=11.140, 95%CI: 2.360 to 52.585, P=0.002) were independent relative factors of TIN in patients with AMI, and the area under the ROC curve of the above factors and predictive model was 0.759 (95%CI: 0.647 to 0.871), 0.745 (95%CI: 0.641 to 0.848), 0.737 (95%CI: 0.621 to 0.854), 0.909 (95%CI: 0.847 to 0.971), respectively. The cutoff value of white blood cell count was 18.1 × 10(9)/L. Conclusion: White blood cell levels, superior mesenteric vein branch thrombosis and pneumatosis intestinalis are independent predictors of TIN in ASMVT.

[The status analysis of diagnosis and treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China: a report of 1 003 cases in 16 domestic medical centers].

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ(2) test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ(2)=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions: It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.

[Analysis on the incidence of occupational pneumoconiosis of migrant workers in Shiyan city from 2013 to 2017].

Objective: To explore the incidence regularity and characteristics of pneumoconiosis among migrant workers in Shiyan city, and to provide a basis for making policies about pneumoconiosis prevention and treatment among migrant workers. Methods: In September 2018, 338 cases of pneumoconiosis among migrant workers and 354 cases of pneumoconiosis among non-migrant workers were collected between 2013 and 2017. The proportions of pneumoconiosis types, the age and seniority of onset workers, the severity grade of pneumoconiosis, the type of pneumoconiosis, the type of work and regional distribution, etc. were analyzed. Results: The age at onset of pneumoconiosisand the length of service of migrant workers and non-migrant workers in Shiyan city were significantly different (t=2.237, 3.208, P<0.05) . The proportion of pneumoconiosis stage was significantly different from that of non-migrant workers (χ(2)=47.897, P<0.05) , among migrant workers, the types of pneumoconiosis were mainly silicosis (308 cases, 91.1%) , coal worker's pneumoconiosis (29 cases, 8.6%) . The leading work types are rock drilling (115 cases, 34.0%) and blasting (105 cases, 31.1%) . The industry was mainly engaged in non-ferrous metal mining (205 cases, 60.7%) and coal (105 cases, 31.1%) . The area distribution involved each counties of Shiyan city, with Zhushan county (175 cases, 51.8%) and Yunxi county (125 cases, 37.0%) as the top two districts in number of cases. Of the cases of migrant workers, 89 cases (26.3%) had blood relationship with any others. There was no work-related injury insurance for migrant workers with pneumoconiosis. Conclusion: There is a high incidence of pneumoconiosis among migrant workers in Shiyan city, featured with the phenomenon of "late occurrence" and "family clustering", so it is urgent to strengthen the prevention and treatment of pneumoconiosis of migrant workers.

A method for improving the accuracy of non-invasive prenatal screening by cell-free foetal DNA size selection.

Background Non-invasive prenatal screening (NIPS) using cell-free foetal DNA (cfDNA) has been widely used for identifying common foetal aneuploidies (e.g. trisomy 21 (T21), trisomy (T18) and trisomy 13 (T13)) in clinical practice. The sensitivity and specificity of NIPS exceeds 99%, but the positive prediction value (PPV) is approximately 70% (combined T21, T18 and T13). Thus, some 30% of pregnant women who have positive NIPS results are eventually identified as normal by amniocentesis. These women therefore must undertake needless invasive tests and risk miscarrying healthy babies because of false positive NIPS results. Methods In order to achieve higher accuracy, we amended the standard NIPS (s-NIPS) protocol with an additional cfDNA size selecting step in agarose-electrophoresis. The advantage of the new method (named e-NIPS) was validated by comparing the results of e-NIPS and s-NIPS using 114 retrospective cases selected from 15,930 cases. Results Our results showed that the foetal cfDNA fraction can be enriched significantly by a size selection step. With this modification, all 98 negative cases and 9 of 11 false positive cases of s-NIPS were correctly identified by e-NIPS, resulting in an increased PPV from 71% to 77%. Additionally, a simulation test showed that e-NIPS is more reliable than s-NIPS, especially when the foetal cfDNA concentration and sequencing coverage are low. Conclusion cfDNA size selection is an important step in improving the accuracy of non-invasive prenatal screening for chromosomal abnormalities.

[Exogenous lipid pneumonia with hyperpyrexia: a case report].

Lipoid pneumonia (LP) is an uncommon form of pneumonia that is characterized by the presence of intra-alveolar lipid and lipid-laden macrophages on microscopy. It categorized as exogenous lipoid pneumonia (ExLP) and endogenous lipoid pneumonia (EnLP). Exogenous lipoid pneumonia caused by inhalation of liposuction substances (animal fat, vegetable oil, or mineral oil), mostly, in adult cases, they were medicines for constipation or rhinopharyngitis. Most of these patients showed mild clinical manifestations, and chronic medical condition. There were reports of lipoid pneumonia being successfully treated with corticosteroids, immunoglobulins and whole lung lavage. We report a case of exogenous lipoid pneumonia characterized by high fever and acute medical condition. A 77-year-old woman with hypertension and diabetes mellitus, accepted paraffin oil treatment for "incomplete intestinal obstruction", then, an accident of aspiration happened, as she went through the history of coughing while eating, followed by persistent hyperthermia and increases of white blood cells (WBC). Chest CT showed progressive ground-glass opacities, accompanied with fusion of consolidation, her sputum etiological examination was negative, and the therapy of broad-spectrum antibiotic was invalid. The patient was subjected to bronchofibroscopy with bronchoalveolar lavage (BAL). The bronchoalveolar lavage fluid (BALF) appeared colorless and transparent, and did not show a milky appearence. Total cell count of the BALF was 2.0×109 cell/mL, including 7.2% macrophages and 92.8% neutrophils. Cultures of the BALF were negative for bacterial, fungal, and mycobacterial pathogens. The BALF cytologic findings showed vacuolated lipid-laden macrophages (Oil Red O staining). These findings revealed exogenous lipoid pneumonia. There were reports of lipoid pneumonia being successfully treated with corticosteroids, immunoglobulins, and whole-lung lavage. So this patient was treated with methylprednisolone 120 mg/d for 3 days and 80 mg/d for 6 days, at the same time, immunoglobulins was given to infusion, but the daily peak temperature of the patients fluctuated between 38 and 39 degrees. Then, whole lung lavage was performed 28 days after admission. Unfortunately, acute pulmonary edema occurred during the operation, as the tracheal intubation problems, and 6 days later, the patient died at last. The clinical manifestations of exogenous lipid pneumonia vary greatly, from asymptomatic to life-threatening symptoms, and as febrile low fever is the main manifestation, but hyperthermia may also be the remarkable presentation.