Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.

Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 12, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 post infection, and died at the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of severe COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Fatal Outcome ; Hemorrhage/virology* ; Humans ; Lung/pathology* ; Myocardium/pathology* ; Pandemics ; Pneumonia, Viral/pathology* ; Retrospective Studies ; SARS-CoV-2

OBJECTIVE: To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients. METHODS: 53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing. RESULTS: 21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy. CONCLUSION A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.
Chromosomes, Human, Pair 11 ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute ; Mutation ; Prognosis ; fms-Like Tyrosine Kinase 3

Adaptor Proteins, Signal Transducing ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Peptide Hydrolases ; Prognosis ; Ubiquitin-Protein Ligases

Objective To understand the awareness of AIDS related knowledge, high risk behaviors, the infection status of HIV, syphilis and HSV-2, and to explore the associated factors with HSV-2 infection among whoremasters in Kaiyuan City, so as to provide scientific evidence for targeted intervention to prevent and control HIV and other STDs. Methods A self-designed questionnaire survey was conducted among whoremasters recruited through outreach activities and snowball sampling. The blood and urine were also collected for corresponding laboratory examination. Results Among the whoremasters, 98.22% had a high awareness of AIDS related knowledge, 9.33% once used drugs, and 14.67% did not use a condom during the latest commercial sex. 62.22% of the whoremasters ever had non-marital sex partners, and of those who had sex with non-marital sex partners in the past year, 59.55% reported using condoms inconsistently. The total infection rate of HIV/syphilis/HSV-2 was 18.22% and the infection rates of HIV, syphilis and HSV-2 were 3.11%, 1.33% and 16.44%, respectively. The older whoremasters were more likely to have a higher HSV-2 infection rate (AOR=1.044,95%CI:1.016-1.073,P=0.002), and those whoremasters not using a condom during the latest commercial sex were more likely to have a higher HSV-2 infection rate (AOR=3.125,95%CI:1.229-7.945,P=0.017). Conclusions Though whoremasters in Kaiyuan City had a high awareness of AIDS related knowledge, they had high-risk behaviors and relatively high HIV and other STDs infection rates. Targeted interventions are needed to improve the risk awareness of STDs infection to promote consistent condom use in both commercial and non-marital sexual behaviors among whoremasters.

BackgroundThe aim of the study was to evaluate the long-term safety and efficacy of the Trabectome for Chinese glaucoma patients.

MethodsThis was a multicenter, retrospective, observational study. Glaucoma patients, except those with neovascular glaucoma, with/without a visually significant cataract were enrolled. The patients received Trabectome or a combined surgery with phacoemulsification and intraocular lens implantation. The primary outcome evaluation was a reduction in intraocular pressure (IOP), and the secondary outcomes were a reduction in glaucoma medication, the 2-year success percentages, and complications. Success was defined as an IOP <21 mmHg and at least a 20% IOP reduction from baseline after 3 months for any two consecutive visits, without additional glaucoma surgery. The data were processed using the R Stats Package version 3.0.0. The Wilcoxon test was used to compare the postoperative IOP and the number of glaucoma medications with baselines. The Kaplan-Meier test was used to calculate the 2-year success percentage. The risk factors related to Trabectome failure were determined by logistic regression.

ResultsA total of 120 glaucoma patients were enrolled. The Trabectome efficiently reduced the IOP from a baseline of 22.8 ± 1.34 mmHg to 17.6 ± 0.96 mmHg, and the use of glaucoma medications from 2.2 ± 0.17 mmHg to 1.4 ± 0.21 in a 2-year follow-up (both, P < 0.01). The overall success percentage was 80%. No risk factor related to Trabectome failure was identified. No vision-threatening complication was observed. Ten patients, who required secondary glaucoma surgery, all reached the target IOP.

ConclusionsIn a 2-year follow-up, Trabectome was an efficient and safe procedure for Chinese glaucoma patients.

Adolescent ; Adult ; Female ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Young Adult

In the present study, we evaluated the impact of sperm origins and concentration on the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles. A total of 1201 ICSI cycles were retrospectively analyzed for male azoospermia or oligozoospermia between January 2015 and December 2015 in the Peking University Third Hospital. Patients were divided into three groups (Group 1 vs Group 2/3; surgically extracted sperm vs ejaculated sperms): Group 1 included 343 ICSI cycles and Group 2 analyzed 388 cycles on semen with sperm concentration <5 × 10⁶ ml^-1 (severe oligozoospermia group). Group 3 included 470 cycles with sperm concentration between 5 × 10⁶ ml^-1 and 15 × 10⁶ ml^-1 (mild oligozoospermia group). Fertilization rates, clinical pregnancy rates, and live birth rates were analyzed and compared among groups of different semen origins and concentrations on the oocyte retrieval day. Group 2 showed a lower fertilization rate than Group 3 (62.9% ± 21.6% vs 66.8% ± 22.1%,P< 0.05). There were no statistically significant differences in clinical pregnancy rate per transfer (51.3%, 46.7%, and 50.0%, respectively), live birth rate per transfer (44.4%, 40.9%, and 41.4%, respectively), accumulative live birth rate (58.3%, 51.0%, and 52.1%, respectively), twin birth rate (18.4%, 10.6%, and 12.6%, respectively), and birth defects rate (0, 0.3%, and 0.2%, respectively) among three groups. The results of this study indicated that sperm origins and concentration do not impact the clinical outcomes in ICSI cycles.
Adult ; Azoospermia/diagnosis* ; Birth Rate ; Female ; Humans ; Live Birth ; Male ; Oligospermia/diagnosis* ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Semen Analysis ; Sperm Injections, Intracytoplasmic/methods*

OBJECTIVETo study the relationship between surface markers of CD56 and CD19 and karyotypes and prognosis in multiple myeloma.

METHODSA total of 126 cases of newly diagnosed multiple myeloma in the first hospital of Peking university from 2011 to 2015 were enrolled in this study. Cytogenetic abnormalities and immunophenotypes were detected by using fluorescence in situ hybridization and flow cytometry respectively before chemotherapy. Bone marrow smear was used for detection of abnormal plasma cell infiltration. By combining with their basic data, the relationship between immunophenotypes, cytogenetics and prognosis of MM was analyzed.

RESULTS(1) The median of myeloma cells in the 126 patients was 0.24（0.01-0.97）; the median of myeloma cells in 116 patients who have immunophenotype datas was 0.25（0.01-0.97）； the median of myeloma cells in CD19 positive patients was 0.11（0.01-0.53）; the median of myeloma cells in CD19 negative patients was 0.26（0.01-0.97）. The median of myeloma cells in CD19 positive patients was much lower than that in CD19 negative patients（P=0.036）. (2)In 116 patients detected by the immunophenotype, the myeloma cells expressed CD19,CD20,CD56 and CD117. Compared with CD56 negative patients(45/116,38.79%),CD56 positive patients(71/116,61.21%) had a clearly favorable disease outcome（OS was 53.0 month vs 31.0 month,P=0.016; PFS was 37.5 months vs 18.4 months, P=0.036）. (3)CD19 positive patients was 16.38%（19/116）,CD19 negative patients was 83.62%（97/116）； CD19 positive MM and CD19 negative MM had no difference in OS and PFS. (4)CD117 positive rate in CD19 positive patients was 42.11%(8/19), the CD117 positive rate in CD19 negative patients was 18.57%(18/97), the CD19 expression positively correlated with CD117 expression. (5)FISH detection was done for 67 newly diagnosed MM patients, 8 patients showed normal karyotypes(11.94%), 59 patients had abnormal karyotypes(88.06%). The most common abnormal karyotypes were IgH rearragement which occurred in 47 patients(70.15%). Other abnormal karyotypes included 1q21+, del(13q14),del(13q14.3),del(17p13) . These abnormal karyotypes occurred in 37 patients（55.22%）,31 patients（46.27%）,33 patients（49.25%） and 13 patients（19.40%） respectively. In comparison with CD19 negative MM patients, the incidence rate of 1q21+ and del(13q14.3) was significantly lower in CD19 positive patients(1q21+:33.33% vs 61.54%,P=0.016; del(13q14.3): 33.33% vs 53.85%,P=0.043）.

CONCLUSIONThe prognosis of CD56 positive MM patients is better than that of CD56 negative MM patients, CD19 negative MM has more abnormal karyotypes and bone marrow infiltration,but they have no statistical prognostic differences.