[Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis].

Objective: To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM. Methods: Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression. Results: A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly (OR=1.06, P=0.048 ) , hyponatremia(OR=0.81,P=0.020), high protein level in cerebrospinal fluid (CSF) (OR=3.32,P=0.033), cerebral infarction(OR=10.50,P=0.040) and hydrocephalus(OR=8.51,P=0.049) were associated with poor prognosis in TBM patients. Conclusions: The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

[Characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza].

Objective: To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza. Methods: This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups. Results: A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4(+)T, CD8(+)T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/µl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/µl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/µl respectively]. Meanwhile, the T cells and CD8(+)T counts in fatal patients [370 (260,537) cells/µl and 87 (74,105) cells/µl] were significantly lower than those in severe and alive patients [722 (390,990) cells/µl and 222 (154,404) cells/µl]. CD8(+)HLA-DR/CD8(+)and CD8(+)CD38(+)/CD8(+)T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8(+)HLA-DR/CD8(+)count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8(+)T cell count (OR=0.952, 95%CI 0.910-0.997, P=0.035) and CD8(+)HLA-DR/CD8(+)T (OR=0.916, 95%CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later. Conclusions: All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8(+)T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

[A randomized controlled study of peramivir, oseltamivir and placebo in patients with mild influenza].

Objectives: To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza. Methods: This was a randomized, double-blind, double-dummy, placebo and positive control, multicenter clinical trial, comparing peramivir trihydrate with oseltamivir and placebo. The inclusive criteria were 15-70 years old, onset within 48 h, positive rapid influenza antigen test, and febrile (>38℃) accompanied with at least two associated symptoms. The severe cases complicated with chronic pulmonary and cardiac diseases, malignancies, organ transplantation, hemodialysis, uncontrolled diabetes, immunocompromised status, pregnancy and coexistence of bacterium infections were excluded. All patients were randomized 2∶2∶1 to receive peramivir, oseltamivir and placebo respectively. The primary endpoint was the disease duration, the secondary endpoints included time to normal axillary temperature and normal living activities, viral response, and adverse effects. Results: Following informed consent, 133 patients were included in this study. Four patients were exclude due to missing medical records, not fitting inclusion or exclusion criteria and poor compliance. A total of 129 patients were finally analyzed, including 49 cases, 54 cases and 26 cases in peramivir group, oseltamivir group and placebo group. The median disease duration were 96 (76, 120) hours, 105 (90,124) hours, and 124 (104, 172) hours in three groups respectively (P>0.05) . The time to normal axillary temperature, normal living activities and viral response were not significantly different in three groups (P>0.05) . Conclusion: The value of antiviral therapy in patients with mild influenza needs to be further determined.

[The evaluation of training program "resident team leader in the Department of General Internal Medicine" at Peking Union Medical College Hospital].

Objective: To evaluate senior resident training program "resident team leader in the Department of General Internal Medicine" at Peking Union Medical College Hospital. Methods: We surveyed the residents or the fellows who had been selected as resident team leaders and received the training from October 2014 to September 2018 on their comments and suggestions. Results: Twenty-two rotated senior residents who were selected as team leaders in the Department of General Internal Medicine completed the survey. Almost all (21/22, 95.5%) of the respondents reported that they learnt more in general as team leaders by Visual Analog Scale (VAS). The mean VAS scores of clinical skills were 7.23±1.27, 7.86±1.32 in teaching abilities, 8.14±0.89 in leadership evaluation. Scales as chief resident assistants were 8.44±1.26. Sixteen respondents (72.7%) considered that pre-job training by attending doctors was necessary. Another 8 (36.4%) respondents addressed their demands on training of teaching skills. Conclusions: The senior resident training program "resident team leader in the Department of General Internal Medicine" improves the competency of rotated senior residents. It is a valuable pilot study on senior resident training and worthy of further application in other departments and hospitals.

MiR-126 induces myeloma cell line Karpas707 apoptosis by downregulating anti-apoptotic protein MCL.

OBJECTIVE: Myeloma seriously threats human life and health and needs more efficacy treatment method in the clinic. MiR-126 regulates cell proliferation and apoptosis. This study explores the regulatory role of miR-126 in myeloma and related molecular mechanism. MATERIALS AND METHODS: MiR-126 and control were synthesized and transfected to myeloma cell line Karpas707 using Lipofectamine. Cell apoptosis was evaluated by MTT assay, caspase-3 activity detection, and flow cytometry. Myeloid cell leukemin (MCL) siRNA and plasmid were transfected to Karpas707 cells to test its impact on cell apoptosis. RESULTS: MTT assay revealed that miR-126 significantly restrained Karpas707 cell growth (p=0.0017). Cell apoptosis detection showed that miR-126 significantly promoted phosphatidylserine eversion and caspase-3 activation (p=0.031), and downregulated MCL level (p=0.017). MCL siRNA markedly enhanced Karpas707 cell apoptosis induced by miR-126 (p=0.024), while the MCL overexpression apparently inhibited Karpas707 cell apoptosis induced by miR-126 (p=0.0073). CONCLUSIONS: MiR-126 induces Karpas707 cell apoptosis by downregulating anti-apoptotic protein MCL, which provides a theoretical basis for the target selection of myeloma.

[Clinical features of adult patients with chronic active Epstein-Barr virus infection].

Objective: To investigate the clinical features of adult-onset chronic active Epstein-Barr virus infection (CAEBV). Methods: A total of 21 adult patients with CAEBV who were admitted to the department of General Internal Medicine at Peking Union Medical College Hospital from January 2006 to January 2016 were retrospectively analyzed. Demographic data, disease duration, clinical manifestations, laboratory findings, treatments and prognosis were reviewed. Results: Eighteen females and 3 males were enrolled with a mean age of 39 years. The most common clinical manifestations included fever in 20 patients, splenomegaly in 20 patients, lymphadenopathy in 18 patients, and hepatomegaly in 10 patients, followed by laryngopharyngeal disorders in 6 patients, pleural effusion and peritoneal effusion each in 5 patients, rash in 4 patients, interstitial lung disease in 3 patients, gastrointestinal hemorrhage in 2 patients, and peripheral neuropathy and pulmonary hypertension each in 1 patient. Six patients were complicated with hemophagocytic lymphohis-tioncytosis(HLH) that developed 5-17 (mean: 9) months following CAEBV onset, all of whom experienced hyperpyrexia, pancytopenia, lymphadenopathy, splenomegaly, and liver dysfunction, 3 with hepatomegaly. Nineteen of the 21 patients had received steroid therapy including 10 combined with immunosuppressive agents, 11 with antiviral therapy, and 8 with intravenous immunoglobulin. Thirteen patients died, including 10 of multiple organ failure, (including 6 of HLH) 2 of severe pulmonary infection, and 1 of lymphoma. Six patients remained on follow-up, yet 2 were missing. Conclusions: CAEBV is expected with severe condition and poor prognosis, which is likely to be complicated with HLH. Clinical physicians should pay attention to adult patients with fever, hepatosplenomegaly and lymphadenopathy, which suggests possible CAEBV.

Lonomia caterpillar envenoming in French Guiana reversed by the Brazilian antivenom: A successful case of international cooperation for a rare but deadly tropical hazard.

In the American continent, larval forms (caterpillars) of the Lonomia genus can cause systemic reactions in human beings. In this Paper, we report the third case of Lonomia envenoming recorded in French Guiana in 25 years, and the first in which specific antivenom was administered. Severe symptoms of the envenoming were observed in our patient including pain; coagulopathy and systemic hemorrhage. They are caused by skin contact with caterpillars. Recovery, however, was quite satisfactory thanks to the international cooperation of the health authorities in both France and Brazil.

NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans.

Using a meta-analysis framework, we investigated the association between the NLRP3 rs35829419 polymorphism and increased susceptibility to diverse diseases in humans. Relevant published studies were identified through a comprehensive and systematic electronic search, using the following scientific literature databases: Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, Chinese Biomedical, the Chinese Journal Full-Text, and the Weipu Journal. Statistical analysis of data extracted from the selected high quality studies was performed using the Version 12.0 STATA software. A total of 13 case-control studies met our stringent inclusion and exclusion criteria for the present meta-analysis. These 13 high quality studies contained relevant information on 7719 patients with various diseases and 7094 healthy controls. Our meta-analysis results showed that the NLRP3 gene rs35829419 C>A polymorphism was associated with a significantly increased risk of developing multiple diseases in humans under 5 genetic models (all P < 0.05). Data stratification and subgroup analysis based on the disease type revealed that rs35829419 C>A carriers displayed a markedly increase susceptibility to leprosy, colorectal cancer, HIV-1 infection, rheumatoid arthritis, abdominal aortic aneurysms, inflammatory bowel disease, ulcerative colitis, and atopic dermatitis. In summary, our meta-analysis results revealed the first identified strong correlation between the NLRP3 rs35829419 polymorphism and increased susceptibility to various diseases in humans.

Differential expression of COX-2 in osteoarthritis and rheumatoid arthritis.

In this study, we investigated the differential expression profiles of cyclooxygenase-2 (COX-2) mRNA and proteins in osteoarthritis (OA) and rheumatoid arthritis (RA) patients to elucidate the role of COX-2 expression in the pathogenesis and development of these diseases and to provide novel drug targets for treating arthritis. A total of 60 patients who received arthroscopic surgeries for treating OA (N = 30) or RA (N = 30) were examined. Fifteen normal synovial tissue samples were included as the control group. Fibroblastic synovial cells in all samples were cultured in vitro and COX-2 mRNA, protein expression levels, and COX-2 levels were detected in synovial fluids by real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay methods, respectively. The mRNA level of COX-2 was significantly elevated in synovial cells from OA and RA patients compared to that in control samples (P < 0.05). COX-2 mRNA level was significantly higher in synovial cells from OA patients than in those from RA patients (P < 0.05). Consistent results were obtained for COX-2 protein expression levels from patients' synovial samples. In synovial fluids, OA (P < 0.05), but not RA (P > 0.05), patients showed significantly higher COX-2 levels compared to the control group. Elevated synovial COX-2 expression facilitates the pathogenesis of OA and RA, and thus this index reflects the condition of these 2 diseases.

Transplantation of both kidneys from one donor rat using end-to-end vascular anastomosis in normal saline.

BACKGROUND: End-to-end vascular anastomosis in the 0.9% NaCl solution was compared with conventional end-to-end vascular anastomosis in the model rat, with two kidneys from one donor rat harvested and transplanted to two recipient rats. METHODS: Two methods of suturing renal walls were used. In group A, the conventional end-to-end anastomosis was performed, where one person stitched veinous walls while the other washed them using the normal saline (n = 20). In group B, end-to-end anastomosis of renal vein walls was performed in 0.9% NaCl solution (n = 20). RESULTS: In the normal saline, the renal vein walls naturally extended and separated and the edges of the renal veins were revealed. In group B, the operation time and overall complication rate of suturing were reduced (P < .001). CONCLUSION: This is the first report of end-to-end vascular anastomosis in the normal saline in the model of rat kidney transplantation. This method, which does not require any special instruments, is fast, safe, and needs only one surgeon to perform the renal vascular suturing, and may be applied to other transplantation models.

Epidemiologic and clinical survey of victims of centipede stings admitted to Hospital Vital Brazil (São Paulo, Brazil).

We retrospectively analyzed 98 proven cases of centipede stings admitted to Hospital Vital Brazil, Butantan Institute, São Paulo, Brazil, between 1990 and 2007. Most stings occurred at the metropolitan area of São Paulo city (n=94, 95.9%), in the domiciles of patients (n=67, 68.4%), and during the warm-rainy season (n=60, 61.2%). The mean age of the victims was 32.0+/-18.8-years-old. Cryptops and Otostigmus genera were responsible for most cases. Around 86% of the patients sought medical care within 6h after the sting. Both lower (56.1 %) and upper limbs (41.8 %) were most frequently bitten, especially the feet and hands (89.8%). The most frequent local clinical manifestations were pain (94.9%), erythema (44.9%) and edema (21.4%), and the latter was mainly observed in patients bitten by Otostigmus spp. Supportive treatment was used in only 28.6% of the patients, namely administration of local anesthesia (9.2%) and systemic analgesia (13.3%). No sequels or complications were observed in patients, and the prognostic was benign.

Failure of chloramphenicol prophylaxis to reduce the frequency of abscess formation as a complication of envenoming by Bothrops snakes in Brazil: a double-blind randomized controlled trial.

Bites by many species of venomous snake may result in local necrosis at, or extending from, the site of the bite. The use of prophylactic antibiotics to prevent infection as a complication of local necrotic envenoming is controversial. A double-blind randomized controlled trial was carried out to assess whether antibiotic therapy is effective in this situation. Two hundred and fifty-one patients, with proven envenoming by snakes of the genus Bothrops, admitted to two hospitals in Brazil, between 1990 and 1996, were randomized to receive either oral chloramphenicol (500 mg every six hours for five days) or placebo. One hundred and twenty-two of these patients received chloramphenicol (group 1) and 129 were given placebo (group 2). There were no significant differences between the groups at the time of admission. Necrosis developed in seven (5.7%) patients in group 1 and in five (3.9%) patients in group 2 (P>0.05) while abscesses occurred in six patients (4.9%) in group 1 and in six (4.7%) patients in group 2 (P>0.05). In conclusion, the use of orally-administered chloramphenicol for victims of Bothrops snake bite with signs of local envenoming on admission, is not effective for the prevention of local infections.

Envenoming by Bothrops jararaca in Brazil: association between venom antigenaemia and severity at admission to hospital.

The association between the clinical severity of Bothrops jararaca envenoming at admission and serum venom and plasma fibrinogen concentrations before antivenom administration is reported in 137 patients admitted to Hospital Vital Brazil, Instituto Butantan, São Paulo, Brazil, between 1989 and 1990. Other variables such as age, gender, site of the bite, use of tourniquet and the time interval between the bite and start of antivenom therapy, spontaneous systemic bleeding, and the 20 minute whole blood clotting test (20WBCT) at admission showed no association with either severity or serum venom antigen concentration (SVAC). Mean SVAC in patients with mild envenoming was significantly lower than in the group with moderate envenoming (P = 0.0007). Patients with plasma fibrinogen concentrations > 1.5 g/L had a lower mean SVAC than patients with plasma fibrinogen concentrations < or = 1.5 g/L (P = 0.02). Those admitted with a tourniquet in place had significantly higher plasma fibrinogen concentrations than those without a tourniquet (P = 0.002). A multiple logistic regression model showed independent risk factors for severity: bites at sites other than legs or forearms, SVACs > or = 400 ng/mL, and the use of a tourniquet. Rapid quantification of SVAC before antivenom therapy might improve initial evaluation of severity in B. jararaca bites.

Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites.

OBJECTIVE: To investigate the efficacy of the H1 antihistamine promethazine against early anaphylactic reactions to antivenom. DESIGN: Sequential randomised, double blind, placebo controlled trial. SETTING: Public hospital in a venom research institute, São Paulo, Brazil. PARTICIPANTS: 101 patients requiring antivenom treatment after being bitten by bothrops snakes. INTERVENTION: Intramuscular injection of promethazine (25 mg for adults and 0.5/kg for children) or placebo given 15-20 min before starting intravenous infusion of antivenom. MAIN OUTCOME MEASURES: Incidence and severity of anaphylactic reactions occurring within 24 hours after antivenom. RESULTS: Reactions occurred in 12 of 49 patients treated with promethazine (24%) and in 13 of 52 given placebo (25%); most were mild or moderate. Continuous sequential analysis indicated that the study could be interrupted at the 22nd untied pair, without preference for promethazine or placebo. CONCLUSION: Prophylaxis with promethazine does not prevent early reactions. Patients should be observed carefully during antivenom infusion and the subsequent few hours.

A clinical and epidemiological study of Loxosceles spider envenoming in Santa Catarina, Brazil.

A clinical and epidemiological study of 267 cases of envenomation by Loxosceles spp. (loxoscelism), notified to Centro de Informações Toxicológicas de Florianópolis (Santa Catarina State, Brazil), was conducted between January 1985 and December 1995. Most of the incidents occurred along the coast of the mid-southern region of the state, during the warmest months. L. laeta and L. intermedia were identified as the causative agents. Cutaneous loxoscelism was clinically diagnosed in 232 (86.9%) patients with local pain (86.5%), oedema (80.5%), hyperaemia (79.8%) and necrosis (56.9%). Cutaneous-visceral loxoscelism was detected in 35 patients (13.1%) with intravascular haemolysis, manifested by jaundice (68.6%), oliguria (45.7%), dark urine (28.6%), haemorrhage (25.7%), anuria (8.6%) and shock (2.9%), besides the cutaneous effects. Specific antivenom was given to 125 patients (46.8%) and only 8 (6.5%) had mild reactions. Acute renal failure was observed in 17 cases (6.4%); 4 patients (1.5%) died, all of whom were children under 14 years old.