Objective:Early identification of ischemic stroke patients with large vessel occlusion can improve referral efficiency and shorten reperfusion time. The purpose of this study was to analyze the characteristics of patients with large vessel occlusion and identify factors that could predict large vessel occlusion.Methods:The clinical data of 432 patients with ischemic stroke treated through emergency green channel were retrospectively analyzed, and the differences between the large vessel occlusion group (LVO group) and the non-large vessel occlusion group (non-LVO group) were compared, and two independent risk factors of the LVO group were screened out by logistics regression analysis: baseline NIHSS score and D-dimer value. The predicted cutoff values of NIHSS score and D-dimer were further determined by the receiver operating characteristic (ROC) curve.Results:A total of 432 patients with ischemic stroke had complete imaging data, with a mean age of 68.5±12.4 years, including 275 (63.7%) males, and 245 (56.7%) in the LVO group and 187 (43.3%) in the non-LVO group. Age, hemorrhagic transformation, thrombolytic therapy, endovascular treatment, atrial fibrillation, baseline NIHSS score [14.0 (6.0-20.0) vs. 3.0 (1.0-6.0), P<0.05], and D-dimer value at admission [0.9(0.4-2.3) mg/L vs. 0.3 (0.2-0.5)mg/L, P<0.05] were statistically significant different between the two groups. Multivariate Logistic regression analysis showed that higher baseline NIHSS score( OR=1.22,95% CI: 1.17-1.27)and higher D-dimer value( OR=3.10,95% CI: 2.14-4.47)were independent risk factors for large vessel occlusion. Baseline NIHSS score combined with D-dimer value was a good predictor of large vessel occlusion(AUC 0.85 [0.81-0.89]). ROC curve suggested that NIHSS score >6.5 and D-dimer >0.57 mg/L were the cutoff values for predicting large vessel occlusion. Conclusions:Higher baseline NIHSS score and D-dimer value are valuable for early prediction of large vessel occlusion, patients with NIHSS score >6.5 points and D-dimer >0.57 mg/L should be promptly transported to an advanced stroke center for treatment.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

Objectives:the purpose of this study was to systematically evaluate the clinical value of cytokines in autoimmune diseases (AID). It was a kind of complex disease, and its pathogenesis involved cytokines, autoantibodies, immune cells and other immune factors. Especially some AID, such as Adult still′s disease (AOSD) and Takayasu arteritis(TA), had no specific biomarkers at present. This study was a retrospective case-control study.Methods:the data of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) in 834 AID patients from January 2019 to August 2022 were collected, and the serum levels of those cytokines in 30 healthy controls (HC) were detected at the same time. And AOSD, TA, systemic lupus erythematosus (SLE) and Behcet′s syndrome (BS) were divided into active group and inactive group. In addition, we also made a subgroup analysis of two important organs involved in SLE (kidney and nervous system). GraphPad Prism 9 and R 4.2.2 software were used. Nonparametric tests (Kruskal-Wallis H test, Mann-Whitney U test) were used to compare the differences among groups, and Dunn′s method was used to correct the false positive caused by multiple tests. Results:To compare the level of IL-6 in each group, except Behcet syndrome (BS) group and antiphospholipid syndrome (APS) group, the serum IL-6 level of AID group was higher than that of HC group, with antineutrophil cytoplasmic antibodies associated vasculitis(AAV) [3.85(2.00,8.55) pg/ml], idiopathic inflammatory myopathies(IIM) [7.80(2.50,6.50)pg/ml], IgG4-related disease(IgG4RD) [3.65(2.08,12.83) pg/ml], rheumatoid arthritis (RA) [5.50(2.20,16.10) pg/ml], SLE[4.70(2.75,16.55) pg/ml], Sj?gren syndrome(SS) [3.20(2.00,8.90) pg/ml], systemic sclerosis(SSc) [2.70(2.00,8.90) pg/ml], TA[3.40 (2.00,6.50) pg/ml], other AID diseases[4.40(2.00,11.10) pg/ml], especially AOSD [15.20(2.10, 39.20) pg/ml]. After correction, the differences were statistically significant ( P c<0.05). At the same time, the levels of serum TNF-α [7.40(5.60,10.95) pg/ml]and IL-10 [5.00(5.00, 7.58) pg/ml] in AOSD group were significantly higher than those in HC group[7.15(5.93,8.00) pg/ml,5.00(5.00,5.00) pg/ml] after correction ( P c<0.05). At the same time, the levels of serum TNF-α and IL-10 in AOSD group were higher than those in HC group. The serum levels of IL-6 and IL-8 in patients with active AOSD, BS, SLE and TA were significantly higher than those in patients without active disease (all P<0.05). In addition, the level of serum IL-8 in lupus nephritis group was significantly higher than that in non-lupus nephritis group ( P<0.05). At the same time, the serum levels of IL-6, IL-8 and TNF-α in neuropsychiatric lupus erythematosus group were significantly higher than those in non-neuropsychiatric lupus erythematosus group ( P<0.05), but there was no significant difference in IL-10 between neuropsychiatric lupus group and non-neuropsychiatric lupus erythematosus group. Conclusions:there was a close relationship between AID and cytokines. At present, the change of serum IL-6 level was the most classic one in clinical routine.

Aiming at the limitations of clinical diagnosis of Parkinson's disease (PD) with rapid eye movement sleep behavior disorder (RBD), in order to improve the accuracy of diagnosis, an intelligent-aided diagnosis method based on few-channel electroencephalogram (EEG) and time-frequency deep network is proposed for PD with RBD. Firstly, in order to improve the speed of the operation and robustness of the algorithm, the 6-channel scalp EEG of each subject were segmented with the same time-window. Secondly, the model of time-frequency deep network was constructed and trained with time-window EEG data to obtain the segmentation-based classification result. Finally, the output of time-frequency deep network was postprocessed to obtain the subject-based diagnosis result. Polysomnography (PSG) of 60 patients, including 30 idiopathic PD and 30 PD with RBD, were collected by Nanjing Brain Hospital Affiliated to Nanjing Medical University and the doctor's detection results of PSG were taken as the gold standard in our study. The accuracy of the segmentation-based classification was 0.902 4 in the validation set. The accuracy of the subject-based classification was 0.933 3 in the test set. Compared with the RBD screening questionnaire (RBDSQ), the novel approach has clinical application value.
Electroencephalography ; Humans ; Intelligence ; Parkinson Disease/diagnosis* ; Polysomnography ; REM Sleep Behavior Disorder/diagnosis*

Objective:To investigate the distribution and clinical significance of subtypes of antimitochondrial antibodies (AMA)-M2, M4, M9 in primary biliary cholangitis (PBC).Methods:A total of 1 367 patients were detected with AMA-M2, M4, M9 in Peking Union Medical College Hospital (PUMCH) from Jan 2014 to Dec 2019 and the clinical parameters were collected. The distribution patterns of AMA subtypes in different groups were analyzed and the diagnostic sensitivity and specificity of AMA subtypes in PBC were calculated. Chi-square test was used for statistical analysis.Results:In 1 367 patients, 236 of whom were positive for AMA subtypes. The positivity of AMA subtypes in female was significantly higher than in male (20.34% vs 9.41%, χ2=23.792, P<0.01). In addition, the positivity of AMA subtypes was significantly higher in 30-65 years old patients than in patients younger than 30 years old or older than 65 years old [(20.00%(193/965) vs 10.97%(17/155) vs 10.53%(26/247), χ2=17.209, P<0.01]. 110 patients with positive AMA subtypes were diagnosed with PBC. The diagnostic sensitivity and specificity of AMA-M2 were both desirable [94.64%(106/112) and 92.35%(1 159/1 255)]. Although the specificity of AMA-M4 was as high as 99.12%(1 244/1 255), its sensitivity was very low [15.18%(17/122)]. Combined detection of different AMA subtypes could not improve the diagnostic sensitivity and specificity significantly. Diseases other than PBC can be positive for AMA subtypes, predominantly for AMA-M2. Conclusion:Female and 30-65 years old patients were more frequently positive for AMA subtypes. AMA-M2 was the most valuable AMA subtype for diagnosing PBC.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective:To study the effect of left atrioventricular interphase (LAVI) via esophageal electrocardiogram on cardiac function after dual-chamber pacemaker implantation in patients with high-degree atrioventricular block.Methods:Using a prospective approach, 40 patients with high-degree atrioventricular block who would undergo dual-chamber pacemaker implantation from January 2017 to March 2018 in Department of Cardiovascular Medicine, Dalian Municipal Central Hospital Affiliated of Dalian Medical University were enrolled. All patients accepted esophageal electrocardiogram tests at 3 months after the implantation, to exam the interatrial conduction time (IACT) of sinus rhythm and pacing rhythm, and interventricular conduction time (IVCT). Then based on the outcome of the echocardiography test, the optimal atrioventricular delay (AVD) of the pacemaker of each patient was determined while the LAVI differed from 100 ms to 150 ms. The left ventricular ejection fraction (LVEF), peak speed of blood flow velocity in early mitral orifice diastole (E), E peak deceleration time (EDT), peak speed of early mitral annular diastolic movement (e′), isovolumic relaxation time (IVRT) and left atrial volume (LAV) were tested by echocardiogram before implantation, before AVD adjustment at 3 months after implantation, after AVD adjustment at 3 months after implantation, and 6, 12, and 18 months after implantation. Then, the left atrial volume index (LAV/body surface area) and E/e′ were calculated.Results:Among the 40 patients, the IACT of sinus rhythm was (55.55 ± 10.33) ms, the IACT of pacing rhythm was (93.95 ± 12.77) ms, and the mean IVCT was (63.20 ± 17.84) ms; the optimal LAVI was 110 to 150 (132.00 ± 10.43) ms, and notably, the optimal LAVI between 120 and 140 ms was 82.5% (33/40). The LVEF, EDT, IVRT, left atrial volume index and E/e′ from before AVD adjustment of 3 months after implantation to follow-up endpoint (18 months after implantation) were significantly improved compared with those before implantation, and there were statistical differences ( P<0.01); the EDT and IVRT after AVD adjustment at 3 months after implantation were significantly improved than those before AVD adjustment at 3 months after implantation: (142.15 ± 35.58) ms vs. (125.94 ± 31.13) ms and (119.52 ± 22.15) ms vs. (133.92 ± 23.87) ms, and there were statistical differences ( P<0.05); the IVRT and left atrial volume index 18 months after implantation were significantly improved compared with those before AVD adjustment at 3 months after implantation: (122.07 ± 16.99) ms vs. (133.92 ± 23.87) and 32.94 ± 3.22 vs. 35.43 ± 5.76, and there were statistical differences ( P<0.05). Conclusions:Optimizing the LAVI after dual-chamber pacemaker implantation via esophageal electrocardiogram can improve the long-term prognosis of patients with high-degree atrioventricular block.

Objective:To explore the innovative measures of scientific and technological achievements transformation in hospital by taking the practical experience of scientific and technological achievements transformation of West China Hospital of Sichuan University (WCH).Methods:The data of patents and technological achievements transformation of WCH was analyzed.Results:WCH applied for 1 800 patents and granted 1 145 during January 2015 and December 2019. By 2019, the conversion rate of scientific and technological achievements of WCH reached 14%.Conclusions:WCH has achieved remarkable results in promoting the scientific and technological achievements transformation through a series of innovative explorations and practices, including building professional technology transfer organizations and teams, establishing achievement transformation incentive policies, developing technology transformation standard process and regulations, creating a positive atmosphere of achievement transformation , as well as actively cultivating high-value patents.

Objective:To establish a solvent desorption gas chromatography method for determination of cyclohexene in workplace air.Methods:Cyclohexene in the air of workplace was collected with carbon tube and desorbed by carbon disulfide. The target toxicant was separated with the GC column and analyzed with FID detector, identified by retention time, and quantified by peak area.Results:The linear range of cyclohexene in the air of workplace was 0.77~4 050.00 μg/ml, with a correlation coefficient of 0.9999. The limit of detection was 0.23 μg/ml. The lower limit of quantification was 0.77 μg/ml. The minimum detectable concentration was 0.15 mg/m 3 under1.5 L sampling volume and 1.0 ml extraction solution volume. The within-run precision of different cyclohexene concentrations was 0.62%~1.9% and the between-run precisions was 1.5%~3.5%; The average extraction efficiency was 96.4%; Penetration capacity (100 mg of carbon tube) was 29.4 mg; The average collection efficiency was 100%; The samples could be stored for 7 days at room temperature. When placed in 4 ℃ refrigerator, the samples could be stored for 14 days. The potential coexistence of cyclohexane, hexane, benzene, toluene and ethylbenzene with cyclohexene in the air did not interfere with the results of determination. Conclusion:This method has high sensitivity, precision, accuracy and lower limit of detection and it is applicable for determination of cyclohexene in workplace air.

Objective:To establish a solvent desorption gas chromatography method for determination of cyclohexene in workplace air.Methods:Cyclohexene in the air of workplace was collected with carbon tube and desorbed by carbon disulfide. The target toxicant was separated with the GC column and analyzed with FID detector, identified by retention time, and quantified by peak area.Results:The linear range of cyclohexene in the air of workplace was 0.77~4 050.00 μg/ml, with a correlation coefficient of 0.9999. The limit of detection was 0.23 μg/ml. The lower limit of quantification was 0.77 μg/ml. The minimum detectable concentration was 0.15 mg/m 3 under1.5 L sampling volume and 1.0 ml extraction solution volume. The within-run precision of different cyclohexene concentrations was 0.62%~1.9% and the between-run precisions was 1.5%~3.5%; The average extraction efficiency was 96.4%; Penetration capacity (100 mg of carbon tube) was 29.4 mg; The average collection efficiency was 100%; The samples could be stored for 7 days at room temperature. When placed in 4 ℃ refrigerator, the samples could be stored for 14 days. The potential coexistence of cyclohexane, hexane, benzene, toluene and ethylbenzene with cyclohexene in the air did not interfere with the results of determination. Conclusion:This method has high sensitivity, precision, accuracy and lower limit of detection and it is applicable for determination of cyclohexene in workplace air.