Volume 102 ·  Issue 37 ·  2022

With the in-depth research on treatment drugs of rheumatoid arthritis (RA), a variety of disease modifying anti-rheumatic drugs (DMARDs) have been approved for the treatment of RA. By now methotrexate (MTX) is still the anchor drug for RA treatment. The 2019 European League Against Rheumatism (EULAR) and 2021 American College of Rheumatology (ACR) recommendations for RA management both point out that for newly diagnosed RA patients, MTX monotherapy should be used as the first choice, which shows the importance of MTX monotherapy in DMARDs naïve RA. This paper mainly reviews the relevant researches on MTX in the treatment of RA in recent years, especially the relevant literature on the use of MTX monotherapy in initial treatment of RA. We summarize the development history, efficacy, treatment and adverse reactions of MTX to recognize the importance of MTX in the treatment of RA and the feasibility of MTX monotherapy.

The diagnosis and treatment of vascular diseases has experienced the era of open surgery and endovascular minimally invasive surgery. With the breakthrough of endovascular interventional robot, the rapid development of digitalization and informatization and the application of artificial intelligence, it will enter the era of precise, intelligent and minimally invasive surgery. This paper describes and provides new insights into the blueprint of diagnosis and treatment for vascular diseases in such era including three aspects: diagnosis and evaluation, endovascular treatment and postoperative treatment as well as follow-up.

Cognitive training, especially computer-aided cognitive training, as a non-drug intervention without obvious adverse reactions, has become an important means of prevention and intervention of cognitive impairment diseases. This guide systematically retrieves and evaluates the validity evidence involved in issues such as suitable objects and cognitive training methods, and recommends corresponding cognitive training programs for different patients and degrees of cognitive impairment. According to the needs, this guide suggests that objective and appropriate methods such as neuropsychological assessment and neuroplasticity index should be used to monitor the cognitive training process and comprehensively evaluate the efficacy of cognitive training. In order to further promote the application of cognitive training, this guide also recommends the method of setting up cognitive training center.

To compare the clinical outcomes of staged total knee arthroplasty (TKA) performed on both knees in the same patient using gap balancing (GB) and measured resection (MR) techniques, respectively.

The clinical data of 57 patients undergoing bilateral staged TKA at the Xi′an Jiaotong University Affiliated Honghui Hospital from July 2018 to January 2020 were analyzed. Using the random number table, MR or GB technique was selected when patients underwent primary TKA, and contralateral procedure was done with another technique. The procedures were performed by one chief surgeon, and the same prosthesis was chosen for all the procedures. The two osteotomy techniques for TKA were compared in terms of surgical status, radiographic data, functional recovery and satisfaction rate.

Total of 57 patients, including 16 males and 41 females, were included in the study with a mean age of (68.5±4.6) years (59-79 years) at primary TKA. All patients were followed up for (29.6±4.5) months (22-39 months). The interval between the two procedures was (4.7±3.0) months (0.5-12.0 months). Postoperative drainage was less in the GB side when compared with that in the MR side [(93.6±22.2) ml vs (109.9±36.9) ml, P=0.003]. At the 1-month postoperative follow-up, the visual analogue scale (VAS) of pain was lower on the GB side (3.0±0.8) than on the MR side (3.5±1.2), the range of motion (ROM) was higher on the GB side (105.7°±8.2° vs 100.2°±7.5°), the Knee Society Score (KSS) was higher on the GB side (78.5±5.4 vs 74.2±6.3), and the Western Ontario and McMaster University (WOMAC) score was lower on the GB side (35.4±5.5 vs 38.0±6.3), there were significant differences in the up-mentioned indexes between the two groups (all P<0.05). However, the repeated-measures analysis of variance indicated that there was no significant difference in VAS score, ROM, KSS score and WOMAC score between the two techniques (all P>0.05). The satisfactory rate of GB technique was 84.2%(48/57), ant it was 86.0%(49/57) with MR technique (P=0.446). There was also no significant difference between the two techniques in terms of complications (P=0.754).

Both the GB and MR technique result in good knee function with similar clinical outcomes in patients receiving TKA in both knees for osteoarthritis without significant deformity.

To explore the clinical characteristics, the correlation between lactate, procalcitonin and disease severity of imported malaria from Africa.

The clinical data of 186 patients with imported malaria were collected from January 1, 2018 to April 30, 2021 in the Guangzhou Eighth People′s Hospital, Guangzhou Medical University. The general conditions, clinical symptoms, laboratory tests, treatment, and prognosis of the patients were analyzed retrospectively. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of relevant indicators in predicting severe malaria.

A total of 186 patients were divided into severe cases (n=48) and non-severe cases (n=138) in this study, of which the mean age was (38.3±10.3) years, 169(90.9%) cases were male, 17(9.1%) cases were female. The main infection species was Plasmodium falciparum, in a total of 166 cases (89.2%). The severe cases were all falciparum malarias. Compared with the non-severe group, the lactic, procalcitonin, white blood cell count and neutrophil count of the severe group were all increased, the differences were all statistically significant (all P<0.01); the percentage of monocytes, red blood cell count, hemoglobin, hematocrit and platelet count were all decreased, the difference were all statistically significant (all P<0.01). The areas under the ROC curves (AUC)(95%CI) of lactate, procalcitonin, red blood cell count, hemoglobin, hematocrit and platelet count for predicting severe malaria was 0.753(0.663-0.844), 0.755(0.670-0.841), 0.782(0.700-0.864), 0.738(0.652-0.823), 0.760(0.676-0.844), 0.778(0.699-0.857), respectively (all P<0.01). When the Youden indexes were at their maximum, the best cut-off value of lactic was 2.29 mmol/L, with sensitivity in predicting of severe malaria was 56.3%, and the specificity was 93.5%; the best cut-off value of procalcitonin was 2.12 μg/L, with sensitivity in predicting of severe malaria was 77.1%, and the specificity was 68.1%. The fatality rate of severe malaria was 4.2% (2/48).

Anemia and thrombocytopenia are common indicators for predicting the severity of malaria. Lactic and procalcitonin also have higher predictive value for severe malaria, which could help to identify severe malaria as early as possible, improve the cure rate and reduce the risk of death.

To identify the risk factors of pain after CT-guided preoperative localization of pulmonary nodules with 4-hook needle.

The clinical data of 212 patients, who underwent CT-guided preoperative localization of single pulmonary nodule with 4-hook needle in Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School from September 2021 to February 2022 were retrospectively analyzed. All patients, including 83 males and 129 females with an age of (54±12) years, were divided into mild pain group (n=163) and moderate-severe pain group (n=49) according to numeric rating scale (NRS) for assessment of pain intensity. The gender, age, body mass index, smoking history, American Society of Anesthesiologists physical status (ASA), nodule location, nodule size, nodule distance from pleura, needle tip distance from pleura, localization-related complications (pneumothorax, pulmonary hemorrhage) and NRS for assessment of pain intensity after pulmonary nodules localization were collected and compared between the two groups. Univariate analysis and multivariate binary logistic regression analysis were performed to identify the risk factors of moderate-severe pain after CT-guided preoperative localization of pulmonary nodules with 4-hook needle.

The success rate of preoperative localization was 100%. The rates of pneumothorax and pulmonary hemorrhage were 22.6% and 17.0%, respectively. Univariate analysis showed that there was no significant difference in gender, age, body mass index, smoking history, ASA physical status, nodule location, nodule size, nodule distance from pleura and localization-related complications (pneumothorax, pulmonary hemorrhage) between the two groups (P>0.05), while needle tip distance from pleura of moderate-severe pain group was significantly less than that of mild pain group [7(6, 11) mm vs 15(12, 19) mm, P<0.001]. Multivariate binary logistic regression analysis showed that needle tip distance from pleura was the only risk factor for moderate-severe pain (OR=0.645, 95%CI: 0.562-0.739, P<0.001). According to receiver operating characteristic (ROC) curve analysis, when the cut-off value of needle tip distance from pleura was 9.5 mm, the sensitivity was 69.4%(34/49), the specificity was 90.2%(147/163), and the area under the curve (AUC) was 0.878 (95%CI: 0.820-0.935, P<0.001).

Needle tip distance from pleura was the independent risk factor of moderate-severe pain after CT-guided preoperative localization of pulmonary nodules with 4-hook needle. The less needle tip distance from pleura is, the higher risk of moderate-severe pain occurs.

To compare the efficacy of preprotein convertase subtilisin lysozyme 9 (PCSK9) inhibitors with statins in patients with type 2 diabetes mellitus (T2DM).

A total of 140 patients with T2DM (80 males and 60 females) in the People′s Hospital Affiliated to Shandong First Medical University from January 2018 to January 2021 were selected, with a mean age of (55±5) years (41-72 years). The patients were divided into observation group (n=68) and control group (n=72) by the random number table method. Both groups were given conventional treatments such as hypoglycemic drugs, the control group was given statins to regulate lipids, and the observation group was given PCSK9 inhibitors to lower lipids. The differences of low-density lipoprotein cholesterol (LDL-C), interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) expression levels and standard-reaching rate of LDL-C between the two groups were compared. The correlation between serum PCSK9 level and fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other indicators in T2DM patients was analyzed by Pearson correlation analysis.

After treatment, the LDL-C of the observation group was (2.3±0.7) mmol/L, which was lower than that of the control group [(2.7±0.7) mmol/L] (P=0.024); the standard-reaching rate of LDL-C of the observation group was 89.7% (61/68), which was higher than that of the control group [68.1% (49/72)] (P=0.002); the levels of IL-1, IL-6, TNF-, CRP, IL-10 and IL-8 in the observation group after treatment were (27.6±6.6) ng/L, (36.7±6.9) ng/L, (40.1±8.9) ng/L, (7.8±1.8) ng/L, (19.2±3.3) ng/L, (13.7±3.3) ng/L, respectively, which were lower than those in the control group [(30.6±7.9) ng/L, (40.1±7.3) ng/L, (43.4±9.2) ng/L, (10.4±2.5) ng/L, (30.7±3.7) ng/L, (26.8±3.4) ng/L, respectively] (all P<0.05). After treatment, the PCSK9 level in the observation group was (74±13) μg/L, which was lower than that in the control group [(97±14) μg/L] (P<0.001). The level of PCSK9 in T2DM patients was positively correlated with LDL-C, IL-1, IL-6 and TNF-α (r=0.390, 0.433, 0.398 and 0.562, all P<0.05).

PCSK9 inhibitors have better lipid-regulating effects in patients with T2DM and can improve the level of inflammation at the same time.

To explore the related factors of internal border-zone (IBZ) infarcts in patients with symptomatic chronic internal carotid artery occlusion (CICAO).

From January 2011 to May 2019, the symptomatic CICAO patients in the Second Affiliated Hospital of Soochow University and the Ninth People′s Hospital of Suzhou were retrospectively analyzed. The patients were divided into IBZ group and non-IBZ group. The demographic data, laboratory examination and imaging data of the two groups were collected. Binary logistic regression analysis was used to identify the related factors of IBZ infarcts in patients with symptomatic CICAO.

A total of 185 patients (147 males and 38 females) were finally enrolled, with a mean age of (65±11) years old. There were 64 and 121 cases in IBZ group and non-IBZ group, respectively. The ratio of patients with ophthalmic artery (OA) reflux in IBZ group was 64.1% (41/64), which was significantly higher than that in non IBZ group [47.8% (55/121), P=0.037], while the ratio of patients with collateral compensation (ASTIN/SIR 3-4) in non-IBZ group was 66.1% (80/121), which was significantly higher than that in IBZ group [29.7% (19/64), P<0.001]. Multivariate logistic regression analysis showed that history of cerebral infarction (OR=2.233, 95%CI: 1.023-4.874), low density lipoprotein (LDL) (OR=1.516, 95%CI: 1.006-2.285) and OA reflux (OR=5.060, 95%CI: 1.160-22.081) were independent risk factors for IBZ infarcts in patients with symptomatic CICAO (all P<0.05); while prothrombin international normalized ratio (INR) (OR=0.010, 95%CI: 0.000-0.970) and collateral compensation (ASTIN/SIR 3-4) (OR=0.172, 95%CI: 0.079-0.373) were protective factors (all P<0.05).

OA reflux, LDL, and history of cerebral infarction are independent risk factors for IBZ infarcts in patients with symptomatic CICAO, while INR and collateral compensation scores (ASTIN/SIR 3-4) are the protective factors.

To explore the value of a nomogram based on clinical data and enhanced CT radiomics in the prediction of Epstein-Barr virus-associated gastric carcinoma(EBVaGC).

The data of 136 patients, including 100 males and 36 females, aged [M (Q₁, Q₃)] 65 (53, 71) years, with gastric cancer confirmed by surgery and pathology were retrospectively analyzed. According to Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization, those patients were divided into Epstein-Barr virus (EBV) positive group (n=32) and EBV negative group (n=104). All patients underwent multi-phase enhanced CT scanning before surgery and randomly assigned to the training group (n=95) and validation group (n=41) in a ratio of 7︰3. MaZda software was used to extract radiomics features of enhanced CT images. The intra-group correlation coefficient (ICC), variance analysis and minimum absolute shrinkage and selection algorithm (LASSO) regression were used to reduce the dimensionality of the radiomics features, and then the radiomics score (Radscore) was calculated. The nomogram model was based on combined clinical data, morphological features and Radscore. The predictive power of the nomogram was evaluated according to the area under the receiver operating characteristic curve (AUC), and the net clinical benefit of the nomogram was evaluated by the decision curve and calibration curves were drawn according to the data of the training group and the validation group to analyze the consistency of the nomogram model.

After selection, six optimal radiomics features were obtained, including Mean, Skewness, S(1, 0) Sum entropy, S(1, 1) Contrast, 99% percentile and S(2, 2)Angular second moment. Radscore of EBV positive group were higher than that of the EBV negative group (training group: 3.78±0.83 vs 2.80±0.98; validation group: 3.81±0.47 vs 2.94±0.95) (both P<0.05) both in the training group and validation group. The AUC of the radiomics model in training group and validation group were 0.773(95%CI:0.612-0.962)and 0.792(95%CI:0.597-0.927)respectively,and the sensitivity and specificity were 63.6% and 93.1%, 70.0% and 87.1%, respectively. The AUC of the nomogram model based on clinical data and radiomics in the training group and the validation group were 0.883(95%CI:0.644-0.984) and 0.851(95%CI:0.715-0.996), respectively. The nomogram model showed superior predictive performance (both P<0.05).

The nomogram model based on clinical data and radiomics has better efficacy in the prediction of Epstein-Barr virus associated gastric cancer.

To explore the application value of cardiac magnetic resonance (CMR) native T₁ mapping for risk stratification in patients with pulmonary arterial hypertension (PAH).

A total of 59 patients with diagnosed PAH and clear-documented risk status in Peking Union Medical College Hospital and underwent CMR examination between January 2019 and December 2021 were retrospectively included, which including 12 males and 47 females, aged from 4 to 77 (31±13) years. Those patients were subdivided into two groups based on the clinically-assessed risk status: low-risk group (n=30) and intermediate-/high-risk group (n=29). Twenty-five healthy individuals were included as controls. Base, midventricular, and apical inferior right ventricular insertion point (IRVIP) native T₁ values on short axis images were measured. Native T1 values in PAH patients and control group, in low-risk group and intermediate-/high-risk group were compared, respectively, and receiver operating characteristics (ROC) curves with area under the curves (AUC) were calculated to evaluate the application value of native T₁ values for risk stratification in PAH patients.

Base, midventricular and apical IRVIP native T₁ of PAH patients were all significantly increased as compared to controls [Base:(1 439.31±129.96) vs (1 282.36±37.18) ms;midventricular:(1 450.32±111.55) vs (1 287.56±53.16) ms;apical:(1 444.12±109.15) vs (1 266.36±75.31) ms](all P<0.001). The midventricular IRVIP native T₁ values were significantly higher in patients in intermediate-/high-risk status as compared to those in low-risk status [ (1 493.24±126.32) vs (1 428.50±85.73) ms,P=0.026]. The AUC of mid ventricle IRVIP native T₁ for distinguishing patients in intermediate-/high-risk status was 0.741. The base [(1 458.21±134.96) vs (1 421.03±104.75) ms, P=0.241] and apical [(1 465.90±125.36) vs (1 423.07±87.87) ms,P=0.136] IRVIP native T1 values in patients in intermediate-/high-risk group were also numerically higher as compared with patients in low-risk status, however, without statistical significant (both P>0.05).

Midventricular IRVIP native T₁ value might have a role for assisting in risk stratification in PAH patients, which was clinically significant for facilitating the work-up and prognosis improvement of PAH patients.

To investigate the analytical performance verification protocols and performance specifications of platelet-dependent von Willebrand factor (VWF) activity testing (VWF:GPIbM) for clinical laboratories.

According to Clinical Laboratory Standards Institute (CLSI) documents and National Health Standard of China, the performance verification of VWF:GPIbM was designed and implemented using Sysmex CS-5100 instrument and its corresponding reagents. (1) Precision verification: Two commercial quality control samples (with normal and low activity levels) and three plasma pools (with activity range from 5.0% to 150.0%) were prepared. Each sample was tested five times daily for five consecutive days. The coefficient of variation (CV) of intra-and inter-run precisions were calculated, and the precision evaluation criterion was set according to package inserts. (2) Trueness verification: The calibrator was diluted to five reference materials with activity values of 5.2%, 31.2%, 62.4%, 104.0% and 138.7%, and each reference material was tested five times daily for five consecutive days. The bias between the measured value and the reference value was calculated, and the trueness evaluation criterion was set according to the total allowable error. (3) Linearity verification: Ten pooled plasmas with theoretical value range from 3.6% to 160.4% were prepared for the linearity verification of two calibration curves set by the manufacturer (i.e. low range and normal range calibration curve). Each pooled plasma was tested three times in a single run. The slope and R² of linear regression of mean of measured value and theoretical value, as well as bias, were calculated, and the linearity evaluation criterion was set according to National Health Standard of China and package inserts. (4) Limit of quantitation verification: The calibrator was diluted to two reference materials with activity values of 3.3% and 2.7%, and each material was tested twelve times. The limit of quantitation evaluation criterion was set according to CLSI document.

The CVs of intra-and inter-run were 1.0%-2.5% and 1.1%-2.6%, respectively. The biases of trueness verification were -0.4%, 1.0%, -2.6%, 0.3% and -2.7%, respectively. The linearity verification results of low range (3.6%-31.8%) and normal range (28.4%-160.4%) showed that the slopes of regression equation were 1.021 7 and 0.996 2, respectively, R² were 0.993 5 and 0.993 9, respectively, and the biases with 0-1.8% and -10.1%-0 of plasmas met the criterion. The biases ranged from -0.4% to 0.3% of test results in the verification of limit of quantitation met the criterion.

The verification results of VWF:GPIbM assay for precision, trueness, linearity and limit of quantification meet the performance requirements indicated in the package inserts and the criteria set in this study, which can be taken as a reference of performance verification for the clinical laboratories.

Data of 42 patients with carotid web diagnosed by ultrasound or confirmed by computed tomography angiography (CTA) or surgical pathology in the First Affiliated Hospital of Zhengzhou University were retrospectively collected, including 20 males and 22 females, aged 35-77 (55±11) years. According to the accuracy of ultrasound diagnosis of carotid web, the patients were divided into Group of misdiagnoses by ultrasonoscopy (MD group, 10 cases) and Group of correct diagnosis by ultrasonoscopy (CD group, 32 cases). Compared with CD group, carotid webs in MD group were more likely to be associated with plaque (100.00% vs 12.50%), severe local vascular stenosis (70.00% vs 0) or occlusion (30.00% vs 0) (all P<0.05), carotid intima-media thickening (80.00% vs 28.13%) and plaque formation in other parts of carotid artery (100.00% vs 37.50%) (both P<0.05). Moreover, the correct diagnosis rate of ultrasound was higher than that of CTA (76.19% vs 59.52%, P=0.039).

Female patient, previously diagnosed with multiple sclerosis for 12 years, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis for 1 year, cured, discontinued immunization 2 weeks before onset. The patient had headache and abnormal vision, manifested as vision deformation and trembling sensation. Physical examination: Thick nystagmus can be seen when both eyes look to the right side, and subtle nystagmus can be seen when looking to the left side. After completing serum antibody and cerebrospinal fluid examination, enhanced magnetic resonance imaging of head and spinal cord, it was diagnosed as anti-myelin oligodendrocyte glycoprotein immunoglobulin G antibody-related disease. Combined with previous medical history, it was diagnosed as overlapping syndrome co-existing with anti-NMDAR encephalitis. The patient received intravenous glucocorticoid shock, intravenous human immunoglobulin, oral mycophenolate mofetil and other treatments, and his symptoms and signs improved significantly. Follow-up for more than 3 years, rituximab treatment every six months, no recurrence of the disease.

Intracranial atherosclerotic stenosis is the cause of ischemic stroke with high incidence in Asian population, and the proportion can be as high as 46.6%. In western countries, the proportion is only 10% to 15%. Endovascular therapy such as interventional stenting has been regarded as a potential treatment for intracranial atherosclerotic stenosis. The SAMMPRIS and VISSIT studies are the only two multicenter randomized controlled studies comparing stents with drug alone in the world, both mainly in the Western population. The results show that stent therapy has a higher complication rate, which is worse than drug therapy alone. In recent years, many prospective registry studies and real-world studies at home and abroad have shown that the risk of intracranial arterial stent complications is only 2.0% ~4.3%, which is in sharp contrast with the 14.7% in the SAMMPRIS study. Therefore, therapeutic strategies for intracranial atherosclerotic stenosis are controversial.