Effect and mechanism of recombinant human fibroblast growth factor 18 on osteoporosis in OVX mice.

OBJECTIVES: This study aimed to investigate the effect and the mechanism of recombinant human fibroblast growth factor 18 (rhFGF18) on postmenopausal osteoporosis. METHODS: The effect of rhFGF18 on the proliferation and apoptosis of osteoblasts and the mechanism underlying such an effect was evaluated using an oxidative stress model of the MC3T3-E1 cell line. Furthermore, ovariectomy was performed on ICR mice to imitate estrogen-deficiency postmenopausal osteoporosis. Bone metabolism and bone morphological parameters in the ovariectomized (OVX) mice were evaluated. RESULTS: The results obtained from the cell model showed that FGF18 promoted MC3T3-E1 cell proliferation by activating the extracellular signal-regulated kinase (ERK) and p38 instead of c-Jun N-terminal kinase (JNK). FGF18 also prevented cells from damage inflicted by oxidative stress via inhibition of apoptosis. After FGF18 administration, the expression level of anti-apoptotic protein Bcl-2 in the mice was upregulated, whereas those of the pro-apoptotic proteins Bax and caspase-3 were downregulated. Administering FGF18 also improved bone metabolism and bone morphological parameters in OVX mice. CONCLUSIONS: FGF18 could effectively prevent bone loss in OVX mice by enhancing osteoblastogenesis and protecting osteoblasts from oxidative stress-induced apoptosis.

[SRF-rearranged cellular perivascular myoid tumor: a clinicopathological analysis of two cases].

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor. Methods: Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed. Results: Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively. Conclusions: SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Using CT imaging features to predict visceral pleural invasion of non-small-cell lung cancer.

AIM: To examine the diagnostic performance of different models based on computed tomography (CT) imaging features in differentiating the invasiveness of non-small-cell lung cancer (NSCLC) with multiple pleural contact types. MATERIALS AND METHODS: A total of 1,573 patients with NSCLC (tumour size ≤3 cm) were included retrospectively. The clinical and pathological data and preoperative imaging features of these patients were investigated and their relationships with visceral pleural invasion (VPI) were compared statistically. Multivariate logistic regression was used to eliminate confounding factors and establish different predictive models. RESULTS: By univariate analysis and multivariable adjustment, surgical history, tumour marker (TM), number of pleural tags, length of solid contact and obstructive inflammation were identified as independent risk predictors of pleural invasiveness (p=0.014, 0.003, <0.001, <0.001, and 0.017, respectively). In the training group, comparison of the diagnostic efficacy between the combined model including these five independent predictors and the image feature model involving the latter three imaging predictors were as follows: sensitivity of 88.9% versus 77% and specificity of 73.5% versus 84.1%, with AUC of 0.868 (95% CI: 0.848-0.886) versus 0.862 (95% CI: 0.842-0.880; p=0.377). In the validation group, the sensitivity and specificity of these two models were as follow: the combined model, 93.5% and 74.3%, the imaging feature model, 77.4% and 81.3%, and their areas under the curve (AUCs) were both 0.884 (95% CI: 0.842-0.919). The best cut-off value of length of solid contact was 7.5 mm (sensitivity 68.9%, specificity 75.5%). CONCLUSIONS: The image feature model showed great potential in predicting pleural invasiveness, and had comparable diagnostic efficacy compared with the combined model containing clinical data.

The performance of left/right adrenal volume ratio and volume difference in predicting unilateral primary aldosteronism.

PURPOSE: The role of computed tomography (CT) in the diagnosis of primary aldosteronism (PA) warrants attention, since the success application of adrenal venous sampling (AVS) remains limited. We aimed to investigate the value of CT-based volumetric indicators, including left-versus-right-adrenal-volume ratio (L/Rv) and left-subtract-right-adrenal-volume difference (L - Rv), in the diagnosis of unilateral primary aldosteronism (UPA). METHODS: A retrospective case-control study included 153 patients with PA and 1272 controls. AVS was used to classify patients into bilateral disease, left-sided disease, and right-sided disease groups. RESULTS: Adrenal gland volume on both sides of PA patients was significantly larger than controls. The optimal cutoff values of L/Rv and L - Rv were 1.417 [area under the curve (AUC) 0.864] and 1.185 (AUC 0.827), respectively, for the diagnosis of left-sided PA, and 1.030 (AUC 0.767) and 0.220 (AUC 0.769), respectively, for the diagnosis of right-sided PA. The mean AUC for subsequent cross-validation ranged from 0.77 ± 0.03 to 0.86 ± 0.02. Based on the optimal cutoff values, the combination of L/Rv and L - Rv detected 69.6% of patients with left-sided PA and 74.3% of patients with right-sided PA, with a specificity of 93.5% and 89.0%, respectively. For a better clinical application, we reported the sub-optimal cutoffs corresponding to a specificity of 95%. A L/Rv higher than 1.431 and a L - Rv higher than 3.185 as sub-optimal cutoff values was detected in 26.1% of patients with left-sided PA (specificity: 97.2%). A L/Rv smaller than 0.892 and a L - Rv smaller than -0.640 could detect 48.6% of patients with right-sided PA (specificity: 97.5%). CONCLUSIONS: CT-based L/Rv and L - Rv performed well in predicting UPA. The combination of L/Rv and L - Rv may serve as a potential indicator for guiding surgical decision making in centers without AVS programs.

[Efficacy and safety of modified Hartel approach in the treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation].

Objective: To assess the efficacy and safety of modified Hartel approach in the treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation. Methods: A total of 89 patients with primary trigeminal neuralgia in Nanjing Drum Tower Clinical College of Xuzhou Medical University from July 2021 to July 2022 were prospectively included, and were divided into experimental group (n=45, modified Hartel approach: selecting 2.0 cm lateral to and 1.0 cm below angulus oris as insertion point) and control group (n=44, traditional Hartel approach: selecting 2.5 cm lateral to the angulus oris as insertion point) according to the random number table method. There were 19 males and 26 females in the experimental group, and aged (67.6±8.8) years. Meanwhile, there were 19 males and 25 females in the control group, and aged (64.8±11.7) years. All the patients were treated by CT-guided radiofrequency thermocoagulation. The success rate of one-time puncture, number of punctures, the time of puncture, operation time, numerical rating scale (NRS) scores and complications were recorded and compared between the two groups. Results: The success rate of one-time puncture in experimental group was 64.4% (29/45), which was higher than that in control group 31.8% (14/44) (P<0.05). The number of punctures [M (Q1, Q3)], the time of puncture [M (Q1, Q3)] and operation time in the experimental group were 1 (1, 2), 218 (206, 378) s, (19.9±2.7) min, which were less than those of control group [2 (1, 3), 390 (231, 598) s, (27.0±3.9) min] (all P<0.05). The NRS scores [M (Q1, Q3)] of 1 day, 1 month and 3 months after surgery in the experimental group were 1 (1, 2), 1 (0, 2) and 1(0, 1), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). The NRS scores [M (Q1, Q3)] of 1 day, 1 month and 3 months after surgery in the control group were 1 (1, 2), 1 (0, 2) and 1 (0, 2), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). There was no statistically significant difference in the incidence of nausea and vomiting, facial numbness, and decreased masticatory muscle strength between the two groups (all P>0.05) In the experimental group, two patients had puncture needles into the oral cavity, with timely detection and replacement of puncture needles, and no infection occurred. There was no cerebrospinal fluid leakage and decreased corneal reflex in both groups. Conclusion: The modified Hartel approach can significantly improve the success rate of one-time puncture via foramen ovale, reduce the operation time and the incidence of postoperative facial swelling, which is a safe and effective puncture method.

[Review and perspective of clinical research involving chest tightness variant asthma in China].

Chest tightness variant asthma (CTVA) was first reported and named by Chinese scholars in 2013. It is a new clinical type of asthma characterized by chest tightness as the only or primary symptom, without typical asthma manifestations such as recurrent wheezing and shortness of breath, and without wheezing sounds heard during lung auscultation. The overall epidemiological data on CTVA is currently unavailable. Its pathogenesis is similar to that of typical asthma, involving eosinophilic airway inflammation. Due to the lack of typical clinical manifestations, insufficient knowledge of this disease in some clinicians and some other reasons, CTVA is susceptible to misdiagnosis or missed diagnosis. Currently, the diagnostic criteria for CTVA are: chest tightness as the only or primary symptom, without typical asthma symptoms and signs such as wheezing and shortness of breath, and with any one of the objective indicators of variable airflow limitation. Effective anti-asthma treatment is required, and other diseases that cause chest tightness, such as cardiovascular, digestive, nervous, muscular, and mental diseases should be excluded. CTVA treatment follows that of typical asthma, but the specific treatment duration is uncertain and may require long-term management. Traditional Chinese medicine has shown some therapeutic effects on CTVA. Most CTVA patients have a good prognosis after active anti-asthma treatment. This paper analyzes and summarizes the research of CTVA in China from 2013 and provides new perspectives for further exploration of CTVA.

[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.

[Analysis of the development status and trend of vaccines in China's immunization program in the past decade].

Vaccines for immunization programs play a pivotal role in the prevention and control of infectious diseases in China. Since the implementation of the Expanded Program on Immunization in 2007, a total of 15 vaccines have been used in the national immunization program, which can prevent 15 kinds of diseases. The development of vaccines in China's immunization program in the past decade is analyzed in terms of variety, quantity, production enterprise, quality standard, and supervision system. The results show that the average dose of vaccines for China's immunization planning is about 570 million doses per year from 2011 to 2020. The overall development of the vaccine industry for immunization planning is stable, and there are between one to five manufacturers for each type of vaccine mainly relying on domestic production. Vaccine quality standards have been continuously improved and are basically consistent with international standards. The vaccine supervision system has been continuously completed and covered the entire process of research and development, production and distribution.

Association between bariatric surgery with long-term analgesic prescription and all-cause mortality among patients with osteoarthritis: a general population-based cohort study.

OBJECTIVES: There is still a large unmet need for novel osteoarthritis (OA) treatments that could provide clinically important effects on long-term pain relief (≥12 months). We examined the relation of bariatric surgery along with weight loss to analgesic prescription and all-cause mortality among individuals with OA. METHODS: We conducted a cohort study among individuals with OA using The Health Improvement Network. We compared the rate of no analgesic prescription ≥12 consecutive months and the risk of all-cause mortality using inverse probability weighting Cox-proportional hazard models and the difference in number of analgesic prescriptions (non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in the 50th, 75th and 90th percentiles using quantile regression model between bariatric and non-bariatric cohorts. RESULTS: Included were 588,494 individuals (694 had bariatric surgery). Compared with non-bariatric group, the rate of no analgesic prescription ≥12 consecutive months was higher (HR = 1.23, 95% CI: 1.08-1.38) in bariatric surgery group, and the number of analgesic prescriptions was lower in the 75th (44 vs 58) and 90th (74 vs 106) percentiles during a mean follow-up of 4.3 years. All-cause mortality in bariatric surgery group was lower than comparison group (HR = 0.46, 95% CI: 0.41-0.51). CONCLUSION: This study presents the first evidence that bariatric surgery was associated with decreased long-term analgesic prescription and decreased all-cause mortality among individuals with OA. However, our findings may be overestimated owing to intractable confounding by indication for bariatric surgery; thus, future studies (e.g., clinical trials) are warranted.

Adrenal metastases: early biphasic contrast-enhanced CT findings with emphasis on differentiation from lipid-poor adrenal adenomas.

AIM: To evaluate the accuracy of unenhanced attenuation and early biphasic contrast-enhanced computed tomography (CT) in differentiating adrenal metastases (AMs) from lipid-poor adrenal adenomas (AAs). MATERIALS AND METHODS: This retrospective study included 37 patients with 50 AMs and 86 patients with 89 lipid-poor AAs. Quantitative data including the longest diameter (LD), the shortest diameter (SD), LD/SD ratio, CT attenuation values (CTu, CTa, CTv), degree of enhancement (DEAP, DEPP, DEpeak, APW, RPW), and peak enhanced/unenhanced (PE/U) CT attenuation ratio were obtained. Qualitative data including enhancement pattern, location, shape, the presence of calcification or haemorrhage, and intra-lesion necrosis were analysed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also calculated. RESULTS: The PE/U ratio (≤1.25), CTu (≥32.2 HU), DEpeak (≤43.15 HU), DEPP (≤37.65 HU), presence of intralesional necrosis, location (bilateral adrenal glands), and irregular shape were significant variables for differentiating AMs from lipid-poor AAs (p<0.05). Among them, PE/U ratio (≤1.25) was of greater value in differentiating the two adrenal diseases, with sensitivity, specificity, area under the receiver operating curve (ROC) curve (AUC) of 92%, 84%, 0.933, respectively. When at least any three of above criteria were combined, the sensitivity, specificity, PPV, and NPV for diagnosing AMs were 88%, 93%, 88%, and 88%, respectively. CONCLUSIONS: These seven CT criteria are conducive to differentiate AMs from lipid-poor AAs. Early biphasic contrast-enhanced CT is a high-efficient and practical imaging tool in differentiating them.

[The predictive value of central venous-arterial CO2 difference/arterial-central venous O2 difference ratio for progressive organ dysfunction in patients with septic shock after resuscitation].

Objective: To study the predictive value of central venous-arterial CO2 difference (Pv-aCO2)/arterial-central venous O2 difference (Ca-vO2) ratio for progressive organ dysfunction in patients with septic shock after resuscitation. Methods: Septic shock patients receiving resuscitation in ICU were retrospectively enrolled from July 2018 to June 2019 at the First Affiliated Hospital Anhui Medical University. Hemodynamic and laboratory data were collected. Single and multivariate logistic regression model was constructed to explore the independent risk factors of progressive organ dysfunction. The predictive value of hemodynamic parameters to progression of organ dysfunction was determined using receiver operating characteristic (ROC)curve analysis. Results: A total of 99 patients were enrolled with 25 patients (25.25%) progressing to organ dysfunction. The norepinephrine dose [0.61 (0.27,1.42) µg·kg-1·min-1 vs. 0.91 (0.47,2.87) µg·kg-1·min-1], blood lactic acid [2.93 (1.77,5.88) mmol/L vs. 6.15 (2.56,8.59) mmol/L], Pv-aCO2 [5.00 (3.98,7.85) mmHg(1 mmHg=0.133 kPa) vs. 7.00 (5.00,8.35) mmHg] and Pv-aCO2/Ca-vO2 [1.36(1.17,1.69) vs. 2.23 (1.83,2.78)] in patients with progressive organ dysfunction were significantly higher than those in patients without(P<0.05). Multivariate logistic regression analysis suggested that Pv-aCO2/Ca-vO2 (OR=20.48,95%CI 5.25-79.93,P<0.001) was independent risk factors for predicting organ dysfunction. The cutoff value of Pv-aCO2/Ca-vO2 was equal or more than 1.77 with a sensitivity of 80.00% and a specificity of 79.73%. Compared with those with Pv-aCO2/Ca-vO2<1.77, patients with Pv-aCO2/Ca-vO2≥1.77 had a greater probability of progressive organ dysfunction (47.37% vs. 8.20%, P<0.001). Conclusion: The progression of organ dysfunction in septic patients after resuscitation is associated with poor prognosis. Pv-aCO2/Ca-vO2 is a good indicator to evaluate oxygen metabolism and predict the progression of organ dysfunction.

[Application of 3D-printed navigation plate in pulsed radiofrequency therapy of dorsal root ganglion in thoracic postherpetic neuralgia].

Objective: To evaluate the accuracy, efficacy and safety of 3D-printed personalized navigation template in the treatment of thoracic postherpetic neuralgia (PHN) with dorsal root ganglion pulsed radiofrequency (DRG-PRF). Methods: A total of 63 patients with thoracic PHN from March 2019 to December 2020 in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were enrolled and randomly divided into study group (n=31) and control group (n=32) by random number table method. The study group received DRG-PRF treatment assisted by 3D-printed navigation template, while the control group received DRG-PRF treatment guided by conventional CT. The one-time success rate of puncture, the incidence of puncture times ≥3, the number of punctures, puncture time, visual analogue scale (VAS) score and surgical complications between the two groups were compared. Results: The one-time success rate of puncture in study group was 84.9% (79/93), which was higher than that of control group [30.2% (29/96)] (P<0.001). The incidence of puncture times ≥3, the number of punctures, puncture time in study group were 4.3% (4/93), 1 (1, 1) and 2.9 (2.8, 3.0) min, respectively, which were lower than that of the control group [21.9% (21/96), 2(1, 3), 9.0 (4.5, 12.9) min, respectively] (all P<0.01). No difference was found in VAS score at each time point before and after surgery between the two groups (all P>0.05). There was one case of pleura puncture in the control group, but no other complications such as straying into vertebral canal, hematoma, spinal cord injury, limb movement disorder, infection were found in the two groups. Conclusions: 3D-printed personalized navigation template is an effective method to guide DRG-PRF for the treatment of thoracic postherpetic neuralgia. It can significantly improve the surgical efficiency of DRG-PRF, but has no significant effect on the surgical efficacy.

[Analysis on tissue-related biomarkers in patients with acute aortic dissection].

Objective: To explore the clinical implication of tissue-related biomarkers in patients with acute aortic dissection (AAD). Methods: It was a cross-sectional study. Ten Stanford Type A AAD patients, who were diagnosed and surgically treated in the Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, from December 2018 to August 2019, were selected as the case group. Meanwhile, 10 patients with atherosclerotic heart disease, who underwent coronary artery bypass grafting (CABG), were selected as control group. The ascending aorta tissue specimens from patients of the two groups were collected during the operation. Four-dimensional non-standard quantitative proteomics technology (4D-LFQ) was used to detect the protein profile of ascending aorta tissue specimens of the two groups and to screen out differentially expressed proteins and analyze their biological functions. Precise quantification of the selected target proteins was achieved by parallel response monitoring (PRM). Results: A total of 3 985 proteins were identified by 4D-LFQ technology, among which 3 350 proteins could be quantified. There were 39 proteins were significantly upregulated and 47 proteins were significantly downregulated in AAD group. The results of biological function analysis showed that most of the differentially expressed proteins were located in the extracellular, and their functions were mainly involved in cell migration and proliferation, inflammatory cell activation, cell contraction, and muscle organ development. The 15 selected proteins underwent precise quantification by PRM, and the results showed that integrin α-Ⅱb (ITGA2B), integrin α-M (ITGAM), integrin ß-2 (ITGB2), integrin ß-3 (ITGB3) were significantly upregulated in the ascending aorta tissue of AAD patients. Conclusion: ITGA2B, ITGAM, ITGB2, and ITGB3 are highly expressed in aortic tissues of patients with AAD, which may be used as biomarkers for the diagnosis of AAD patients.

[The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation].

Objective: To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Methods: This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke. Results: Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion: Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

[Association of Semaphorin 3A with thrombocytopenia in systemic lupus erythematosus].

OBJECTIVE: To measure the level of serum Semaphorin 3A (Sema3A) and to analyze the relationship between serum Sema3A and systemic lupus erythematosus (SLE) with thrombocytopenia. METHODS: The concentration of serum Sema3A was detected by enzyme-linked immuno sorbent assay (ELISA) in 170 SLE patients, 50 Sjögren's syndrome (SS) patients, 19 hypersplenism (HS) patients and 150 healthy controls (HC). Based on the presence of thrombocytopenia and whether the thrombocytopenia was in remission, the SLE patients were divided into three groups: SLE with thrombocytopenia (41 cases), SLE with thrombocytopenia remission (28 cases), and SLE without thrombocytopenia (101 cases). According to whether there was thrombocytopenia, the SS patients were divided into SS with thrombocytopenia (18 cases) and SS without thrombocytopenia (32 cases). The 28 SLE patients who underwent bone marrow aspiration biopsy were divided into two groups from the aspect of whether the bone marrow hyperplasia was normal (19 cases) or low (9 cases), as well as from the aspect of whether the maturity disturbance of megakaryocyte was positive (8 cases) or negative (20 cases). The serum Sema3A levels in SLE, SS, HS with HC were compared, meanwhile, the correlation between serum Sema3A level and platelet (PLT) in the patients with different diseases analyzed. RESULTS: (1) Serum Sema3A levels in SLE were significantly lower than in HC [(3.84±2.76) µg/L vs. (6.96±2.62) µg/L, P < 0.001], serum Sema3A levels in SS were also obviously lower than in HC [(4.35±3.57) µg/L vs. (6.96±2.62) µg/L, P < 0.001], and in HS it was lower than HC at a certain extant [(5.67±2.26) µg/L vs. (6.96±2.62) µg/L, P=0.041]. (2) Serum Sema3A levels in SLE were slightly lower than in SS, but there was no significant difference [(3.84±2.76) µg/L vs. (4.35±3.57) µg/L, P=0.282]. However, when compared with HS, serum Sema3A levels in SLE were significantly lower [(3.84±2.76) µg/L vs. (5.67±2.26) µg/L, P=0.006]. (3) Serum Sema3A concentration in SLE with thrombocytopenia was significantly lower than in SLE with thrombocytopenia remission [(1.28±1.06) µg/L vs. (3.83±2.65) µg/L, P < 0.001], and in SLE patients without thrombocytopenia [(1.28±1.06) µg/L vs. (4.87±2.60) µg/L, P < 0.001]. There was no significant difference between SLE with thrombocytopenia remission and SLE without thrombocytopenia [(3.83±2.65) µg/L vs. (4.87±2.600 µg/L, P=0.123]. Serum Sema3A concentration in SLE with thrombocytopenia was slightly lower than in SS with thrombocytopenia, but there was no significant difference [(1.28±1.06) µg/L vs. (1.68±1.11) µg/L, P=0.189]. (4) Strong positive correlations were found between serum Sema3A and PLT in SLE (r=0.600, P < 0.001). Positive correlations were also found between serum Sema3A and PLT in SS (r=0.573, P < 0.001). However, there was no such correlation showed in HS patients (P=0.393). (5) There was no significant difference of serum Sema3A concentration in SLE whether the bone marrow hyperplasia was normal or low. And the same situation appeared in the patients whether the maturity disturbance of megakaryocyte was positive or negative (P>0.05). CONCLUSION: Serum Sema3A was significantly reduced in SLE patients, and it was highly correlated with the blood damage. Similar conclusions could be drawn in patients with SS. The serum level of Sema3A was generally decreasing in desmosis which merged thrombocytopenia, and was obviously positive correlated with platelet counts.

[Clinical and immunological characteristics of myositis complicated with thromboembolism].

OBJECTIVE: To investigate and analyse the clinical and immunological features of patients with myositis complicated with thromboembolism. METHODS: We identified a cohort of 390 myositis patients diagnosed with myositis admitted to People's Hospital of Peking University from 2003 to 2019. The patients were retrospectively enrolled in this investigation. According to the outcome of the color Doppler ultrasound, CT pulmonary angiography, pulmonary ventilation and perfusion scan patients were divided into myositis with and without thromboembolism group. Demographic, clinical (heliotrope rash, Gottron's sign/papules, periungual erythema, skin ulceration, subcutaneous calcinosis, Mechanic's hands, myalgia, interstitial lung disease, pulmonary arterial hypertension), laboratory, immunological [anti-autoantibodies including melanoma differentiation associated gene 5 (anti-MDA5), anti-Mi-2, anti-transcription intermediary factor-1γ (anti-TIF-1γ, anti-nuclear matrix protein 2 (anti-NXP2), anti-small ubiquitin-like modifier activating enzyme (anti-SAE), anti-synthetase], imaging and therapeutic status data of the patients at the diagnosis of myositis with and without thromboembolism were collected and the differences in these data were analyzed. Logistic regressive analysis was used to identify the risk factors of thromboembolism. RESULTS: In the retrospective study, 390 myositis patients were investigated. The mean age of onset was (49.6±13.4) years, male to female ratio was 0.31 :1. Thromboembolism was identified in 4.62% (18/390) of the myositis patients, which was lower than the published reports. Out of 18 patients with thromboembolism, 55.6% (10/18) of them were deep venous thrombosis, followed by cerebral infarction (22.2%, 4/18), pulmonary embolism (11.1%, 2/18), renal artery embolism (5.6%, 1/18) and embolism of upper extremity (5.6%, 1/18). Fifty percent of thromboembolism events occurred 6 months after the diagnosis of myositis, 38.9% of thromboembolism events occurred 6 months within the diagnosis of myositis, 11.1% of thromboembolism events occurred 6 months before the diagnosis of myositis. As compared with the myositis patients without thromboembolism, the myositis patients complicated with thromboembolism were older [(58.3±11.7) years vs. (49.3±13.4) years, P=0.006]. C-reaction protein (CRP) (12.2 mg/L vs. 4.1 mg/L, P < 0.001), ferritin (20 085.5 µg/L vs. 216.6 µg/L, P < 0.001) and D-dimer (529.0 µg/L vs. 268.0 µg/L, P=0.002) were significantly higher in thromboembolism group. Diabetes (44.4% vs. 16.4%, P=0.006), coronary heart disease (22.2% vs. 3.0%, P=0.003) and surgery (16.7% vs. 3.5%, P=0.032) were observed more common in thromboembolism group than those without thromboembolism. Activated partial thromboplastin time (APTT) (26.9 s vs. 28.7 s, P=0.049) and albumin (32.4 g/L vs. 36.5 g/L, P=0.002) was lower in thromboembolism group. The risk factors of thromboembolism in the myositis patients were low level of albumin (OR=0.831, 95%CI: 0.736-0.939, P=0.003), diabetes (OR=4.468, 95%CI: 1.382-14.448, P=0.012), and coronary heart disease (OR=22.079, 95%CI: 3.589-135.837, P=0.001) were independent significant risk factors for thromboembolism in the patients with myositis. There was no significant difference in clinical manifestations, myositis-specific antibodies or myositis-associated antibodies between the two groups. CONCLUSION: Thromboembolism is a complication of myositis. Lower levels of albumin, diabetes, and coronary heart disease might be risk factors of thromboembolism in myositis patients.

A MYC target long non-coding RNA GATA2-AS1 regulates non-small cell lung cancer growth.

Non-small cell lung cancer (NSCLC) is the most prevalent subtype of lung cancer histologically, and an increasing number of evidences have shown during the past years that long non-coding RNAs (lncRNAs) are involved in tumorigenesis. Here we found a long non-coding RNA, GATA2-AS1, repressing NSCLC cells proliferation via regulating GATA2. GATA2-AS1 gene is located at antisense strand of GATA2 on chromosome while GATA2-AS1 RNA interacts with GATA1 protein at promoter region of GATA2 and then inhibits its transcription. Moreover, GATA2-AS1 is transcriptionally repressed by MYC in NSCLC cells. To conclude, our study discovered the role of lncRNA GATA2-AS1 in human non-small cell lung cancer growth thus providing a potential target for lung cancer drugs.

[Role of circulating T follicular helper subsets and T follicular helper effector memory cells in systemic lupus erythematosus].

Objective: To investigate the role of T follicular helper (Tfh) subsets and T follicular helper effector memory (Tfhem) cells in circulation of patients with systemic lupus erythematosus (SLE), and explore their roles in SLE disease activity index as biomarkers. Methods: This study enrolled 64 patients with SLE and 15 healthy controls. In peripheral blood from patients with SLE and health controls, the percentage of Tfhem (CD3(+)CD4(+)CD45RA(-)CXCR5(+)CCR7(low)PD-1(high)) cells, Tfh (CD3(+)CD4(+)CD127(high)CD25(l)ow CD45RA(-)CXCR5(+)) subset: Tfh1 (CXCR3(+)CCR6(-)Tfh), Tfh2 (CXCR3(-)CCR6(+) Tfh), Tfh17 (CXCR3(-)CCR6(+) Tfh), were detected by flow cytometry. The correlations of Tfhem/Tfh subsets with clinical indicators which we collected were analyzed. Results: The percentage of Tfhem was significantly increased in SLE patients compare to health controls (1.40±1.12 vs 0.51±0.24, P<0.000 1), and it was also correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P=0.015 3) and anti-dsDNA antibody (P=0.003 1), but not with complement C3 (C3), complement C4 (C4), erythrocyte sedimentation rate (ESR), and C reaction protein (CRP). In addition, the percentage of Tfh2, but not Tfh1 or Tfh17, was significantly increased in SLE patients compare to health controls (3.83±2.74 vs 2.18±1.07, P=0.000 4). As compared to anti-dsDNA antibody<25 group, the percentage of Tfh2 in anti-dsDNA antibody>25 group was increased with no significant statistical difference (4.33±3.20 vs 3.70±1.070, P=0.069 6). Conclusion: Our investigation show that Tfhem is associated with SLEDAI and it is a valuable evaluation biomarker for disease process and treatment. Meanwhile Tfhem is also associated with anti-dsDNA antibody, and it plays an important role in autoantibody production in SLE pathogenesis. Tfhem may be a good therapeutic target in SLE. For the meantime, the percentage of Tfh2 is significantly increased in SLE patients, and it had certain correlation with anti-dsDNA antibody, it might be involved in the development of SLE.

[Analysis of 20-year survival rate and prognostic indicators of systemic lupus erythematosus].

Objective: To analyze the 20-year survival rate, causes of death and predictors of systemic lupus erythematosus (SLE). Methods: A retrospective analysis was performed on 217 newly SLE patients who were diagnosed and treated by Peking University People's Hospital before June 2008. The clinical features and serologic data were studied. Survival rate of SLE patients over time, living conditions, causes of death and prognostic indicators of mortality were studied. Results: The 10-, 15-and 20-year cumulative survival rate was 90.3%,88.1%and 79.6%, respectively. Infection and lupus encephalopathy were the main causes of death. Cox regression analysis revealed that lupus nephritis, neuropsychiatric systemic lupus erythematosus and age at the diagnosis were independent risk determinants for mortality. Conclusion: Prognosis of SLE remains to be improved. Early diagnosis, control of SLE organ damage and infection prevention are critical to improve survival of SLE patients.