OBJECTIVE: Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population. METHODS: A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke. RESULTS: All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups. CONCLUSION In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.
Humans ; Cholesterol, LDL ; Retrospective Studies ; Percutaneous Coronary Intervention/adverse effects* ; Coronary Artery Disease/surgery* ; Cholesterol ; Cholesterol, HDL ; Stroke/etiology* ; Treatment Outcome ; Risk Factors

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

Objective:To analyze the expression of targeting protein for Xklp2 (TPX2) in kidney renal clear cell carcinoma (KIRC) and its clinical significance.Methods:The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology, the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database, which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage, molecular subtypes, lymph node metastasis, and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins, and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database.Results:Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% (26/54) in cancer tissues, which was higher than that in paracancerous tissues (20.37%, 11/54) ( χ2=9.25, P=0.002). The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 (1.49, 2.42), normal tissue: 0.35 (0.24, 0.57), U=2 297.00, P<0.001]. The expression of TPX2 mRNA was related to the clinical stage ( χ2=34.36, P<0.001), molecular subtypes ( χ2=30.15, P<0.001), and lymph node metastasis status ( χ2=27.21, P<0.001) of KIRC patients. The 5-year survival rate (53.80%) in patients with high TPX2 expression was lower than that in patients with low TPX2 expression (74.40%, χ2=18.87, P<0.001). STRING database protein interaction network construction obtained 20 TPX2-related proteins, and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells ( r=0.30, P<0.001), CD8 + T cells ( r=0.23, P<0.001), CD4 + T cells ( r=0.18, P<0.001), macrophages ( r=0.20, P<0.001), neutrophils ( r=0.31, P<0.001), dendritic cells ( r=0.39, P<0.001) infiltration and most of its biomarkers (all P<0.05). It was positively correlated with immune checkpoint PD-1 ( r=0.31, P<0.001) and CTLA-4 ( r=0.27, P<0.001), but not correlated with PD-L1 ( r=0.07, P=0.146) . Conclusion:TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.

Abstract: Objective To detect the polymorphisms of drug resistance-related genes pvcrt-o and pvmdr1 of Plasmodium vivax in lazan city in the China-Myanmar border, in order to guide the treatment plan of Plasmodium vivax. Methods A total of 48 Plasmodium vivax samples were collected from Lazan in the China-Myanmar border in 2007, and fragments of pvcrt-o and pvmdr1 genes were amplified by PCR and sequenced. The sequences were aligned with the Salvador I (Sal-I) strain reference genome sequences to determine the presence of SNPs. Results The target fragments of pvcrt-o gene were amplified from 39 Plasmodium vivax samples, while pvmdr1 genes were amplified from 40 samples. Amongst them, 25 samples had AAG insertion before the 10th amino acid (K10 insertion) of pvcrt-o gene, accounting for 64.1%. Non-synonymous mutations were detected at three loci of pvmdr1 gene (T958M, Y976F, and F1076L), the mutation rates were 100%, 22.5%, and 55.0%, respectively. There were three haplotypes of pvmdr1 gene, of which the triple mutant 958M/976F/1076L accounted for 22.5% (9/40), the double mutant 958M/Y976/1076L accounted for 32.5% (13/40), and the single mutant 958M/Y976/F1076 accounted for 45.0% (18/40). The proportion of strains with pvcrt-o and pvmdr1 gene mutation is 63.16%, which is significantly different from those only with pvmdr1 mutation. Conclusions The proportion of pvcrt-o and pvmdr1 gene mutation of 48 Plasmodium vivax isolates is high in the China-Myanmar border, and there is a certain degree of correlation between the two gene mutations. To assess changes in Plasmodium vivax drug resistance in this region, it is required to improve the surveillance of these two molecular markers.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

AIM: To observe the macular retina vascular density of patients with acute central retinal artery occlusion(CRAO)by optical coherence tomography angiography(OCTA)and to analyze the relationship with retinal circulation time of these patients on fundus fluorescein angiography(FFA).METHODS: Retrospective case analysis. A total of 43 patients(43 eyes)from January 2019 to March 2021 admitted to Shaanxi Eye Hospital with clinical diagnosis of acute CRAO(course of disease ≤7d)were included. All patients underwent FFA, OCTA, best corrected visual acuity(BCVA)examination and thrombolytic therapy. The patients with enhanced or unchanged retinal blood flow signal in the affected eye showed on OCTA before treatment compared with the contralateral healthy eye were assigned to group A, and the patients with retinal blood flow signal of the affected eye was lower than that in the contralateral healthy eye by OCTA were assigned to group B. Image J software was used for OCTA image processing to evaluate the macular retina vascular density before treatment, and FFA examination was performed to record the affected retinal circulation time before treatment.RESULTS: The retinal vascular density of patients in the affected eye and the contralateral healthy eye in group A was higher than that in group B(25.08%±4.40% vs 12.24%±3.41%, 25.72%±2.70% vs 17.89%±4.55%, all P<0.001), the filling time(FT)of retinal artery trunk to terminal in group B [96(20.50, 193.50)s] was longer than that in group A [11(5.00, 19.50)s](P<0.001). The course of disease, the retinal vascular density of contralateral healthy eye and FT were related factors of retinal vascular density of the affected eye(all P<0.05), and the influence strength order was FT, course of disease and the retinal vascular density of contralateral healthy eye, in which the course of disease and FT was negatively correlated with the retinal vascular density.CONCLUSION: OCTA retinal vascular density was correlated with FFA retinal circulation time in CRAO patients.

Through consulting the ancient herbal and medical books， combined with the field investigation， the name， origin， collection and processing of Dendrobium medicinal materials were researched， which provided a basis for the development of famous classical formulas containing this kind of herbs. Due to the wide distribution of D. officinale， the Dendrobium species represented by D. officinale and D. huoshanense， which are short， fleshy and rich in mucus， should be the most mainstream of Dendrobium medicinal materials in previous dynasties. Compared with Shihu， Muhu with loose texture， long and hollow is born on trees. According to the characteristic description， it should be D. nobile， D. fimbriatum and so on， of which D. nobile was the mainstream. The Chinese meaning of Jinchai was confused in the past dynasties， so it was not suitable to be treated as a plant name. The production areas of Dendrobium medicinal materials in the past dynasties have changed with the discovery of varieties， artificial cultivation and other factors. Lu'an， Anhui province， was the earliest recorded in the Han and Wei dynasties. Since the Tang and Song dynasties， it had been extended to Guangdong and Guangxi， and it was considered that "Dendrobii Caulis in Guangnan was the best". In the Ming dynasty， Sichuan and Zhejiang products were highly praised， and in the Qing dynasty， Huoshan products were highly praised. Dendrobium medicinal materials had been used as medicine by stems in all dynasties. The medicinal materials were divided into fresh products and dry products. The fresh products can be used immediately after removing the sediment from the roots. The dry products need further processing， most of them used wine as auxiliary materials for steaming， simmer to paste or decoction into medicine. D. officinale and D. huoshanense have special processing specifications since the middle of Qing dynasty， that is， "Fengdou". According to the research results， in Ganluyin， the effect of Dendrobium medicinal materials is mainly heat clearing， and D. nobile with bitter taste can be selected. The main effect of Dendrobium medicinal materials in Dihuang Yinzi is tonic， D. officinale or D. huoshanense can be selected.

Objective: To investigate the effect of centrosomal protein Cep63 on the apoptosis of papillary thyroid carcinoma (PTC) cell lines TPC-1 and underlying mechanism. Methods: With collected PTC tissues and adjacent tissues, Cep63 expression was detected by RT-qPCR and its relationship with clinicopathological factors was analyzed. The experiment included negative control group (NC), low expression group (Cep63(-)) and overexpression group (Cep63(+)), and wild-type TPC-1 cells were transfected with Cep63 lentivirus. The efficiency of Cep63 was detected by western blot (WB) and qRT-PCR. Cell proliferation ability was detected by plate cloning experiment and MTT assay. Cell apoptotic rate was detected by flow cytometry, and expression levels of apoptosis-related proteins were detected by immunohistochemistry and WB. The t-test was used to compare the differences in the means between the two groups, the one-way analysis of variance was used to compare multiple groups, and the chi-square test was used to analyze the association between gene expression levels and pathological factors. Results: Compared with NC group, cell proliferation ability was significantly decreased in Cep63(-) group (3.18±0.07 vs. 2.14±0.09, t=8.54, P<0.01) and significantly increased in Cep63(+) group (3.18±0.07 vs. 3.58±0.10, t=3.21, P<0.05). Apoptotic rates in NC, Cep63 (-) and Cep63 (+) groups were respectively 3.03%±0.24%, 8.66%±0.44% and 1.17%±0.44%, and the flow cytometry showed that the low expression of Cep63 significantly increased the apoptosis TPC-1 cells (F=157.7, P<0.001). Bcl-2 protein expression levels of NC, Cep63 (-) and Cep63 (+) groups were respectively 1.07±0.03, 0.49±0.01 and 1.99±0.09, and BAX protein expression levels of three groups were respectively 0.64±0.02, 1.06±0.01 and 0.21±0.03. WB showed that the expression level of Bcl-2 decreased (F=183.2, P<0.001), while the expression level of BAX was significantly up-regulated (F=283.7, P<0.001). Conclusion: Cep63 may regulate the apoptotic process of TPC-1 cells through Bcl-2/BAX pathway and Cep63 may be a potential oncogene of PTC.
Apoptosis ; Carcinoma, Papillary/genetics* ; Cell Cycle Proteins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome