Chen Jing-Yu, Qiao Kun, Liu Feng, Wu Bo, Xu Xin, Jiao Guo-Qing, Lu Rong-Guo, Li Hui-Xing, Zhao Jin, Huang Jian, et al.
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000839
Abstract
Background:
Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
Methods:
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Results:
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
Conclusions:
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Cai Yue-Ming, Li Ru, Ye Hua, He Jing, Sun Xiao-Lin, Jin Jia-Yang, Liu Jia-Jia, Gan Yu-Zhou, You Xu-Jie, Xu Jing, et al.
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000811
Abstract
Background:
Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort.
Methods:
Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis.
Results:
The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P= 0.013).
Conclusion:
Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.
Wang Pei-Dong, Gao Li, Di Hai-Bo, Li Jing-Qi, Ni Ying-Ying, Wang De-Sheng, Ding Xin-Sheng
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000806
Abstract
Background:
It is a challenge to characterize the consciousness level of patients with severe disturbance of consciousness and predict their prognosis effectively for Chinese doctors. We aimed to investigate the psychometric property and the diagnostic practicality of severe disturbance of consciousness by Chinese Nanjing persistent vegetative state scale (CNPVSS) which was first set up in 1996 and modified in 2001 and 2011.
Methods:
The concurrent validity, inter-rater consistency and diagnostic accuracy of CNPVSS and Chinese version of coma recovery scale-revised (CRS-R) were investigated by assessment of 380 patients with severe disorders of consciousness.
Results:
Total scores of the CNPVSS were correlated significantly with that of the CRS-R, indicating acceptable concurrent validity. Sub-scale analysis showed moderate to high inter-rater reliability and test-retest reliability. CNPVSS was superior to CRS-R on the diagnosis sensitivity. The CNPVSS was able to distinguish 65 patients in emergence from minimal consciousness state who were misclassified as in minimal consciousness state (MCS) by the CRS-R, and it could also distinguish two patients in MCS who were misclassified as in vegetative state by the CRS-R.
Conclusion:
The CNPVSS is an appropriate measurement and is sensitive to distinguish the MCS patients from the VS patients.
Wang Xiao-Jun, Qian Xi-Wen, Zhang Xu, Han Li, Zheng Yu-Qi, Wu Tao, Qin Guo-You, Ye Zhi-Bin, Xiao Jing
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000840
Abstract
Background:
The relationship of uric acid (UA) with the thyroid function among healthy individuals remains unclear. We aimed to examine the relationship between UA contents and thyroid hormone levels in healthy Chinese individuals.
Methods:
This was a cross-sectional study of 1186 Chinese adults (736 men and 450 women) who underwent a health check-up at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) between January 1, 2010 and July 31, 2018. Clinical and thyroid hormone levels were compared in different UA groups (in male and menopause women groups, MG1: UA < 5 mg/dL; MG2: 5 mg/dL ≤ UA< 7 mg/dL; and MG3: UA ≥ 7 mg/dL; in female groups, FG1 to FG3 represent the UA levels of <4 mg/dL, 4 mg/dL ≤ UA< 6 mg/dL, and ≥6 mg/dL, respectively). In addition, natural cubic spline regression, together with Pearson correlation analysis, was performed in investigating the correlation of UA with thyroid hormones.
Results:
After adjusting for confounding factors, low levels of UA (for males, UA < 5.30 mg/dL; for females, UA < 4.05 mg/dL) were negatively correlated with free triiodothyronine (FT3) both in men and women. UA levels between 4.83 and 6.06 mg/dL may act to protect FT3 in women, while UA levels between 6.39 and 7.09 mg/dL may protect FT3 in men. FT3 levels of low-range UA group reduced compared with mid-range UA and the high-range UA groups in both men and women.
Conclusions:
Our results provide epidemiologic evidence to support the negative correlation between low UA contents and FT3 in the Chinese Han population, suggesting that the reduced UA contents may serve as the risk factor to predict poor thyroid function in Chinese individuals.
Duan Hao, Hu Ji-Long, Chen Zheng-He, Li Jue-Hui, He Zhen-Qiang, Wang Zhen-Ning, Zhang Guan-Hua, Guo Xiao-Yu, Liang Lun, Mou Yong-Gao
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000843
Abstract
Background:
Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.
Methods:
CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.
Results:
Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.
Conclusion:
Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.
Chen Mu, Wang Zhi-Quan, Wang Qun-Shan, Sun Jian, Zhang Peng-Pai, Feng Xiang-Fei, Li Wei, Yu Ying, Liu Bo, Mo Bin-Feng, et al.
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000855
Abstract
Background:
Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure.
Methods:
Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively.
Results:
A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak <5 mm) was achieved in all patients. One stroke and four cardiac perforations occurred peri-operatively. At 3-month follow-up, sinus rhythm and satisfactory seal were maintained in 153/178 (86.0%) and 178/178 (100%) patients, respectively. One stroke and one delayed cardiac tamponade occurred, while no device-related thrombus or device migration was observed. During the 1-year follow-up for the earlier enrolled subjects, 52/72 (72.2%) of the patients maintained sinus rhythm. There was no stroke or systemic embolism observed.
Conclusion:
Combining catheter ablation and LAAC in a single procedure can be successfully and safely performed in non-valvular AF patients of Chinese population.
Zhang Xiao-Li, Li Fei, Cui Ye-Qing, Liu Shuang, Sun Hai-Chen
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000838
Abstract
Background:
Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α).
Methods:
TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10-6, 10-7, 10-8 mol/L) for 48 h, and SQ29548 (10-4, 10-6, and 10-7 mol/L), a TxA2r-specific antagonist, for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10-4 mol/L) for 2 h, followed by 10-7 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student’s t test.
Results:
TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2a significantly increased mRNA levels of α-SMA (10-6 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t= 10.70, P < 0.001; 10-7 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t= 10.83, P <0.001; 10-8 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t= 11.40, P < 0.001) and collagen I (10-6 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10-7 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10-8 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10-4 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10-6 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10-7 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t= 15.41, P < 0.001) and α-SMA (10-4 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t= 15.17, P < 0.001; 10-6 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t= 11.29, P < 0.001; 10-7 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t= 12.86, P < 0.001). After being treated with SQ29548 (10-4 mol/L) and then 8-epi-PGF2α (10-7 mol/L), the mRNA levels of a-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t= 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group.
Conclusions:
The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.
Feng Pan-Pan, Fang Xue-Sheng, Zhao Si-Hui, Fu Jun-Yan, Zhang Hui-Ting, Yi Yan-Lin, Li Chang-Yi, Jiang Chun-Ling, Chen Da-Peng
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000773
Abstract
Background:
Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.
Methods:
Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence.
Results:
Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β in Sal B-treated group was significantly lower than that in SASP-treated group.
Conclusions:
These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.
Yao Nian-Ting, Zheng Qian, Xu Zi-Qian, Yin Jian-Hong, Lu Lin-Guang, Zuo Qi, Yang Su, Zhang Chun-Lin, Jiao Ling
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000836
Abstract
Parkinson disease (PD) is the second-most common neurodegenerative disorder. Its main pathological mechanism is the selective degeneration and deletion of dopaminergic neurons in the dense part of the substantia nigra and the damage of dopaminergic neurons caused by the abnormal deposition of a Lewy body, leading to a decreased dopamine level. Positron emission computed tomography (PET)/single photon emission computed tomography (SPECT) is a molecular imaging technology that can directly or indirectly reflect changes in molecular levels by using a specific tracer. With the research and development on the tracers of related enzymes for labeling dopamine transporter and dopamine receptor and for being involved in dopamine formation, this imaging technology has been applied to all aspects of PD research. It not only contributes to clinical work but also provides an important theoretical basis for exploring the pathological mechanism of PD at a molecular level. Therefore, this review discusses the application value of PET/SPECT in PD in terms of early diagnosis, disease severity evaluation, clinical manifestations, differential diagnosis, and pathological mechanism.
Li Tian-Jiao, Wang Rui, Li Qin-Yang, Li Chun-Yu, Jiang Li
Chinese Medical JournalVol.133,No.122020
DOI: 10.1097/CM9.0000000000000764
Abstract
Periodontitis is one of the most prevalent epidemics affecting human health and life recently, and exploration of the pathogenesis and treatment of periodontitis has been valued by scholars. In recent years, sclerostin, a new factor on bone resorption and reconstruction caused by inflammation and mechanical stimulation, has been a research hotspot. This article summarizes the researches on sclerostin in periodontitis development in recent years. Among them, sclerostin has been shown to be a critical negative regulator of bone formation, thereby inhibiting bone remodeling in periodontitis development, and is closely associated with tooth movement. Besides, evidence indicates that the removal of sclerostin seems to reasonably protect the alveolar bone from resorption. Regulation of sclerostin expression is a novel, promising treatment for periodontitis and addresses several complications seen with traditional therapies; accordingly, many drugs with similar mechanisms have emerged. Moreover, the application prospect of sclerostin in periodontal therapy combined with orthodontic treatment is another promising approach. There are also a lot of drugs that regulate sclerostin. Anti-sclerostin antibody (Scl-Ab) is the most direct one that inhibits bone resorption caused by sclerostin. At present, drugs that inhibit the expression of sclerostin have been applied to the treatment of diseases such as multiple myeloma and osteoporosis. Therefore, the application of sclerostin in the oral field is just around the corner, which provides a new therapeutic bone regulation strategy in oral and general health.
Primary central nervous system lymphoma (PCNSL) is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes. This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients. The authors retrieved information from the PubMed database up to September 2019. The annual incidence of PCNSL increased over the last four decades. The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate, which is now the backbone of all first-line treatment polychemotherapy regimens. Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-κB, B cell antigen receptor, and Janus kinases/signal transducer and activator of transcription proteins signal pathways. Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy. In particular, lenalidomide and ibrutinib have demonstrated durable efficiency. Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups, but there is still room to improve outcome by optimizing current chemotherapy and novel agents.