Xiaoqi Wang, Ruihao Huang, Xiaohui Zhang, Xi Zhang
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002235
Abstract
Hematopoietic stem cell transplantation (HSCT) is a highly effective and unique medical procedure for the treatment of most hematological malignancies. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then, the field has evolved and expanded worldwide. The first successful allogenic HSCT (allo-HSCT) in China was conducted in 1981. Although the development of allo-HSCT in China lagged, China has since made considerable contributions to the process of HSCT worldwide, with more than 10,000 HSCTs performed annually. In particular, haploid HSCT (haplo-HSCT) technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in China. Currently, the number of haplo-HSCT procedures exceeds 5000 per year, and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications, relapse, and infection management. In addition, innovative haplo-HSCT technologies developed by different medical transplantation centers, such as Soochow, Zhejiang, Fujian, Chongqing, and Anhui, have emerged, providing inspiration for the refinement of global practice. This review will focus on the current activity in this field and highlight important trends that are vital in China’s allo-HSCT process, examining the current viewpoint and future directions.
Response to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients.
Methods:
The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People’s Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated.
Results:
Forty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs. 15.5 months, P = 0.0005) and OS (11.1 months vs. not reached, P = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs. 15.5 months, P = 0.0532) rather than OS (P = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs. 4.3 months, P = 0.1894). More metastatic organs involved were associated with inferior PFS (P = 0.0052) but not OS (P = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[φ]: 0.516, P = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4).
Conclusions:
Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.
Lei Tang, Lina Yang, Wenwen Chen, Chunyang Li, Yu Zeng, Huazhen Yang, Yao Hu, Yuanyuan Qu, Huan Song, Xiaoxi Zeng, et al.
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002234
Abstract
Background:
The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee–CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.
Methods:
A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data (n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results.
Results:
Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed (P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee–CKD association.
Conclusions:
In addition to the overall inverse coffee–CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.
Yanhua Huang, Zuoteng Wang, Bing Zhao, Yahui Ma, Yanan Ou, Hao Hu, Xiaohe Hou, Jintai Yu, Lan Tan
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002228
Abstract
Background:
Previous studies have shown that inflammation plays an important role in intracranial atherosclerotic stenosis (ICAS). The platelet-to-lymphocyte ratio (PLR) has recently emerged as a potential inflammatory biomarker. This study aimed to explore the association of the PLR with ICAS in a Chinese Han population.
Methods:
A total of 2134 participants (518 with ICAS, 1616 without ICAS) were enrolled in this study. ICAS was defined as atherosclerotic stenosis >50% or the occlusion of several main intracranial arteries. Multivariable logistic regression analyses were used to assess the association of the PLR with ICAS. Additional subgroup analyses were performed according to age (<60 vs. ≥ 60 years) and acute ischemic stroke.
Results:
Multivariate regression analysis showed that a high PLR was associated with a higher risk of ICAS in all participants (P < 0.001). Compared with the lowest quartile, the fourth PLR quartile was significantly associated with ICAS (OR 1.705, 95% confidence interval 1.278–2.275, P < 0.001). In the subgroups stratified by age, an association between the PLR and ICAS was found in the late-life group (P < 0.001), but not in the mid-life group (P = 0.650). In the subgroups stratified by acute ischemic stroke, the relationship between an elevated PLR and a higher risk of ICAS remained unchanged (stroke group, P < 0.001; non-stroke group, P = 0.027).
Conclusions:
An elevated PLR was associated with a higher risk of ICAS in a Chinese Han population. The PLR might serve as a potential biomarker for ICAS in the elderly population.
Rushikesh Shah, Huimin Chen, Lucie F. Calderon, Tonia Gooden, Maryam Mubashir, Shazia Rashid, Syed Musa Raza, Allison Derise, Grace Mccurdy, Brenna Sanders, et al.
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002068
Abstract
Background:
Gastroparesis is a debilitating medical condition with limited treatment options. Gastric per-oral pyloromyotomy (G-POEM) has emerged as a promising treatment option with remarkable short-term clinical success shown in multiple studies. While the post-procedure protocol is not standardized across many centers, the majority of the centers observes these patients in the hospital after the procedure for monitoring. In this single-center prospective study, we evaluated the safety and feasibility of same day discharge after the G-POEM procedure.
Methods:
All the patients with refractory gastroparesis undergoing G-POEM from October 2019 to March 2020 were enrolled. A total of 25 patients were enrolled in the procedure. Based on the pre-defined criteria, patients were either discharged on the same day after the procedure or admitted to the hospital for further observation. The patient and procedure-related data were extracted from the chart review. Univariate analysis was performed (chi-squared test) on categorical variables after organizing categorical variables as numeric counts or percentages. The student t test was performed on continuous variables after reporting as mean and standard deviation. For analysis with a smaller sample size, Fisher exact and Mann–Whitney tests were used.
Results:
A total of 25 patients were enrolled. The technical success of G-POEM was 100% and clinical success was 80% (20/25) at 1-month follow-up. Of the 25 patients, 9 patients (36%) were discharged on the same day according to the procedure from the recovery unit. Of the remaining 16 patients who were admitted to the hospital post-procedure, 10 (40%) were admitted due to procedure-related causes while other admissions were either pre-planned or due to social reasons. The average Charlson comorbidity index was lower in the same day discharge group (P < 0.05). The number of patients requiring double myotomy was higher in the same day discharge group (P < 0.05). The overall complication rate of G-POEM in the study cohort was 12% (3/25) with all complications being mild without any severe adverse events.
Conclusion:
G-POEM is a safe and effective method of treatment for refractory GP with higher clinical success in short-term follow-up. The same day discharge after G-POEM is safe and feasible in >50% of patients with close periprocedural monitoring.
Zheng Zhao, Lin Cai, Si Zhang, Heng Zhang, Xiaoyang Liu, Chenglong Li, Yan Zhao, Jianzhong Zhang
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002130
Abstract
Background:
Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, there are limited reports on the relationship between serum uric acid levels and biological treatment efficacy. The purposes of this study were to compare the differences in serum uric acid levels between patients with psoriasis and healthy controls and analyze the risk of hyperuricemia.
Methods:
A total of 196 patients with psoriasis and 191 age- and sex-matched healthy controls were enrolled in this retrospective cohort study. One hundred and twenty-seven patients with severe psoriasis were treated with biologics. Sixty-eight patients received adalimumab, and 59 patients received secukinumab. Serum uric acid levels were measured at baseline, week 24, and week 48 of treatment.
Results:
Patients with psoriasis had higher serum uric acid levels than healthy controls (6.4 ± 1.7 mg/dL vs. 5.7 ± 1.5 mg/dL, P < 0.001). Hyperuricemia was found in 33.7% (66/196) of patients with psoriasis, which was significantly higher than that in healthy controls (13.1% [25/191], P < 0.001). Serum uric acid levels and hyperuricemia were not related to the severity of psoriasis (P > 0.05). No significant changes in serum uric acid levels and hyperuricemia were observed following adalimumab treatment (P > 0.05). The serum uric acid level in patients treated with secukinumab was 6.7 ± 1.6 mg/dL at week 24, which was not statistically different from that at baseline (6.6 ± 1.4 mg/dL, P = 0.885). Serum uric acid levels were significantly decreased at week 48 (6.3 ± 1.5 mg/dL vs. 6.6 ± 1.4 mg/dL, P = 0.007) in patients treated with secukinumab. Secukinumab had no significant effect on hyperuricemia either (P > 0.05).
Conclusions:
The serum uric acid levels and prevalence of hyperuricemia in patients with psoriasis were significantly higher than those in healthy controls. Secukinumab treatment for 48 weeks successfully decreased serum uric acid levels in patients with psoriasis, whereas adalimumab had no significant effect on serum uric acid levels.
Wenmin Fei, Yang Han, Ang Li, Keke Li, Xiaoli Ning, Chengxu Li, Wenju Wang, Rusong Meng, Yong Cui
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002151
Abstract
Background:
The dermoscopic features of rosacea have already been reported. However, the current findings are incomplete, and little is known about phymatous rosacea. Hence, this study aimed to summarize and compare the dermoscopic features and patterns of three rosacea subtypes (erythematotelangiectatic [ETR], papulopustular [PPR], and phymatous [PHR]) in the Chinese Han population and to evaluate whether these features differ with patients’ genders, ages, and durations.
Methods:
Dermoscopic images of 87 rosacea patients were collected in non-polarized and polarized dermoscopy contact modes at 20-fold magnification. Dermoscopic features, including vessels, scales, follicular findings, and other structures, were summarized and evaluated.
Results:
The reticular linear vessels and red diffuse structureless areas of ETR were distinctive. For PPR, red diffuse structureless areas, reticular linear vessels, yellow scales, follicular plugs, and follicular pustules were typical dermoscopic criteria. The common dermoscopic features of PHR were: orange diffuse structureless areas, linear vessels with branches, perifollicular white color, orange focal structureless areas, and white lines. The following features statistically differed among the three rosacea subtypes: reticular linear vessels (P < 0.001), unspecific linear vessels (P= 0.005), linear vessels with branches (P < 0.001), yellow scales (P = 0.001), follicular plugs (P < 0.001), perifollicular white color (P < 0.001), red diffuse structureless areas (P = 0.022), orange diffuse structureless areas (P < 0.001), red focal structureless areas (P = 0.002), orange focal structureless areas (P = 0.003), white lines (P < 0.001), follicular pustules (P < 0.001), and black vellus hairs (P < 0.001).
Conclusions:
The dermoscopic patterns of ETR are red diffuse structureless areas and reticular linear vessels. For PPR, the pattern comprehends combinations of red diffuse structureless areas, reticular linear vessels, yellow scales, follicular plugs, and follicular pustules. Meanwhile, PHR is characterized by remarkable orange diffuse structureless areas, linear vessels with branches, perifollicular white color, orange focal structureless areas, and white lines.
The CHA2DS2–VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA2DS2–VASc score in stroke and all-cause mortality.
Methods:
Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA2DS2–VASc score model.
Results:
Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364–7.813, P = 0.008). Adding the H19 expression level to the CHA2DS2–VASc score significantly improved the discrimination and reclassification power of the CHA2DS2–VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889–5.760, P = 0.087), although it appeared to have no significant improvement for the CHA2DS2–VASc model for predicting all-cause mortality.
Conclusions:
Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA2DS2–VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.
Yong Wu, Hanyuan Yang, Xiangbin Guo, Hui Du, Xiaofeng Gong
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002192
Abstract
Background:
Total ankle replacement (TAR) is a viable option for the treatment of end-stage ankle arthritis. In China, the INBONE-II implant is the only total ankle prosthesis approved since 2016. The purpose of this study is to report a large sample of findings for the TAR with INBONE-II prosthesis.
Methods:
A total of 64 patients with end-stage ankle arthritis, who underwent primary TAR using INBONE-II by the same surgeon from 2016 to 2019, at a single institution were included in this retrospective, single-center study. Clinical data, radiographic findings, survival rate, and complications were recorded and assessed pre-operatively and at the most recent follow-up.
Results:
A total of 64 patients were available for follow-up at least 2 years after surgery; the mean follow-up duration for clinical outcomes was 37.9 months (24–59 months), and for radiographic findings was 22.8 months (12–59 months). There were significant improvements (P < 0.01) in the American Orthopedic Foot and Ankle Society hindfoot scale, the visual analog scale for pain, and the Short Form-36. There were statistically significant differences between pre-operative and post-operative comparisons of the talar tilt angle (TT) and the tibial lateral surface angle (TLS) in the radiographic findings (TT from 4.7 ± 4.3° to 1.3 ± 1.3°, TLS from 80.4 ± 7.7° to 87.4 ± 2.3°, P < 0.01). There was no statistically significant difference in improvement of the tibial anterior surface angle (P = 0.14). Ten complications (all low grade) were recorded according to the Glazebrook classification system. The survivorship of the prosthesis was 100% (64/64).
Conclusion:
Patients who underwent TAR with INBONE-II prosthesis demonstrated significant improvements in all measures of pain and function as well as in radiographic findings. High survival and a low incidence of complications were observed in this study.
Zhengyi Cai, Xinmiao Jia, Mingsheng Liu, Xunzhe Yang, Liying Cui
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002090
Abstract
Background:
Epigenetics, and especially DNA methylation, contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). This study aimed to investigate the role of DNA methylation in SALS using whole blood of SALS patients.
Methods:
In total, 32 SALS patients and 32 healthy controls were enrolled in this study. DNA was isolated from whole blood collected from the participants. DNA methylation profiles were generated using Infinium MethylationEPIC BeadChip.
Results:
We identified 34 significant differentially methylated positions (DMPs) in whole blood from SALS patients, compared with the healthy controls. Of these DMPs, five were hypermethylated and 29 were hypomethylated; they corresponded to 13 genes. For the DMPs, ATAD3B and BLK were hypermethylated, whereas DDO, IQCE, ABCB1, DNAH9, FIGN, NRP1, TMEM87B, CCSAP, ST6GALNAC5, MYOM2, and RUSC1-AS1 were hypomethylated. We also identified 12 differentially methylated regions (DMRs), related to 12 genes (NWD1, LDHD, CIS, IQCE, TNF, PDE1C, LGALS1, CSNK1E, LRRC23, ENO2, ELOVL2, and ELOVL2-AS1). According to data from the Kyoto Encyclopedia of Genes and Genomes database, DNAH9 and TNF are involved in the amyotrophic lateral sclerosis (ALS) pathway. Correlation analysis between clinical features and DNA methylation profiling indicated that the methylation level of ELOVL2 and ARID1B was positively associated with the age of onset (r = 0.86, adjust P = 0.001) and disease duration (r = 0.83, adjust P = 0.01), respectively.
Conclusions:
We found aberrant methylation in DMP- and DMR-related genes, implying that many epigenetic alterations, such as the hypomethylation of DNAH9 and TNF, play important roles in ALS etiology. These findings can be helpful for developing new therapeutic interventions.
Ruixi Zhou, Junjie Ying, Xia Qiu, Luting Yu, Yan Yue, Qian Liu, Jing Shi, Xihong Li, Yi Qu, Dezhi Mu
Chinese Medical JournalVol.135,No.122022
DOI: 10.1097/CM9.0000000000002010
Abstract
Background:
Sepsis, a serious condition with high mortality, usually causes sepsis associated encephalopathy (SAE) that involves neuronal cell death. However, the cell death programs involved and their underlying mechanisms are not clear. This study aimed to explore the regulatory mechanisms of different cell death programs in SAE.
Methods:
A neonatal rat model of SAE was established by cecal ligation and perforation. Survival rate and vital signs (mean arterial pressure and heart rate) were monitored, nerve reflexes were evaluated, and cortical pathological changes were observed by hematoxylin and eosin staining. The expression of pyroptosis, apoptosis, and necroptosis (PANoptosis)-related proteins, mitogen-activated protein kinase (MAPK), and its upstream regulator toll-like receptor 9 (TLR9) were detected. The expression of TLR9 in neurons was observed by immunofluorescence staining. The ultrastructure of neurons was observed by transmission electron microscope.
Results:
First, PANoptosis was found in cortical nerve cells of the SAE rats. Meanwhile, the subunits of MAPKs, p38 MAPK, Jun N-terminal kinase, and extracellular signal-regulated kinase (ERK) were activated. After pharmacologically inhibiting each of the subunits, only p38 MAPK was found to be associated with PANoptosis. Furthermore, blocking the p38 MAPK signaling pathway activated necroptosis but inhibited apoptosis and pyroptosis. When necroptosis was pharmacologically inhibited, apoptosis and pyroptosis were reactivated. Finally, we found that the expression of TLR9, a regulator of MAPKs, was significantly increased in this model. After down-regulation of TLR9, p38 MAPK, and ERK signaling pathways were inhibited, which led to the inhibition of PANoptosis. Further analysis found that down-regulation of TLR9 improved the survival rate and reduced the pathological changes in SAE rats.
Conclusions:
Our study showed that the programs comprising PANoptosis are activated simultaneously in SAE rats. TLR9 activated PANoptosis through the p38 MAPK signaling pathway. TLR9 may work as a potential target for SAE treatment.
