Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).
Methods:
PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.
Results:
Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87-1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71-1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25-1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR= 1.32, 95% CI: 1.14-1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64-1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63-6.07, P = 0.25) between the LTA group and SBRT group.
Conclusions:
Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.
Jingya Zhao, Jinnong Zhang, Yang Jin, Zhouping Tang, Ke Hu, Hui Sun, Mengmeng Shi, Qingyuan Yang, Peiyu Gu, Hongrong Guo, et al.
Chinese Medical JournalVol.135,No.132022
DOI: 10.1097/CM9.0000000000002104
Abstract
Background:
To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.
Methods:
This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.
Results:
A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression.
Conclusions:
SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.
Trial registration:
Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1
Lina Zhang, Di Wu, Mingyue Xu, Yonghui Bian, Youcun Wang, Guangkai Gao, Qing Sun
Chinese Medical JournalVol.135,No.132022
DOI: 10.1097/CM9.0000000000001942
Abstract
Background:
Carbon monoxide (CO) poisoning remains a major cause of accidental injuries and multiple studies have indicated that CO is also associated with significantly severe or long-term toxicity to the central nervous system. Given that CO poisoning causes serious morbidity and mortality, a better understanding of epidemiological features and clinical characteristics of acute CO poisoning in China is crucial.
Methods:
We collected the clinical data of acute CO poisoning in patients between November 2019 and April 2020 across Shandong province, China and analyzed its characteristics focusing on the weekly amount and the severity of the confirmed cases.
Results:
A total number of 21,088 acute CO poisoning cases were diagnosed. The overall incidence of acute CO poisoning was approximately 0.021%. On severity rankings, 63% of confirmed cases (n = 13,378) were mild, 27% (n = 5635) were moderate, and 10% (n = 2075) were severe. Interestingly, the coastal cities had more confirmed cases than the inland/suburban areas in Shandong. Meanwhile, the number of confirmed cases was negatively correlated with the local mean daily temperature (P = 0.0167).
Conclusions:
Mild acute CO poisoning cases accounted for the majority of all confirmed cases during the winter of 2019. In Shandong province, which is located in east China, residents of the coastal cities are more susceptible to CO poisoning than residents of inland cities.
Wei Xiao, Longyi Du, Linli Cai, Tiwei Miao, Bing Mao, Fuqiang Wen, Peter Gerard Gibson, Deying Gong, Yan Zeng, Mei Kang, et al.
Chinese Medical JournalVol.135,No.132022
DOI: 10.1097/CM9.0000000000002050
Abstract
Background:
Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays.
Methods:
Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed.
Results:
The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) (χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) (χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) (χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) (χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) (P = 0.734). Sputum LFD had similar specificity (91% [81/89]) (χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) (χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) (χ2 = 6.95, P = 0.008), BDG (χ2 = 10.43, P = 0.001), and fungal culture (χ2 = 12.70, P < 0.001).
Conclusions:
Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.
Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy.
Methods:
Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020.
Results:
A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight (t = 4.694, P < 0.001), BMI categories (χ2 = 19.215, P = 0.001), and incidence of metabolic disorders (χ2 = 24.841, P < 0.001); the BMI categories and weight change had no effect on the OS. Both univariate (χ2 = 6.771, P = 0.009) and multivariate survival analyses (hazard ratio = 2.775, 95% confidence interval [CI]: 1.326-5.807, P = 0.007) showed that low high-density lipoprotein cholesterol (HDL-C) levels at diagnosis had a negative impact on the OS. The multivariate logistic regression analysis showed that the HDL-C level at diagnosis (odds ratio [OR] = 2.200, 95% CI: 0.996-4.859, P = 0.051) and metabolic disorders after chemotherapy (OR= 1.514, 95% CI: 1.047-2.189, P = 0.028) are risk factors for poor prognosis in patients with breast cancer.
Conclusions:
Chemotherapy led to weight gain and aggravated the metabolic disorders in patients with breast cancer. Low HDL-C levels at diagnosis and metabolic disorders after chemotherapy may have negative effects on the OS and prognosis of patients with breast cancer.
So far, there is a paucity of real-world data on the syphilis serological responses to the first-line treatment during pregnancy, and there is no relevant study on the necessity of anti-syphilis treatment during pregnancy for those patients who have been treated for syphilis before pregnancy for the prevention of mother-to-child transmission, which might provide valuable insight into treatment effectiveness and optimal management of pregnant women with syphilis.
Methods:
A retrospective study on 10 years of real-world data was performed for accumulative 410 Chinese pregnant women with syphilis. The descriptive statistics were conducted in the study, and toluidine red unheated serum test (TRUST) titer responses to penicillin treatment in syphilis-infected pregnant women, and the associations with congenital syphilis were investigated. We divided the patients into two groups according to the history of anti-syphilis treatment before pregnancy (patients diagnosed with syphilis who had received anti-syphilis treatment before pregnancy, and patients screened and diagnosed with syphilis during pregnancy who had no previous history of anti-syphilis treatment).
Results:
The rate of congenital syphilis in this study was 6.2% (25/406). There was no significant difference in the rate of congenital syphilis between patients who received anti-syphilis treatment before pregnancy and those who did not. Secondary syphilis and high baseline serum TRUST titer (≥1:8) in pregnant women were independent risk factors for congenital syphilis.
Conclusions:
For the prevention of congenital syphilis, anti-syphilis treatment during pregnancy for syphilis seropositive pregnant women is needed, regardless of whether the patient has received anti-syphilis treatment before pregnancy, especially for those patients with secondary syphilis or high baseline serum TRUST titer, thus, timely surveillance, early diagnosis to timely treatment, and close syphilis reexamination during posttreatment follow-up, may help to reduce the above-mentioned risk factors for congenital syphilis.
Na Ma, Yan Li, Siyu Wang, Mengpu Li, Yongjun Li, Hu Ai, Hui Zhu, Yang Wang, Fajin Guo, Junhong Ren
Chinese Medical JournalVol.135,No.132022
DOI: 10.1097/CM9.0000000000002162
Abstract
Background:
This study aims to observe the dynamic changes of renal artery (RA) disease and cortical blood perfusion (CBP) evaluated by contrast-enhanced ultrasound (CEUS) after percutaneous transluminal renal artery stenting (PTRAS) in patients with severe atherosclerotic renal artery stenosis (ARAS) and to analyze the relationship between CBP and prognosis.
Methods:
This was a single-center retrospective cohort study. A total of 98 patients with unilateral severe ARAS after successful PTRAS in Beijing Hospital from September 2017 to September 2020 were included. According to renal glomerular filtration rate (GFR) detected by radionuclide imaging at 12 months after PTRAS, all patients were divided into the poor prognosis group (n = 21, GFR decreased by ≥20% compared with baseline) and the control group (n = 77, GFR decreased by < 20% or improved compared with baseline). Renal artery stenosis was diagnosed by digital subtraction angiography, and renal CBP was evaluated by CEUS using TomTec Imaging Systems (Germany) before PTRAS, at 6 months and 12 months after discharge. The receiver operating characteristic (ROC) curve with area under the curve (AUC) was used to analyze the predictive value of CBP parameters, including area under ascending curve (AUC1), area under the descending curve (AUC2), rising time (RT), time to peak intensity (TTP), maximum intensity (IMAX), and mean transit time (MTT) for poor prognosis.
Results:
Among the 98 patients, there were 52 males (53.1%), aged 55-74 years old, with an average age of 62.1 ± 8.7 years, and an average artery stenosis of 82.3 ± 12.9%. The poor prognosis group was associated with significantly increased incidence of diabetes (76.2% vs. 41.6%), and lower levels of GFR of the stenotic kidney (21.8 mL/min vs. 25.0 mL/min) and total GFR (57.6 mL/min vs. 63.7 mL/min) (all P < 0.05), compared with the control group (P < 0.05). In addition, the rate of RA restenosis was significantly higher in the poor prognosis group than in the control group (9.5% vs. 0, χ2 = 9.462, P = 0.002). Compared with the control group, the poor prognosis group was associated with significantly decreased baseline AUC1 and AUC2, and extended duration of TTP and MTT (P < 0.05). At 6 months and 12 months of follow-up, patients in the control group were associated with markedly increased AUC1, AUC2, and IMAX, and shorter duration of RT and MTT (P < 0.05). The ROC curve showed that the predictive values of AUC1, AUC2, RT, TTP, IMAX, and MTT for poor prognosis were 0.812 (95% CI: 0.698-0.945), 0.752 (95% CI: 0.591-0.957), 0.724 (95% CI: 0.569-0.961), 0.720 (95% CI: 0.522-0.993), 0.693 (95% CI: 0.507-0.947), and 0.786 (95% CI: 0.631-0.979), respectively.
Conclusions:
Preoperative renal CBP in severe ARAS patients with poor prognosis is significantly reduced, and does not show significant improvement after stent treatment over the first year of follow-up. The parameter AUC1 may be a good predictor for renal dysfunction after PTRAS in severe ARAS patients.
Circular RNAs (circRNAs) are endogenous non-coding RNAs, some of which have pathological roles. The current study aimed to explore the role of circRNA BTG3-associated nuclear protein (circ-BANP) binding with let-7f-5p and its regulation of the toll-like receptor 4 (TLR4)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA).
Methods:
Circ-BANP, let-7f-5p, and TLR4 expressions in HCC samples were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Bioinformatics prediction, RNA pull-down assay, and dual luciferase reporter gene assay were used to analyze the relationships among circ-BANP, let-7f-5p, and TLR4. Huh7 cells were used to generate an in vitro model of residual HCC, defined as Huh7-H cells, which were transfected with either a plasmid or the sequence of circ-BANP, let-7f-5p, or TLR4. Expression of circ-BANP, let-7f-5p, and TLR4 mRNA was determined by RT-qPCR. TLR4, STAT3, p-STAT3, vascular endothelial growth factor A, vascular endothelial growth factor receptor-2, and epithelial-mesenchymal transformation (EMT)-related factors proteins were determined by Western blotting. Cell proliferation was determined by cell counting kit-8 and 5-Ethynyl-2’-deoxyuridine (EdU) assay and cell migration and invasion by Transwell assay. Animal studies were performed by inducing xenograft tumors in nude mice.
Results:
Circ-BANP and TLR4 mRNAs were upregulated in HCC tissues (the fold change for circ-BANP was 1.958 and that for TLR4 was 1.736 relative to para-tumors) and expression further increased following insufficient RFA (fold change for circ-BANP was 2.407 and that of TLR4 was 2.224 relative to para-tumors). Expression of let-7f-5p showed an opposite tendency (fold change for let-7f-5p in HCC tissues was 0.491 and that in tumors after insufficient RFA was 0.300 relative to para-tumors). Competitive binding of circ-BANP to let-7f-5p was demonstrated and TLR4 was identified as a target of let-7f-5p (P < 0.01). Knockdown of circ-BANP or elevation of let-7f-5p expression inhibited the TLR4/STAT3 signaling pathway, proliferation, invasion, migration, angiogenesis, and EMT in Huh7 and Huh7-H cells (P < 0.01). The effects induced by circ-BANP knockdown were reversed by let-7f-5p inhibition. Overexpression of TLR4 reversed the impact of let-7f-5p upregulation on the cells (P < 0.01). Silencing of circ-BANP inhibited the in vivo growth of residual HCC cells after insufficient RFA (P < 0.01).
Conclusions:
Knockdown of circ-BANP upregulated let-7f-5p to inhibit proliferation, migration, and EMT formation in residual HCC remaining after insufficient RFA. Effects occur via regulation of the TLR4/STAT3 signaling pathway.
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear.
Methods:
Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells. Blue-native polyacrylamide gel electrophoresis (PAGE) and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system (MICOS). Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10. Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were used to examine the influence of CHCHD2 in vivo.
Results:
We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model. Furthermore, we identified that CHCHD2 interacted with Mic10, and overexpression of CHCHD2 can protect against MPP+-induced MICOS impairment, while knockdown of CHCHD2 impaired the stability of MICOS.
Conclusion:
This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex, which contributes to protecting mitochondrial function in PD.
The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.
Methods:
Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.
Conclusion:
The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.
Trial registration:
Chinese Clinical Trial Registry, ChiCTR1800017277.
