Background To compare the safety and efficacy of the traditional Chinese medicine Shenqi particle and standard therapy with prednisone and cyclophosphamide (control) in adult patients with idiopathic ...membranous nephropathy (IMN). Study Design Open-label, multicenter, parallel, randomized, controlled clinical trial. Setting & Participants From April 2008 to February 2011, a total of 190 patients with biopsy-proven IMN from 7 hospitals in China participated in the study. All patients had nephrotic syndrome with estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2. Intervention Shenqi particle (9.6 g 3 times per day) or prednisone (1 mg/kg/d tapering to 0.17 mg/kg/d) and cyclophosphamide (total dose of 9-12 g per square meter of body surface area) for 48 weeks. Outcomes Primary outcomes included complete remission, defined as proteinuria (24-hour urine protein excretion) ≤0.3 g/d, or partial remission, defined as proteinuria with protein excretion >0.3-<3.5 g/d and a 50% reduction from its peak value at 48 weeks. Secondary outcomes included serum albumin level, eGFR, doubling of serum creatinine level, end-stage renal disease, and death. Results Baseline values for proteinuria and eGFR were 5.34 ± 2.74 g/d and 84.0 ± 27.4 mL/min/1.73 m2 for the Shenqi particle group and 5.33 ± 2.47 g/d and 83.8 ± 24.9 mL/min/1.73 m2 for the control group, respectively. 132 patients (63 Shenqi particle group, 69 control group) completed the study. Change in urinary protein excretion in the Shenqi particle group was −3.01 (95% CI, −3.68 to −2.34) g/d, and in the control group, −3.28 (95% CI, −3.98 to −2.58) g/d; the mean difference between groups was 0.27 (95% CI, −0.70 to 1.23) g/d ( P = 0.6). Changes in eGFR were 12.3 (95% CI, 4.99 to 19.6) mL/min/1.73 m2 in the Shenqi particle group and −2.8 (95% CI, −10.32 to 4.77) mL/min/1.73 m2 in the control group; the mean difference between groups was 15.1 (95% CI, 4.56 to 25.55) mL/min/1.73 m2 ( P = 0.005). Severe adverse events occurred in only the control group (14.5%) and included lung infection, liver injury, and pneumonia. Limitations High rate of loss to follow-up and lack of observation period prior to the study. Conclusions Shenqi particle may be a promising alternative therapy for adults with IMN and nephrotic syndrome.
Opa-interacting protein 5 (OIP5) is a member of the cancer-testis antigen (CTA) family that elicits a spontaneous antitumor immune response. The failure of current immunotherapies for glioma has ...prompted the search for novel biomarkers that may be utilized as therapeutic targets. This study aimed to investigate whether OIP5 serves as a target for malignant glioma immunotherapy. Glioma specimens from 53 adult patients were evaluated for OIP5 expression by immunohistochemical (IHC) staining, and the correlation of OIP5 expression with World Health Organization (WHO) tumor grade was analyzed. Endogenous expression of OIP5 in glioma cell lines was determined via real-time polymerase chain reaction (RT-PCR). Using lentiviral siOIP5, the effect of OIP5 gene knockdown on proliferation, cell cycle, and apoptosis in U251 glioma cells was studied. The results show that OIP5 is overexpressed in glioma tissues and is correlated with WHO tumor grade (P < 0.001). However, OIP5 protein expression is barely detectable in normal adult brain tissues. MTT assays and analysis using the Celigo Imaging Cytometry System reveal that the silencing of OIP5 inhibits U251 cell growth. Cell cycle assays and Annexin V staining show that OIP5 silencing disrupts the balance of the cell cycle and increases U251 cell death. These results indicate that OIP5 is upregulated in malignant glioma specimens but barely detected in normal brain tissues. OIP5 knockdown inhibits the biological function of glioma cells, reinforcing that OIP5 may serve as an immunotherapeutic target for malignant glioma.
Exposure to particulate matter (PM) has been a major public health threat, but the potentially differential effects on asthma of PM remain largely unknown in high altitude settings. We evaluated the ...effects of ambient PM on asthma in high altitude settings.
The study recruited a representative sample from high altitude settings using a multistage stratified sampling procedure. Asthma was defined by a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. The annual mean PM2.5 and PM10 concentrations were calculated for each grid cell at 1-km spatial resolution based on the geographical coordinates.
We analyzed data for participants (mean age 39.1 years, 51.4% female) and 183 (3.7%, 95% confidence interval (CI): 3.2–4.2) of the participants had asthma. Prevalence was higher in women (4.3%, 95% CI 3.5–5.1) than in men (3.1%, 2.4–3.8) and increasing with higher concentration of PM exposures. For an interquartile range (IQR) difference (8.77 μg/m3) in PM2.5 exposure, the adjusted odds ratio (OR) was 1.64 (95% CI 1.46–1.83, P < 0.001) for risk of asthma. For PM10, there was evidence for an association with risk of asthma (OR 2.34, 95% CI: 1.75–3.15, P < 0.001 per IQR of 43.26 μg/m3). Further analyses showed that household mold or damp exposure may aggravate PM exposure associated risks of asthma.
This study identified that PM exposure could be a dominate environmental risk factor for asthma but largely unconsidered in the high-altitude areas. The association between PM exposure and asthma should be of interest for planners of national policies and encourage programs for prevention of asthma in residents living at high altitudes.
To study the value of circulating microRNA 216 (miR-216) as a marker for the severity of acute pancreatitis (AP) in both murine models and patients.
Mice with AP were induced by intraperitoneal ...injection of 50μg/kg/hour cerulean either 7 times, sacrificed at 8, 9, 10, 11 or 12 hours after the first injection, or 12 times, sacrificed at 24 hours after the first injection. Plasma samples and data from patients with AP were obtained from a prospective cohort. Quantitative reverse transcription polymerase chain reaction was used to determine the miR-216a and miR-216b level.
The upregulation of miR-216a and miR-216b in the serum of mice was induced by cerulean injection in both the 7- and 12-injection groups (P < 0.05). The downregulation of miR-216a in pancreatic tissues of mice with AP was detected (P < 0.05), but no difference was observed in pancreatic miR-216b levels among any of the groups (all P > 0.05). The serum miR-216a level was positively correlated with pancreatic histopathology severity scores, and was negatively correlated with pancreatic miR-216a (r = -0.483, P = 0.009). The plasma miR-216a level was significantly upregulated in patients with severe AP (SAP) compared with patients with mild AP (MAP) or moderate severe AP (MSAP) (SAP versus MAP, P = 0.04; SAP versus MSAP, P = 0.00), but no difference was seen between patients with MAP and those with MSAP (P = 0.73).
Circulating miR-216a might be a potential biomarker for the early identification of SAP.
Background
Poor pain control and opioid use are risk factors for perioperative neurocognitive disorders (PND). The peripheral nerve block (PNB) can reduce pain and opioid consumption. This systematic ...review aimed to investigate the effects of PNB on PND in older patients with hip fractures.
Methods
The PubMed, Cochrane Central Registers of Controlled Trial, Embase and ClinicalTrials.gov databases were searched from inception until November 19, 2021 for all randomized controlled trials (RCTs) comparing PNB with analgesics. The quality of the selected studies was assessed according to Version 2 of the Cochrane tool for assessing the risk of bias in RCTs. The primary outcome was the incidence of PND. Secondary outcomes included pain intensity and the incidence of postoperative nausea and vomiting. Subgroup analyses were based on population characteristics, type and infusion method of local anesthetics, and type of PNB.
Results
Eight RCTs comprising 1015 older patients with hip fractures were included. Compared with analgesics, PNB did not reduce the incidence of PND in the elderly hip fracture population comprising patients with intact cognition and those with pre-existing dementia or cognitive impairment (risk ratio RR = .67; 95% confidence interval CI = .42 to 1.08; P = .10; I2 = 64%). However, PNB reduced the incidence of PND in older patients with intact cognition (RR = .61; 95% CI = .41 to .91; P = .02; I2 = 0%). Fascia iliaca compartment block, bupivacaine, and continuous infusion of local anesthetics were found to reduce the incidence of PND.
Conclusions
PNB effectively reduced PND in older patients with hip fractures and intact cognition. When the study population included patients with intact cognition and those with pre-existing dementia or cognitive impairment, PNB showed no reduction in the incidence of PND. These conclusions should be confirmed with larger, higher-quality RCTs.
Summary Background The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed ...to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. Methods In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with125 iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov , number NCT01054274. Findings Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72–207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153–201) in the irradiation group versus 147 days (124–170) in the control group (p=0·0046). Major complications and side-effects of the treatment were severe chest pain (17 23% of 73 patients in the irradiation group vs 15 20% of 75 patents in the control group), fistula formation (six 8% vs five 7%), aspiration pneumonia (11 15% vs 14 19%), haemorrhage (five 7% vs five 7%), and recurrent dysphagia (21 28% vs 20 27%). Interpretation In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with125 iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent. Funding National High-tech Research Foundation of China, National Basic Research Program of China, Jiangsu Provincial Special Program of Medical Science, National Scientific and Technical Achievement Translation Foundation, and National Natural Science Foundation of China.
The aim of the present review was to investigate the association between the use of oral β-blockers and prognosis in patients with acute myocardial infarction (AMI) who underwent percutaneous ...coronary intervention (PCI) treatment. A systematic literature search was conducted in Pubmed (from inception to September 27, 2014) and Embase (Ovid SP, from 1974 to September 29, 2014) to identify studies that compared the outcome of patients with AMI taking oral β-blockers with that of patients not taking after PCI. Systematic review and meta-analysis were performed with random-effects model or fixed-effects model. Ten observational studies with a total of 40,873 patients were included. Use of β-blockers was associated with a reduced risk of all-cause death (unadjusted relative risk 0.58, 95% confidential interval 0.48 to 0.71; adjusted hazard ratio 0.76, 95% confidential interval 0.62 to 0.94). The potential benefit of β-blockers in preventing all-cause death was not similar in all population but was restricted to those with reduced ejection fraction, with low use proportion of other secondary prevention drugs or with non–ST-segment elevation myocardial infarction. The association between the use of β-blockers and improved survival rate was significant in ≤1-year follow-up duration. Rates of cardiac death, myocardial infarction, and heart failure readmission in patients using β-blockers were not significantly different from those in patients without β-blocker therapy. In conclusion, there is lack of evidence to support routine use of β-blockers in all patients with AMI who underwent PCI. Further trials are urgently needed to address the issue.
Background Aberrant airway epithelial remodeling is one of the cardinal histopathologic features of inflammatory airway diseases, but whether it alters the mucociliary apparatus remains unknown. ...Objective We sought to investigate the morphologic pattern of motile cilia and ciliogenesis-associated makers in hyperplastic nasal epithelium from nasal polyps (NPs) both in vivo and in vitro. Methods Biopsy specimens obtained from patients with NPs (n = 44) and inferior turbinate from healthy control subjects (n = 38) were analyzed by using scanning electron microscopy, immunofluorescence staining, single-cell (cytospin) staining, quantitative real-time PCR, and human nasal epithelial stem/progenitor cell culture and differentiation. Results Abnormal cilia architecture (untidy, overly dense, and lengthened) was more commonly observed in patients with NPs by using scanning electron microscopy. Ectopic lengthened cilia were visualized by means of immunofluorescence (patients with NPs: 6.33 μm 5.51-7.43 μm vs control subjects: 3.73 μm 3.50-4.27 μm, P < .0001), at the site of epithelial hyperplasia in isolated single cells (patients with NPs: 6.55 ± 0.23 μm vs control subjects 4.89 ± 0.24 μm, P < .0001), and in differentiated ciliated cells derived from human nasal epithelial stem/progenitor cells (patients with NPs: 9.20 ± 0.56 μm vs control subjects: 5.21 ± 0.37 μm, P < .0001). Ciliary beat frequency was found to be significantly slower in patients with NPs than control subjects in vitro . Both protein and mRNA levels of ciliogenesis-associated markers (centrosomal protein 110 CP110, forkhead box J1 Foxj1, and P73 isoform with an N-terminal transactivation domain TAp73) were significantly increased in patients with NPs versus those seen in control subjects and were positively correlated with cilia length. Conclusion For the first time, this study demonstrates for that motile cilia impairment is a co-condition of epithelial hyperplasia in patients with NPs, and this impairment of function is a likely cause of chronic mucosal inflammation or infection (eg, biofilm) observed in patients with chronic rhinosinusitis.
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