Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Applications of inverse opal photonic crystal hydrogels in the preparation of acid-base color-changing materials.

Hydrogels are three-dimensional (3D) crosslinked network hydrophilic polymers that have structures similar to that of biological protein tissue and can quickly absorb a large amount of water. Opal photonic crystals (OPCs) are a kind of photonic band gap material formed by the periodic arrangement of 3D media, and inverse opal photonic crystals (IOPCs) are their inverse structure. Inverse opal photonic crystal hydrogels (IOPCHs) can produce corresponding visual color responses to a change in acid or alkali in an external humid environment, which has wide applications in chemical sensing, anti-counterfeiting, medical detection, intelligent display, and other fields, and the field has developed rapidly in recent years. In this paper, the research progress on fast acid-base response IOPCHs (pH-IOPCHs) is comprehensively described from the perspective of material synthesis. The technical bottleneck of enhancing the performance of acid-base-responsive IOPCHs and the current practical application limitations are summarized, and the development prospects of acid-base-responsive IOPCHs are described. These comprehensive analyses are expected to provide new ideas for solving problems in the preparation and application of pH-IOPCHs.

RNA sequencing and proteomic profiling reveal alterations by MPTP in chronic stomach mucosal injury in tree shrew Chinese (Tupaia belangeri chinensis).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that can cause gastrointestinal ulcers by affecting dopamine levels. Therefore, MPTP has been considered a toxic substance that causes gastric ulcer disease in experimental animals. In this study, tree shrews were used as the animal model of gastric mucosa injury, and MPTP was intraperitoneally injected at a lower MPTP dosage 2 mg/kg/day for 13 weeks, while tree shrews were not injected as the control group. Under the light microscope, local congestion or diffuse bleeding points of gastric mucosa and multiple redness and swelling bleeding symptoms on the inner wall were observed in the treatment group, as well as immune cell infiltration was found in HE staining, but no such phenomenon was observed in the control group. In order to explore the molecular basis of changes in MPTP induced gastric mucosa injury, the transcriptome and proteome data of gastric mucosa were analyzed. We observed significant differences in mRNA and protein expression levels under the influence of MPTP. The changes in mRNA and proteins are related to increased immune infiltration, cellular processes and angiogenesis. More differentially expressed genes play a role in immune function, especially the candidate genes RPL4 and ANXA1 with significant signal and core role. There are also differentially expressed genes that play a role in mucosal injury and shedding, especially candidate genes GAST and DDC with certain signaling and corresponding functions. Understanding the factors and molecular basis that affect the expression of related genes is crucial for coping with Emotionality gastric mucosa injury disease and developing new treatment methods to establish the ability to resist disease.

Vector-Mediated Cancer Gene Therapy Reduces Toxicity and Inhibition of Lung Carcinoma Growth in Nude Mice.

Replication-competent oncolytic adenovirus (TOA2) gene therapy is a recently introduced anti-tumor treatment regimen with superior results. The biodistribution studies of virus vector-based medicine seem more cautious and have been given much attention recently in terms of its quality and safety in preclinical trials. The current study determined the biodistribution and safety of a replication-competent adenovirus in different organs to predict its toxicity threshold. The present study has used TOA2, while biodistribution analysis was performed in human lung carcinoma A549-induced tumor-bearing nude mice model. Intratumoral injection was applied onto tumor-bearing mice with the adenovirus (3×1010 VP per mouse). Mice were sacrificed at the end of the experiment and the organs were dissected. Biodistribution analysis was done with complete hexon gene detection in each organ using quantitative real-time polymerase chain reaction (qRT-PCR). The biodistribution and concentration profiles showed that the TOA2 is well distributed in the entire tumor tissue. After dose 3 at day 11, the concentration of the virus has increased in the tumor tissue from 2240.54 (± 01.69) copies/100 ng genome to 13,120.28 (± 88.21) copies/100 ng genome on the 18th day, which eventually approached 336.45 (± 23.41) copies/100ng genome on the day 36. On the contrary, the concentration of the same decreased in the order of the liver, kidney, spleen, lung, and heart over time but no distributional traces in gonads. But the concentration found decreased dramatically in blood and other organs, while at the end of the experiment no detectable distribution was seen besides tumor tissue. The study confirms that adenovirus-based tumor therapy using conditionally replicating competent oncolytic TOA2 exhibited great efficiency with no toxicity at all.

Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

Prediction and Effect Verification of Thiamine as a Leveling Agent in Chip Wafer Electroplating.

Thiamine, a nitrogen-containing heterocyclic compound, is explored for the first time as a novel leveling agent in this study. Based on the density functional theory (DFT) calculations and molecular dynamics (MD) simulations of the adsorption process of thiamine and the commonly used leveling agent JGB, the average values of the binding energies after equilibrium of thiamine and JGB are similar, which indicates that the thiamine molecules have strong bonding ability with the surface of copper and can be adsorbed tightly on the surface of copper. By cyclic voltammetry (CV) curve, thiamine was found to inhibit copper deposition and the inhibition effect was stronger than JGB. The chrono potential curve (CP) test found that the potential difference △η = 87 > 50 mV at high and low speeds of thiamine, which indicates that thiamine has the potential to be used as a leveling agent. Electrochemical impedance spectroscopy (EIS) testing found that thiamine inhibited copper precipitation by inhibiting the reactions of Cu2+ → Cu+ and Cu+ → Cu. According to electroplating experiments, thiamine has a leveling effect on wafer electroplating and can be used as a leveling agent because the copper layer on the wafer obtained by adding it has a smoother surface compared to the copper layer obtained without adding it. It was found that wafer electroplating does not require PEG, and only adding 55 mg/L Cl-, 6 mg/L SPS, and 4 mg/L thiamine as additives can achieve a good filling effect.

Early versus delayed mobilization for arthroscopic rotator cuff repair (small to large sized tear): a meta-analysis of randomized controlled trials.

BACKGROUND: The timing to start passive or active range of motion (ROM) after arthroscopic rotator cuff repair remains unclear. This systematic review and meta-analysis evaluated early versus delayed passive and active ROM protocols following arthroscopic rotator cuff repair. The aim of this study is to systematically review the literature on the outcomes of early active/passive versus delayed active/passive postoperative arthroscopic rotator cuff repair rehabilitation protocols. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) published up to April 2022 comparing early motion (EM) versus delayed motion (DM) rehabilitation protocols after arthroscopic rotator cuff repair for partial and full-thickness tear was conducted. The primary outcome was range of motion (anterior flexion, external rotation, internal rotation, abduction) and the secondary outcomes were Constant-Murley score (CMS), Simple Shoulder Test Score (SST score) and Visual Analogue Scale (VAS). RESULTS: Thirteen RCTs with 1,082 patients were included in this study (7 RCTs for early passive motion (EPM) vs. delayed passive motion (DPM) and 7 RCTs for early active motion (EAM) vs. delayed active motion (DAM). Anterior flexion (1.40, 95% confidence interval (CI), 0.55-2.25) and abduction (2.73, 95%CI, 0.74-4.71) were higher in the EPM group compared to DPM. Similarly, EAM showed superiority in anterior flexion (1.57, 95%CI, 0.62-2.52) and external rotation (1.59, 95%CI, 0.36-2.82), compared to DAM. There was no difference between EPM and DPM for external rotation, retear rate, CMS and SST scores. There was no difference between EAM and DAM for retear rate, abduction, CMS and VAS. CONCLUSION: EAM and EPM were both associated with superior ROM compared to the DAM and DPM protocols. EAM and EPM were both safe and beneficial to improve ROM after arthroscopic surgery for the patients with small to large sized tears.

Biomechanical evaluation of a novel atlas polyaxial transverse connecting screw system, an in vitro human cadaveric study.

PURPOSE: To introduce a novel transverse connecting screw system, and to evaluate the biomechanical stability of the novel screw system using human cadaveric specimens. METHODS: Six fresh-frozen cadaveric upper cervical spines were used in our study. Every specimen was tested under 5 conditions: intact group; unstable group; C1 to C2 screw rod system group; C1 to C2 + crosslink system group; atlas polyaxial transverse connecting screw (APTCS) system. RESULTS: Compared with the intact state, C1 to C2 screw rod system, C1 to C2 + CL system and APTCS showed statistically decrease range of motion in all directions except for the unstable group under posterior extension direction (P < .05). APTCS group has the least range of motion in all directions (P < .001). CONCLUSION: The APTCS system was able to restore stability to the atlantoaxial joint. APTCS system has the advantages of easy installation, convenient bone grafting, and strong biomechanical strength.

The native reed-specific bird, reed parrotbill, has been detected in exotic smooth cordgrass.

After the smooth cordgrass Spartina alterniflora invaded coastal China, native birds started avoiding the green desert, and bird diversity declined. After many years, a few passerine birds began to enter and use smooth cordgrass, but only birds with a nonspecialised habitat. In this study, we found that a native reed-specific bird, the parrotbill Calamornis heudei, flocked and sang in a smooth cordgrass habitat throughout the overwintering period near Sheyang Port in Yancheng, Jiangsu Province. This observation suggests that native obligate birds may be forced to adapt to exotic smooth cordgrass habitats after long-term coexistence, which would, obviously, affect the distribution, feeding and reproduction of birds. The concern is that this could be an ecological trap, leading to unknown consequences. More research is required to examine the process occurring along the Chinese coast.

Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.

The long-term neurodevelopmental outcomes of febrile seizures and underlying mechanisms.

Febrile seizures (FSs) are convulsions caused by a sudden increase in body temperature during a fever. FSs are one of the commonest presentations in young children, occurring in up to 4% of children between the ages of about 6 months and 5 years old. FSs not only endanger children's health, cause panic and anxiety to families, but also have many adverse consequences. Both clinical and animal studies show that FSs have detrimental effects on neurodevelopment, that cause attention deficit hyperactivity disorder (ADHD), increased susceptibility to epilepsy, hippocampal sclerosis and cognitive decline during adulthood. However, the mechanisms of FSs in developmental abnormalities and disease occurrence during adulthood have not been determined. This article provides an overview of the association of FSs with neurodevelopmental outcomes, outlining both the underlying mechanisms and the possible appropriate clinical biomarkers, from histological changes to cellular molecular mechanisms. The hippocampus is the brain region most significantly altered after FSs, but the motor cortex and subcortical white matter may also be involved in the development disorders induced by FSs. The occurrence of multiple diseases after FSs may share common mechanisms, and the long-term role of inflammation and γ-aminobutyric acid (GABA) system are currently well studied.

Metal-Organic Framework-Derived Homologous Sulfide Heterojunction for Robust Enzyme-Like Self-Driven Bacteria-Killing through Enhanced Electron Transfer.

Infectious diseases caused by various bacteria pose a serious threat to human health, and the emergence of drug-resistant bacteria has forced humans to develop new and effective antimicrobial agents and strategies. Herein, a metal-organic framework-derived Bi2 S3 /FeS2 heterojunction (BFS) is synthesized, and the materials-microorganism interface is further constructed. Through interfacial electron transfer, electrons are transferred from the bacteria to the BFS surface, disrupting the balance of the bacterial electron transport chain and inhibiting the metabolic activity of the bacteria. Moreover, BFS has enzyme-like (oxidase and peroxidase) properties and can produce a large amount of reactive oxygen species to kill additional bacteria. In vitro antibacterial results show that the antibacterial efficiency of BFS against both Staphylococcus aureus and Escherichia coli reaches more than 99.9% after 4 h of co-culture under dark conditions. Meanwhile, in vivo experiments show that BFS can effectively kill bacteria and promote wound healing. This work shows that BFS could be a novel, effective nanomaterial for the treatment of bacterial infections by constructing the materials-microorganism interface.

A summary of the current diagnostic methods for, and exploration of the value of microRNAs as biomarkers in, sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is an acute neurological deficit caused by severe sepsis without signs of direct brain infection, characterized by the systemic inflammation and disturbance of the blood-brain barrier. SAE is associated with a poor prognosis and high mortality in patients with sepsis. Survivors may exhibit long-term or permanent sequelae, including behavioral changes, cognitive impairment, and decreased quality of life. Early detection of SAE can help ameliorate long-term sequelae and reduce mortality. Half of the patients with sepsis suffer from SAE in the intensive care unit, but its physiopathological mechanism remains unknown. Therefore, the diagnosis of SAE remains a challenge. The current clinical diagnosis of SAE is a diagnosis of exclusion; this makes the process complex and time-consuming and delays early intervention by clinicians. Furthermore, the scoring scales and laboratory indicators involved have many problems, including insufficient specificity or sensitivity. Thus, a new biomarker with excellent sensitivity and specificity is urgently needed to guide the diagnosis of SAE. MicroRNAs have attracted attention as putative diagnostic and therapeutic targets for neurodegenerative diseases. They exist in various body fluids and are highly stable. Based on the outstanding performance of microRNAs as biomarkers for other neurodegenerative diseases, it is reasonable to infer that microRNAs will be excellent biomarkers for SAE. This review explores the current diagnostic methods for sepsis-associated encephalopathy (SAE). We also explore the role that microRNAs could play in SAE diagnosis and if they can be used to make the SAE diagnosis faster and more specific. We believe that our review makes a significant contribution to the literature because it summarizes some of the important diagnostic methods for SAE, highlighting their advantages and disadvantages in clinical use, and could benefit the field as it highlights the potential of miRNAs as SAE diagnostic markers.

To explore the change of motor cognitive function in pituitary tumor rats after operation.

To study the changes of motor and cognitive function of pituitary tumor rats after the operation. Methods: The experiment was divided into three groups: control group, model group and operation group (30 animals for each group). Female Fischer344 rats were selected. Model group rats were subcutaneously embedded with 10 mg estrogen sustained-release pump to induce a pituitary tumor model, and control group rats were subcutaneously embedded with a normal saline sustained-release pump as control. The operation group was successfully treated by microsurgery after the model was established. The quantitative expressions of PTTG, FGF-2 and VEGF were detected by Western blot. Morris test was used to detect the spatial learning and memory ability of rats. Western blot results showed that compared with the model group, the expression of the operation group was decreased, but still higher than that of the control group (p < 0.05). The water maze test results showed that the incubation period of searching the safe island in the model group was significantly longer than that in the control group on the 8th and 9th day after the injury, and the difference was statistically significant (p < 0.05). The incubation period of searching the safe island on the 8th and 9th day after injury in the operation group was significantly shorter than that in the control group. Through the detection of behavioral-related experimental and protein, the motor memory of rats after pituitary tumor surgery can be improved to some extent.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer: a single-center, single-arm, prospective Phase II trial (PKUCH-R02).

Background: Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. Methods: This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Results: Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. Conclusions: For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

Effect of ß1-adrenergic receptor gene polymorphism on ventricular arrhythmia and prognosis after myocardial infarction.

BACKGROUND: Ventricular arrhythmia is a common complication of acute myocardial infarction (AMI). The Arg389Gly polymorphism of the ß1-adrenergic receptor genotype may affect AMI patients. METHOD: Patients diagnosed with AMI were included in this study. Clinical data were obtained from the patient's medical history, and genotypes were retrieved from laboratory test reports. ECG data were recorded daily. Data analysis was performed using SPSS 20.0, and differences were deemed statistically significant at P  < 0.05. RESULT: In the final study, 213 patients were included. The proportions of the Arg389Arg, Arg389Gly, and Gly389Gly genotypes were 65.7%, 21.6%, and 12.7%, respectively. Patients with the Arg389Arg genotype exhibited significantly elevated cardiac troponin T (cTnT) and pro-BNP levels compared to the Arg389Gly and Gly389Gly genotypes [cTnT: 4.00 ±â€…2.43 ng/ml versus 2.82 ±â€…1.82 ng/ml, P  = 0.012; pro-BNP: 1942.37 (1223.194, 206.59) pg/ml versus 1604.57 (798.05, 1884.79) pg/ml, P  = 0.005]. Patients with the Arg389Arg genotype exhibited a lower ejection fraction than those with the Gly389Gly genotype (54.13 ±â€…4.94% vs. 57.11 ±â€…2.87%, P  < 0.001). Patients homozygous for Arg389Arg exhibited a higher incidence of ventricular tachycardia and a greater proportion of premature ventricular contraction (PVC) compared to patients homozygous for Gly389Gly (ventricular tachycardia: 19.29% vs. 0.00%, P  = 0.009; PVC: 70.00% vs. 40.74%, P  = 0.003). CONCLUSION: The Arg389Arg genotype is associated with greater myocardial damage, impaired cardiac function, and an increased probability of ventricular arrhythmia in AMI patients.

Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer: Findings From a Prospective Phase 2 Trial (PKUCH-R01 Trial, NCT02860234).

OBJECTIVE: To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer. BACKGROUND: Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested. METHODS: This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate. RESULTS: Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively. CONCLUSIONS: Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.

Clinical advantages of absorbable barbed wires in laparoscopy combined with choledochoscopy treatment of gallbladder polyps / 中国基层医药

Objective:To investigate the clinical advantages of absorbable barbed wires in laparoscopy combined with choledochoscopy treatment of gallbladder polyps.Methods:The clinical data of 103 patients with gallbladder polyps who received laparoscopy combined with choledochoscopy treatment in The First People's Hospital of Lianyungang from February 2016 to March 2018 were retrospectively analyzed. Sixty-five patients in the observation group underwent gallbladder wall sutures with absorbable barbed wires, and thirty-eight patients in the control group underwent gallbladder wall sutures with common absorbable wires. The operative time, gallbladder wall suture time, intraoperative blood loss, average hospitalization time, and postoperative bile leakage were compared between the two groups.Results:There were no significant differences in intraoperative blood loss and average hospitalization time between the two groups ( P = 0.312, P = 0.114). In the observation group, gallbladder wall suture time and operative time were (5.58 ± 1.14) minutes and (60.71 ± 11.03) minutes, respectively, which were shorter than (6.32 ± 1.04) minutes and (68.24 ± 9.61) minutes in the control group ( t = 3.23, 3.50, P = 0.002, 0.001). No bile leakage occurred in the observation group and bile leakage occurred in four (10.5%) patients in the control group. There was a significant difference in bile leakage between the observation and control groups ( χ2 = 4.57, P = 0.032). Conclusion:Absorbable barbed wires for gallbladder wall sutures during operation in laparoscopy combined with choledochoscopy treatment of gallbladder polyps is safe and feasible. It can markedly shorten gallbladder wall suture time and operative time, decrease the incidence of bile leakage, and has a clinical advantage over common absorbable wires.

Anesthetic Management and Outcomes of Endovascular Treatment of Basilar Artery Occlusion: Results From the ATTENTION Registry / 대한뇌졸중학회지

Background@#and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. @*Methods@#This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. @*Results@#Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). @*Conclusion@#In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

Study on the inhibitory effect of UBE2T on radiosensitivity of lung adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.