[Evaluation of safety and clinical efficacy of bilateral percutaneous kyphoplasty in treatment of osteoporotic thoraco-lumbar burst fractures].

Objective: To evaluate the safety and clinical efficacy of bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral burst fractures. Methods: It was a prospective study, 28 patients with osteoporotic thoraco-lumbar burst fractures who were treated in Beijing Chao-Yang Hospital from January 2021 to July 2021 were included, including 10 males and 18 females, with a median age of 73.6 years (range: 56.0-87.0 years). The X-ray radiographs, bone mineral density (BMD), CT three-dimensional reconstruction scan and MRI were taken and measured before operation to observe the fracture location and the posterior wall of the vertebral body, and further to determine the diagnosis. The X-ray radiographs and CT three-dimensional reconstruction scans were taken on the first day after operation and the last follow-up to observe whether there were bone cement leakage or not. The changes of kyphosis angle (KA), the height of anterior wall (HAW) and the height of posterior wall (HPW) before the operation, on the 1st day post operation and at the last follow-up were recorded. The visual analogue scale (VAS) of back pain and Oswestry dysfunction index (ODI) before the operation, 1 day post operation and at the last follow-up were used to evaluate the clinical effect of the operation. Results: All the patients were followed up for (12.2±6.0) months. The HAW on the 1st day post operation [(22.5±2.0) mm] was significantly increased as compared with that before the operation [(21.2±2.4) mm] (P<0.05). The HAW at the last follow-up [(18.9±1.6) mm] decreased signficantly as compared with that on the 1st day post opertion [(22.5±2.0) mm] (P<0.05). The HPW was also significantly corrected after surgery (P<0.05). At the end of the follow-up, the HPW [(27.2±1.3) mm] was comparable with that on the 1st day after surgery [(27.5±1.6) mm] (P>0.05). The KA on the 1st day after the operation (14.2°±1.5°) decreased significantly when compared with that before the operation (18.8°±1.3°) (P<0.05), but it was increased to 17.6°±1.4° at the last follow-up and was higher than that on the 1st day after the operation (P<0.05). There were bone cement leakage in 5 cases and adjacent vertebral fracture in 1 case. The VAS and ODI scores were all significantly lower on the 1st day and at last follow-up than that before the operation (all P<0.05). Conclusions: Bilateral PKP is effective, safe and reliable in the treatment of osteoporotic vertebral burst fracture. Careful evaluation of preoperative imaging data, accurate puncture and timing of bone cement injection are the key factors to ensure the success of the operation.

Comparison of the efficacy and safety of the EC-T (epirubicin/cyclophosphamide followed by docetaxel) and TCb (docetaxel/carboplatin) neoadjuvant regimens in early TOP2A-normal stage II-III breast cancer.

This study aimed to compare the efficacy and safety of the EC-T (4 cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 75 mg/m2) and TCb (6 cycles of docetaxel 75 mg/m2, intravenous drip (ID), day 1 + carboplatin AUC 6, ID, day 1) neoadjuvant regimens in patients with TOP2A-normal stage II-III breast cancer. This study analyzed 280 patients enrolled from three studies registered with ClinicalTrials.gov (NCT03140553, NCT03154749, NCT03507465) with early TOP2A-normal stage II-III breast cancer who received neoadjuvant chemotherapy, including 100 patients who received the EC-T regimen and 180 patients who received the TCb regimen. The primary endpoint was the ratio of RCB 0/1 (residual cancer burden 0/1) after neoadjuvant chemotherapy. The secondary endpoint was the safety of the two groups. There was no significant difference in the ratio of RCB 0/1 between the two groups (23% vs. 23.9%, p=0.614). Among the triple-negative breast cancer patients, the efficacy did not differ between the two groups (40% vs. 32%, p=0.52). Among the lymph node metastasis patients, the efficacy of the EC-T group was significantly better than that of the TCb group (14% vs. 2.6%, p=0.03). Regarding the side effects, the incidence of grade 3/4 anemia was higher in the EC-T group than in the TCb group (21.0% vs. 8.33%, p=0.002), while the incidence of grade 3/4 neutropenia was higher in the EC-T group than in the TCb group (17% vs. 14.44%, p=0.570), and the incidence of grade 3/4 thrombocytopenia was low in each group (EC-T group: 6 % and TCb group: 7.22%, p=0.697). In the EC-T group, grade 3/4 nausea and vomiting occurred in 5 patients. The EC-T group showed a higher rate of grade 3/4 myalgia than the TCb group (7% and 4.44%, respectively, p=0.363). To conclude, the TCb regimen can be used as an alternative regimen for TOP2A-normal stage II-III breast cancer patients in neoadjuvant chemotherapy. However, in patients with node-positive tumors, EC-T is still recommended. Though no difference of grade 3/4 thrombocytopenia in two groups, grade 4 thrombocytopenia caused by the carboplatin-containing regimen should be taken seriously.

Cytochrome P450 1A1 (CYP1A1) Catalyzes Lipid Peroxidation of Oleic Acid-Induced HepG2 Cells.

Nonalcoholic fatty liver disease (NAFLD) is a chronic hepatic disease associated with excessive accumulation of lipids in hepatocytes. As the disease progresses, oxidative stress plays a pivotal role in the development of hepatic lipid peroxidation. Cytochrome P450 1A1 (CYP1A1), a subtype of the cytochrome P450 family, has been shown to be a vital modulator in production of reactive oxygen species. However, the exact role of CYP1A1 in NAFLD is still unclear. The aim of this study was to investigate the effects of CYP1A1 on lipid peroxidation in oleic acid (OA)-treated human hepatoma cells (HepG2). We found that the expression of CYP1A1 is elevated in OA-stimulated HepG2 cells. The results of siRNA transfection analysis indicated that CYP1A1-siRNA inhibited the lipid peroxidation in OA-treated HepG2 cells. Additionally, compared with siRNA-transfected and benzo[a]pyrene (BaP)-OA-induced HepG2 cells, overexpression of CYP1A1 by BaP further accelerated the lipid peroxidation in OA-treated HepG2 cells. These observations reveal a regulatory role of CYP1A1 in liver lipid peroxidation and imply CYP1A1 as a potential therapeutic target.

Aprepitant plus palonosetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy.

BACKGROUND: Chemotherapy-induced nausea and vomiting remain among the most feared adverse effects for cancer patients. AIM: The aim of this study was to evaluate the efficacy and safety of a combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in patients receiving multiple-day cisplatin-based chemotherapy. METHODS: Forty-one solid cancer patients received aprepitant, palonosetron and dexamethasone during a 3-day cisplatin-based chemotherapy. Primary end-point was complete response in the overall phase (day 1 until 5 days after the end of chemotherapy). RESULTS: Aprepitant in combination with palonosetron and dexamethasone was safe, with hiccups (31.7%), fatigue (17.1%), headache (14.6%) and constipation (12.2%) the most common treatment-related adverse events, mostly mild. Complete response was seen in 58.5% of patients in the overall phase. In 23 patients receiving aprepitant in combination with palonosetron and dexamethasone more than one cycle (range: 2-5 cycles), the cumulative emetic protection rate after five cycles was 0.82. CONCLUSION: This study shows aprepitant in combination with palonosetron and dexamethasone is safe and effectively controls chemotherapy-induced nausea and vomiting in patients undergoing 3-day cisplatin-based chemotherapy, moreover, the efficacy is maintained during multiple cycles.

[Comparison of quality-of-life after proximal gastrectomy with double tract reconstruction versus gastric tube reconstruction in patients with proximal gastric cancer].

Objective: To compare the surgical safety and postoperative quality of life between proximal gastrectomy with double tract reconstruction (PG-DT) and proximal gastrectomy with gastric tube reconstruction (PG-GT) for proximal gastric cancer. Methods: This was a retrospective cohort study of clinical and follow-up data of 99 patients with proximal gastric cancer who had undergone double tract or gastric tube surgery in Nanjing Drum Tower Hospital from January 2016 to September 2021. We allocated them to two groups according to surgical procedure, namely a double tract group (PG-DT, 50 patients) and gastric tube group (PG-GT, 49 patients). Proximal gastrectomy with double tract reconstruction entails constructing a Roux-en-Y esophagojejunostomy after severing the proximal stomach, and then constructing a side-to-side anastomosis between the residual stomach and the jejunum to establish an anti-reflux barrier and thus minimize postoperative gastroesophageal reflux. Proximal gastrectomy with gastric tube reconstruction entails severing the proximal gastric stomach, constructing a tubular shaped gastric remnant, and then using a linear stapler to directly anastomose the posterior wall of the esophagus to the anterior wall of the resultant gastric tube. The primary end point was the quality of life of the two groups 1 year postoperatively (post-gastrectomy syndrome assessment scale: the higher the scores for change in body mass, food intake per meal, meal quality subscale, total physical health measurement, and total mental health measurement, the better the quality-of-life, and the higher the scores for other indicators, the worse the quality-of-life). The secondary end points were intraoperative and postoperative status, changes in nutritional status 1, 3, 6, and 12 months postoperatively, and long-term postoperative complications (gastroesophageal reflux, anastomotic stenosis, intestinal obstruction, and gastric emptying disorder 1 year postoperatively). Results: In the PG-DT group, there were 35 (70%) men and 15 (30%) women, 33 (66.0%) patients were aged <65 years, and 37 (74.0%) of them had a body mass index of 18-25 kg/m2; whereas in the PG-GT group, there were 41 (83.7%) men and eight (16.3%) women, 21 (42.9%) patients aged <65 years, and 34 (69.4%) patients with a body mass index of 18-25 kg/m2. There were no significant differences in baseline data between the two groups except for age (P=0.021). There were no significant differences in intraoperative blood loss, number of lymph node dissected, length of hospital stay, and incidence of perioperative complications between the two groups (all P>0.05). Compared with the PG-GT group, the incidence and severity of postoperative reflux esophagitis were significantly lower in the PG-DT group (4.0% [2/50] vs. 26.5% [13/49], χ2=13.507, P=0.009). The incidences of postoperative anastomotic stenosis, intestinal obstruction, and gastric retention did not differ significantly between the two groups (all P>0.05). Patients in the PG-DT group had better quality-of-life scores for esophageal reflux (2.8 [2.3,4.0] vs. 4.8 [3.8,5.0], Z=3.489, P<0.001), eating discomfort (2.7 [1.7,3.0] vs. 3.3 [2.7,4.0 ], Z=3.393, P=0.001), and total symptoms (2.3 [1.7,2.7] vs. 2.5 [2.2,2.9], Z=2.243, P=0.025) than those in the gastric tube group; The scores for postoperative symptoms (2.0 [1.0,3.0] vs. 2.0 [2.0, 3.0], Z=2.127, P=0.033), meals consumed (2.0 [1.0, 2.0] vs. 2.0 [2.0, 3.0], Z=3.976, P<0.001), work (1.0 [1.0, 2.0] vs. 2.0 [1.0, 2.0], Z=2.279, P=0.023] and daily life (1.7 [1.3, 2.0] vs. 2.0 [2.0, 2.3], Z=3.950, P<0.001) were better in the PG-DT than the PG-GT group. Patients in the PG-GT group scored better than those in the PG-DT group for somatic symptoms, such as anal evacuation (3.0 [2.0, 4.0] vs. 3.5 [2.0, 5.0], Z=2.345, P=0.019). There were no significant differences in hemoglobin, serum albumin, serum total protein, or weight loss 1 year postoperatively between the two groups (all P>0.05). Conclusions: The safety of double tract anastomosis for proximal gastric cancer is comparable to that of gastric tube surgery. Compared with gastric tube surgery, double tract anastomosis achieves less esophageal reflux and better quality of life, making it a preferable surgical procedure for proximal gastric cancer.

Benefit of inhibiting SSAO in relapsing experimental autoimmune encephalomyelitis.

We have developed several series of potent and selective small molecule inhibitors of SSAO (AOC3/VAP-1) that also block trafficking of leukocytes to sites of inflammation. Blocking of SSAO-mediated leukocyte adhesion has recently been shown efficacious in several models of inflammatory diseases. We have examined the potential of SSAO inhibitors in neurological diseases, having previously demonstrated the efficacy of SSAO inhibition in a rat model of stroke. Here we show the effect of the small molecule SSAO inhibitor LJP 1207 (IC(50) human SSAO 17 nM; ratio IC(50) SSAO:MAO >5000), on relapsing-remitting experimental autoimmune encephalomyelitis (EAE), a mouse model that shares many characteristics with human multiple sclerosis. Clinical efficacy was observed when dosing with LJP 1207 was initiated either at the peak of initial flare or during remission. These data demonstrate the potential clinical benefit of small molecule anti-SSAO therapy in this model.

Identification of a novel HLA-A allele HLA-A*2451 in a Chinese donor.

A novel human leucocyte antigen-A (HLA-A) allele, A*2451, has been identified during routine sequence-specific oligonucleotide typing and sequence-based typing of a sample from a registered donor of the Chinese Marrow Donor Program. The A*2451 allele differs from the closest matching allele A*2415 by one nucleotide substitution in exon 3, nt 363 G-->A, resulting in an amino acid change from M ATG to I ATA at codon 121.

Identification of a novel HLA-DRB1 allele (HLA-DRB1*111902*).

In this paper, we report a new HLA-DRB1 allele identified in a male acute myeloid leukaemia Chinese patient. This sample was initially typed as DRB1*11XX using commercial polymerase chain reaction-sequence-specific primers kit. When it was typed using a chip-based sequence-specific oligonucleotide technique, a novel hybridization pattern that does not match any known alleles was observed. Through sequencing, we have identified this allele as a new HLA-DRB1 allele, which was later named HLA-DRB1*111902 by the WHO Nomenclature Committee. The sequence of this new allele differs from DRB1*111901 by one nucleotide (from G to C) at 203nt of exon 2 but does not cause any amino acid substitution.

Stimulus features eliciting visual responses from neurons in the nucleus lentiformis mesencephali in pigeons.

The purpose of the present study was to find out what particular stimulus features, in addition to the direction and velocity of motion, specifically activate neurons in the nucleus lentiformis mesencephali (nLM) in pigeons. Visual responses of 60 nLM cells to a variety of computer-generated stimuli were extracellularly recorded and quantitatively analyzed. Ten recording sites were histologically verified to be localized within nLM with cobalt sulfide markings. It was shown that the pigeon nLM cells were specifically sensitive to the leading edge moving at the optimal velocity in the preferred direction through their excitatory receptive fields (ERFs). Generally speaking, nLM cells preferred black edges to white ones. However, this preference cannot be explained by OFF-responses to a light spot. The edge sharpness was also an essential factor influencing the responsive strength, with blurred edges producing little or no visual responses at all. These neurons vigorously responded to black edge orientated perpendicular to, and moved in, the preferred direction; the magnitude of visual responses was reduced with changing orientation. The spatial summation occurred in all neurons tested, characterized by the finding that neuronal firings increased as the leading edge was lengthened until saturation was reached. On the other hand, it appeared that nLM neurons could not detect any differences in the shape and area of stimuli with an identical edge. These data suggested that feature extraction characteristics of nLM neurons may be specialized for detecting optokinetic stimuli, but not for realizing pattern recognition. This seems to be at least one of the reasons why large-field gratings or random-dot patterns have been used to study visual responses of accessory optic neurons and optokinetic nystagmus, because many high-contrast edges in these stimuli can activate a neuron to periodically discharge, or groups of neurons to simultaneously fire to elicit optokinetic reflex.

Excitatory and inhibitory neurotransmitters in the nucleus rotundus of pigeons.

Rotundal neurons in pigeons (Columba livia) were examined for the effects of glutamate and its agonists NMDA and AMPA, antagonists CPP and CNQX, as well as of GABA and its antagonist bicuculline, on visual and tectal stimulation-evoked responses. Glutamate applied by iontophoresis excited all 48 rotundal cells tested, and this excitation was blocked by CNQX but not by CPP in 98% of cases, with 2% of cells being blocked by either CNQX or CPP. Out of 21 cells excited by AMPA, 20 were also excited by NMDA, indicating that AMPA and NMDA receptors may coexist in most rotundal cells. Action potentials were evoked in 36 additional cells by electrical stimulation applied to the tectum and they were also blocked by CNQX but not CPP. Visual responses recorded from a further eight luminance units and 21 motion-sensitive units were also blocked by CNQX and not CPP. On the other hand, GABA inhibited visual responses as well as responses evoked by tectal stimulation. An inhibitory period following tectal stimulation was eliminated by bicuculline. Taken together, these results indicate that glutamate may be an excitatory transmitter acting predominantly through non-NMDA receptors (AMPA receptors) in tectorotundal transmission. Meanwhile, GABA may be an inhibitory transmitter in the pigeon nucleus rotundus.

Receptive field properties of visual neurons in the avian nucleus lentiformis mesencephali.

The receptive field (RF) properties of visual neurons extracellularly recorded from the nucleus lentiformis mesencephali (nLM) in pigeons (Columba livia) were quantitatively analyzed using a workstation computer. These cells were actively spontaneous, and direction-and velocity-selective. Using spatial gratings as visual stimuli, these cells could be divided into three groups: uni- (74%), bi- (17%), and omnidirectional (9%) cells in terms of their directionality. On the basis of their velocity selectivity, they could be named slow cells (84%), preferring low velocity (0.1-11 degrees/s), and fast cells (14%), preferring rapid motion (34-67 degrees/s), with one cell (2%) responding maximally to an intermediate velocity of 18 degrees/ s. These two properties were correlated in the way that all unidirectionals were slow cells, omnidirectionals were fast cells, and bidirectionals were either slow or fast cells including the intermediate cell. Using small targets as visual stimuli, it was found that the majority of cells examined had RFs that each consisted of an excitatory RF (ERF) and an inhibitory RF (IRF) that overlapped. The unidirectionals were mainly of this type of RF structure, whereas the omnidirectionals apparently had ERFs alone. The direction preference of ERF was opposite to that of IRF for unidirectional cells tested, whereas they were perpendicular to each other for one bidirectional cell. The overall responses of these cells resulted from interaction between excitation and inhibition induced by directionally different motion. Under certain conditions, visual responses of a particular cells to a small target moving through its ERF were equal in responsive strength to those to whole-field gratings swept over the screen. It was suggested that optokinetic nystagmus produced by wholefield gratings results from population activity of large group(s) of neurons in some optokinetic nuclei, at least one of which is nLM.