PD-1/PD-L1 inhibitor monotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck: a meta-analysis.

PURPOSE: To evaluate the efficacy and safety of programmed cell death-1/programmed cell death-ligand 1 inhibitor monotherapy compared to the standard of care in the first-line setting for recurrent or metastatic head and neck squamous cell carcinoma. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library databases were searched for relevant randomized controlled trials. The clinical outcomes of overall survival, progression-free survival, objective response rates, and grade 3 or higher adverse events were analyzed using Stata SE 15 software with a significance level set to 0.05. RESULTS: We identified four randomized controlled trials (1 nivolumab, 2 pembrolizumab, and 1 durvalumab), including a total of 2474 patients. The results of the meta-analysis showed pooled hazard ratios of overall and progression-free survival for programmed cell death-1/programmed cell death-ligand 1 inhibitor monotherapy of 0.82 (95% CI: 0.73-0.91, p < 0.001) and 0.96 (95%CI: 0.84-1.07, p < 0.001) and pooled odds ratios of objective response rates and grade 3 or higher adverse events of 1.04 (95%CI: 0.46-2.37; p = 0.926) and 0.28 (95%CI: 0.22-0.35, p < 0.001), respectively. Subgroup analysis showed that inhibitors for both programmed cell death-1 (nivolumab and pembrolizumab) and programmed cell death-ligand 1 (durvalumab) were associated with significantly longer overall survival (HR = 0.80, 95% CI: 0.70-0.90, p < 0.001 and HR = 0.88, 95%CI: 0.70-1.06, p < 0.001, respectively). CONCLUSIONS: Programmed cell death-1/programmed cell death-ligand 1 inhibitor monotherapy showed more clinical benefit versus the standard of care in patients with recurrent or metastatic head and neck squamous cell carcinoma, with an acceptable safety profile.

Ameliorative effects of physcion 8-O-ß-glucopyranoside isolated from Polygonum cuspidatum on learning and memory in dementia rats induced by Aß1-40.

CONTEXT: Polygonum cuspidatum Sieb. Et Zucc. (Polygonaceae) has been traditionally used in folk medicine to treat various diseases. OBJECTIVE: This study investigates the ameliorative effects of physcion 8-O-ß-glucopyranoside (PSG) isolated from P. cuspidatum on learning and memory in dementia rats induced by Aß1-40. MATERIALS AND METHODS: Dementia rats were prepared by intracerebroventricular injection of Aß1-40. PSG (5, 10, 20, and 40 mg/kg/d, for 5 d) was administered orally. Ameliorative activity of PSG in dementia rats was evaluated by the Morris water maze (MWM) test, and its mechanisms were explored by evaluating AchE activity, levels of DA, NE, and 5-HT in hippocampus, and drebrin protein expressions in hippocampus. RESULTS: Our results indicated that PSG (5, 10, 20, and 40 mg/kg/d) significantly inhibited the prolonged latency in dementia rats (p < 0.05), and inhibitory rates were 16.5, 22.7, 33.0, and 44.8% after 5 d of learning, indicating that PSG improves learning and memory of dementia rats. Furthermore, PSG significantly decreased AchE activity (10, 20, and 40 mg/kg/d; p < 0.05), increased 5-HT (20 and 40 mg/kg/d, p < 0.05), NE (10, 20, and 40 mg/kg/d; p < 0.05), and DA levels (5, 10, 20, and 40 mg/kg; p < 0.05) in the hippocampus. Additionally, PSG obviously decreased the Aß contents in hippocampus (10, 20, and 40 mg/kg/d; p < 0.05), and up-regulated drebrin protein expressions (5, 10, 20, and 40 mg/kg/d; p < 0.05). CONCLUSIONS: PSG can significantly enhance learning and memory in Aß1-40-induced dementia rats, and the mechanisms may be related to increase levels of Ach, 5-HT, NE, and DA, decrease Aß contents, and up-regulation of drebrin proteins in hippocampus.

[Expression of HSP27 in CA1 area of hippocampus in temporal lobe epilepsy model].

OBJECTIVE: To explore the expression of heat shock protein 27 (HSP27) in the CA1 area of hippocampus in temporal lobe epilepsy (TLE) so as to elucidate the relationship between HSP27 and epileptogenesis of TLE. METHODS: The model of TLE was induced by lithium-pilocarpine in the experiment group. And the rats were further divided into the STLE and non-STLE groups based upon the absence or presence of recurrent spontaneous seizure in the next 30 days. Total protein fractions from CA1 area of hippocampus were successively obtained through tissue homogenates abstraction. The HSP27 expression in the CA1 area of hippocamp from three groups was semi-quantitatively analyzed by Western blot. And the expression of HSP27 in CA1 area was detected by pre-embedding immunogold electron microscopy. RESULTS: Expression of HSP27 in the hippocampus CA1 area as detected by Western blot was in accord with that by immunogold electron microscopy. Relative optical density values were 0.912 ± 0.011, 0.431 ± 0.011 and 0.428 ± 0.010 respectively. And gold particles were 50.0 ± 4.2, 23.0 ± 2.8 and 20.0 ± 2.3 respectively. The expression of HSP27 was the highest in the hippocampus CA1 area of the STLE group. There was statistical significance as compared with the non-STLE and normal groups (P = 0.0001). The non-STLE group was higher than the normal group. But there was no significant difference as compared with the normal group (P = 0.63). CONCLUSIONS: HSP27 in the hippocampus CA1 area may participate in the epileptogenesis of TLE.

Effect of metals on zooplankton abundance and distribution in the coast of southwestern Taiwan.

Three transects were established along the southwestern coast of Taiwan; transects from north to south were respectively extended from the Kaohsiung Harbor, Kaoping River estuary, and Fangshan River estuary. Six metals including Pb, Cd, Cr, Cu, Zn, and Ni were analyzed in the zooplankton and seawater samples. A total of 24 groups of zooplankton were identified. Calanoid was the frequently collected group and accounted for greater than 40% of the relative abundance of zooplankton. Results showed that metal concentrations in seawater close to coast were higher than those in the outside of transect. The mean of metal concentrations in zooplankton followed the hierarchy: Zn > Cu > Pb > Ni > Cr > Cd. On the whole, metal concentrations in zooplankton from sampling sites in the coastal region were observed to be higher than those in the offshore region. The bioconcentration factor of zooplankton ranged within 103-105 for all studied metals and indicated that zooplankton in the seawater of southwestern Taiwan can accumulate metal even at background concentrations of metals. The value of diversity indices exhibited an increase in the distance to the coast, whereas the abundance showed no significant correlation with that. Consequently, the lowest mean abundance of zooplankton and the highest average metal bioaccumulation were found in transect outside Kaohsiung Harbor, representing that Kaohsiung Harbor has the contamination of anthropogenic metals that results in the impact on zooplankton.

[Proteomic screening of postsynaptic density proteins related with temporal lobe epilepsy].

OBJECTIVE: To explore the postsynaptic density (PSD) proteins related with the development of temporal lobe epilepsy (TLE). METHODS: Five SD rats were injected intra-peritoneally with lithium chloride and then pilocarpine twice to establish epilepsy models. At last 24 rats developed TLE, and 12 developed non-TLE. Then rats underwent intraperitoneal injection of normal saline (Norm group). Thirty days after the appearance of epilepticus the rats were decapitated with their brains taken out. The PSD proteins were extracted and purified by using sucrose gradient centrifugation and membrane sequence extraction, isolated by using two-dimensional gel electrophoresis. PDQuest software was used to screen the specifically and differentially expressed protein spots. Partial differentially expressed PSD protein spots were selected and identified by MALDI-TOF-MS. Several identified proteins were detected in the PSD fraction by Western blotting. RESULTS: Compared with the non-TLE and Norm groups, there were 40 differential protein spots in the TLE group. The expression levels of heat shock protein-27 (HSP-27), fructose-bisphosphate aldolase A (FBA), creatine kinase (CK), thyroid receptor-interacting protein 6 (TRIP6), myelin basic protein S (MBP), and LIM domain were up-regulated, but the expression levels of tubulin, actin, internexin-alpha, peptidyl-prolyl cis-trans isomerase (PPIase), sorting nexin 3 (SNX3), aconitate hydratase (ACO), glyceradehydea-3-phosphate dehydrogenase (GADPH), and succinate-coenzyme A ligase (SCOAL) were down-regulated in the TLE group. The HSP27, tubulin-alpha, and SNX3 were in the PSD gels were immunostaining positive in the 3 groups. CONCLUSION: The differential expression of PSD proteins in TLE may be due to injury induced neural plasticity. But the degree thereof may contribute to the development of TLE. These identified proteins can be regarded as important candidates for or against the development of TLE.

Effects of problem-oriented willed-movement therapy on motor abilities for people with poststroke cognitive deficits.

BACKGROUND AND PURPOSE: Cognitive deficits after stroke are common and interfere with recovery. One purpose of this study was to determine whether the motor abilities of subjects who have poststroke cognitive deficits and who have received problem-oriented willed-movement (POWM) therapy will improve more than the motor abilities of subjects in the reference group who have received neurodevelopmental treatment (NDT). Another purpose of this study was to identify the relationship between cognitive function and motor abilities for both groups. SUBJECTS: The subjects recruited for this study were 36 men and 11 women with various degrees of poststroke cognitive deficits. METHODS: A randomized block design was used to assign the subjects to 2 groups. Cognitive function and motor ability were evaluated with the Mini-Mental State Examination and the Stroke Rehabilitation Assessment of Movement (STREAM). Both groups received physical therapy 5 or 6 times per week in 50-minute sessions. RESULTS: The STREAM scores improved after treatment in both groups. Main group effects were found for the lower-extremity (F=4.58, P< .05) and basic mobility (F=27.49, P< .01) subscales of the STREAM. Pretest cognitive function showed a positive relationship with posttest motor ability in the NDT group (r = .446, P< .05). However, the relationship between pretest cognitive function and posttest motor ability had no statistical significance in the POWM group (r = .101, P= .630). DISCUSSION AND CONCLUSION: These findings suggest that, regardless of a person's cognitive function, POWM intervention is effective in improving lower-extremity and basic mobilities and indicates the need to use relatively intact cognitive function or perceptual function, or both, to improve motor rehabilitation for people with cognitive function deficits.

Aetiology of epilepsy in surgically treated patients in China.

The aim of this retrospective, multicenter clinical study was to evaluate the aetiology of epilepsy in surgically treated patients in China. The detailed clinical records of all intractable partial epilepsy (IPE) were reviewed in five tertiary referral centres from June 1991 to June 2000. 1650 patients (927 males, 723 females) were recruited. 41.4% had aetiological factors, including the histories of major brain trauma (20.9%), febrile seizure (6.5%), meningitis (5.4%), encephalitis (5.0%), prenatal distress (2.1%), birth trauma (0.8%) and family history of seizure (0.7%). The pathological lesions were divided into eight groups according to the nature of the lesion: scar (19.2%), vascular malformations (VM) (17.7%), hippocampal sclerosis (HS) (16.2%), tumours (15.0%), gliosis (12.1%), neuronal migration disorders (NMDs) (7.4%), intracranial infection (4.5%), and other lesions (7.9%). In conclusion, effective management of these aetiological factors and pathological lesions may be essential to deal with IPE. Scar, HS, VM, NMDs are the most likely consequences of antecedent morbid events.

Surgical treatment of thoracic esophageal carcinoma: report of 326 cases.

OBJECTIVE: To review our experience in surgical treatment of 326 cases of thoracic esophageal carcinoma. METHODS: The clinical data of 326 patients with thoracic esophageal carcinoma from January 1990 to January 2001 were analyzed retrospectively. Among the 326 patients, the lesions of 32 patients were identified in the upper thoracic segment of the esophagus, and were found in the middle segment in 213 cases with the left 81 cases having lesions in the lower segment. Left cervical esophagogastrostomy was performed through triple incision (left cervical, right thoracic and abdominal) in 79 cases. Esophagocolostomy through triple incision was performed in 5 cases. Another 156 patients received left cervical esophagogastrostomy through two incisions (left cervical and left thoracic). Supra-aorticarch esophagogastrostomy through left posterola- teral thoracotomy was performed in 53 cases, and sub-arch esophagogastrostomy through left posterolateral thoracotomy in 33 cases. RESULTS: The post-operative mortality was 1.23% (4/326), with a five-year survival rate of 35.3%. CONCLUSION: Subtotal esophagectomy combined with thorough lymph node dissection can be the first choice for thoracic esophageal carcinoma to improve the postoperative survival rate and the quality-of life-of the patients.