Pharmacotherapies for Central Post-Stroke Pain: A Systematic Review and Network Meta-Analysis.

Background: Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown. Aim: The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis. Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs. Results: Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31; P - score = 0.93), prednisone (SMD -2.38, 95% CI -3.09 to -1.67; P - score = 0.92), levetiracetam (SMD -2.11, 95% CI -2.97 to -1.26; P - score = 0.87), lamotrigine (SMD -1.39, 95% CI -2.21 to -0.58; P - score = 0.73), etanercept (SMD -0.92, 95% CI -1.8 to -0.03; P - score = 0.59), and pregabalin (SMD -0.46, 95% CI -0.71 to -0.22; P - score = 0.41) had significantly better treatment effect. Pamidronate, prednisone, and levetiracetam ranked as the first three most effective treatments. In subgroup analyses, prednisone, levetiracetam, lamotrigine, and pregabalin were more effective than placebo as oral pharmacotherapies, while etanercept was more effective than placebo as injectable pharmacotherapy. Conclusions: Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.

Immune Microenvironment in Langerhans Cell Histiocytosis: Potential Prognostic Indicators.

In this study, the immune microenvironment in Langerhans cell histiocytosis (LCH) was characterized to determine if immune indices are predictive of severity. Serum samples from 54 treatment-naïve patients were analyzed quantitatively for inflammatory cytokines and immunoglobulins before and after the induction of chemotherapy. The initial serum sIL-2R, TNF-α, and IL-10 of untreated LCH patients with risk organ involvement (RO+) were significantly higher than those with single-system (SS) involvement. LCH patients with hematologic involvement exhibited a significantly higher sIL-2R, TNF-α, IL-10, and IL-1ß expression, as compared to the group without involvement. sIL-2R, TNF-α, and IL-10 were increased in patients with liver or spleen involvement. Th cells have decreased in the liver+ and spleen+ group, and Ts cells were significantly decreased in non-response group after induction chemotherapy. The serum level of immune indices represents, to some extent, the severity of the disease. Pertinent laboratory inspections can be used to improve risk stratification and guide immunotherapy.

Chinese Siblings with Prader-Willi Syndrome Inherited from Their Paternal Grandmother.

BACKGROUND: Prader-Willi syndrome (PWS) is a complex neurobehavioral disorder caused by failure of expression of paternally inherited genes in the PWS region of chromosome 15. CASE CHARACTERISTICS: Two siblings who both met the inclusion criteria for clinical diagnosis of PWS during neonatal period. OUTCOME: Molecular genetic analysis demonstrated a 417-kb microdeletion within the 15q11.2 region inherited from siblings' paternal grandmother, involving key genes of PWS, except for UBE3A, which may explain why their father and paternal grandmother had a normal phenotype. CONCLUSION: The findings may be helpful for better understanding of the underlying mechanism of this rare imprinting defect.

Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes.

Background To investigate the clinical and molecular characteristics of Chinese children with maturity onset diabetes of the young (MODY). Methods A total of 42 Chinese patients suspected MODY referred to our unit from 2014 to 2018 were enrolled. Mutational analysis of monogenic diabetes mellitus genes was performed by next-generation sequencing and confirmed by Sanger sequencing. Results There were 28 males (66.7%) and 14 females (33.3%) with a mean age of 9.49 ± 3.46 years (range, 1.4-15.3 years) and a mean birth weight of 3.38 ± 0.49 kg (range, 2.55-4.90 kg). Among these patients, 15 patients had polyuria, polydipsia or weight loss. Two patients (4.8%) were obese and six (14.3%) were overweight. Moreover, 13 patients (30.9%) had a family history of diabetes. Thirty variants were identified in 28 patients. Twenty-six variants in 25 patients were pathogenic or likely pathogenic genes (59.5%, 25/42), including 15 patients (60.0%, 15/25) with GCK mutation, four (16.0%, 4/25) with PAX4 mutation, three (12.0%, 3/25) with HNF4A mutation, one (4.0%, 1/25) with INS mutation, one (4.0%, 1/25) with NEUROD1 mutation and one (4.0%, 1/25) with HNF1A mutation. Nine mutations (36.0%, 9/25) were novel. There was no difference between mutation-suspected patients and MODY-confirmed patients except for a 2-h glucose increment in an oral glucose tolerance test (OGTT), while the GCK-MODY had lower glycated hemoglobin (HbA1c) and a significantly smaller 2-h glucose increment in an OGTT compared with transcription factor MODYs. The GCK-MODY was identified by incidental hyperglycemia without glycosuria. GCK-MODY without drug management and hepatocyte nuclear factor-1 alpha (HNF4A) or HNF1A-MODY with sulfonylurea therapy obtained good glucose controlling. Conclusions Mutation of the GCK gene is the most common in MODY patients in China followed by PAX4. The screening criteria can improve the cost-effectiveness of disease diagnosis and treatment. A precise molecular diagnosis would lead to optimal treatment of the patients.

Elevated tumour necrosis factor-alpha was associated with intima thickening in obese children.

AIM: This study investigated the relationship between intima-media thickness (IMT) and immune parameters in obese children from five to 16 years of age. METHODS: We enrolled 185 obese children with a mean age of 10.65 ± 2.10 years and 211 controls with a mean age of 10.32 ± 1.81 years. Glycometabolism, lipid metabolism, sex hormones, immune indices and carotid IMT were measured. RESULTS: Serum interleukin (IL)-6, IL-10, tumour necrosis factor (TNF)-alpha, white blood cells and common and internal carotid artery IMTs in the obese group were higher than those in the control group (p < 0.05, respectively). Bivariate correlation analysis showed that the common carotid arterial IMT was positively correlated with alanine aminotransferase, triglyceride, uric acid, apolipoprotein B, IL-6, IL-10, TNF-alpha, follicle-stimulating hormone and testosterone. Internal carotid artery IMT was positively correlated with alanine aminotransferase and follicle-stimulating hormone. Both common and internal carotid artery IMTs were inversely correlated with apolipoprotein A1 (p < 0.05, respectively). Stepwise multiple regression analysis showed that testosterone, alanine aminotransferase and TNF-alpha were the independent determinants of common carotid arterial IMT. CONCLUSION: Tumour necrosis factor-alpha, alanine aminotransferase and testosterone were associated with intima thickening in the early life in obese children and may increase later risks of premature atherogenicity and adult cardio-cerebrovascular diseases.

An optically pumped XeF(C-A) laser with repetitive rate of 10 Hz.

A novel XeF(C-A) laser which can be operated in repetition mode has been developed based on surface discharge optical pumping technique. Its maximum repetitive rate is up to 10 Hz. The influence of repetitive rate and gas flow rate on the stability of output energy is studied and the main factor which influences the stability of output energy is analyzed. The experimental results show that increasing the gas flow rate into laser chamber can improve the stability of the output energy. The ideal output energy results of 20 laser pulses under different repetitive rates and their optimal experimental conditions are presented. Output energies of more than 4 J and better stability can be obtained when the laser device operates at 1, 2, and 5 Hz, respectively. When the gas feed rate is larger than 53 l/s, the stability of output energy is improved obviously at the repetitive rate of 10 Hz, and the average energy of 20 laser pulses is up to 3.2 J.

PEG-rhGH therapy for small for gestational age rats and effects on their metabolic parameters.

AIMS: To determine whether administration of long-acting polyethylene glycol moiety covalently linked to recombinant human growth hormone (PEG-rhGH) can be efficacious in the treatment of small for gestational age (SGA) rats and to characterize its effects on metabolic parameters. METHODS: 20 pregnant rats were randomly divided into undernourished and standard nourished groups. SGA or appropriate for gestational age (AGA) offspring from each were then randomly assigned to receive either PEG-rhGH or normal saline (NS). Once-weekly subcutaneous injections of PEG-rhGH (2 µg/g/week) were administered starting at 21-42 days. Glycometabolism, blood pressure (BP), hormone and biochemical levels were analyzed at 21, 42 and 70 days. RESULTS: SGA rats at 21 days were lighter and shorter than AGAs (34.77 ± 2.11 vs. 48.83 ± 1.78 g, 10.42 ± 0.22 vs. 12.99 ± 0.17 cm, p < 0.05). At 42 days, SGA animals experienced a greater body weight gain. BP was higher in NS-treated SGA than in the AGA group at 70 days (138.16 ± 3.02 vs. 112.26 ± 5.42 mm Hg, p < 0.05). Meanwhile, NS-treated SGA exhibited higher glucose levels at 60 and 90 min than the AGA groups. No differences in hormone levels between the SGA and AGA groups were found at the end of PEG-rhGH treatment. CONCLUSION: These data suggest that PEG-rhGH treatment does not increase the risk of developing metabolic syndrome in adolescent aged rats.