Mouse model of Graves' orbitopathy induced by the immunization with TSHR A and IGF-1R α subunit gene.

PURPOSE: The study aimed to establish a mouse model of Graves' disease (GD) with Graves' orbitopathy (GO; GD + GO) that can represent the clinical disease characteristics. METHODS: A eukaryotic expression plasmid of insulin-like growth factor 1 receptor (IGF-1R) α subunit (pcDNA3.1/IGF-1Rα) and a thyrotropin receptor (TSHR) A subunit plasmid (pcDNA3.1/TSHR-289) were injected in female BALB/c mice followed by immediate electroporation to induce a GD + GO model. Grouping was performed according to the frequency of injection (2- to 4-week intervals) and type of injected plasmids: T: pcDNA3.1/TSHR-289( +), I: pcDNA3.1/IGF-1Rα( +), or co-injection T + I: pcDNA3.1/TSHR-289( +) and pcDNA3.1/IGF-1Rα( +). Serum TSH, T4, TSAb, TSBAb, body weight, and blood glucose levels were evaluated. Thyroid 99mTcO4- imaging and retrobulbar magnetic resonance imaging (MRI) were performed, and bilateral eye muscle volumes were measured. Immunohistochemistry and hematoxylin-eosin staining were performed on the relevant tissues, and semi-quantitative analysis was performed. RESULTS: A total of 60% of mice (3/5, one mouse died) in the T group developed GD + GO. In the T + I group, 83.3% of mice (5/6) developed GD + GO. Mice in the I group did not develop GD. Compared with the control group, serum T4, TSAb, and TSBAb of the mice in the GD + GO model groups were increased to varying degrees (P < 0.05), and serum TSH and body weight were significantly lower compared to the control group (P < 0.05). The thyroid uptake capacity of 99mTcO4- and the volume of eye muscle of mice in the GD + GO group were significantly higher compared to the control group (P < 0.05). The thyroid and retrobulbar muscles of these mice showed varying inflammatory infiltration and interstitial muscle edema. The severity of GD + GO in the co-injection group was not related to injection frequency; however, GD and ocular signs in co-injection mice were more severe compared to the T group. CONCLUSIONS: We successfully induced a GD + GO mouse model by a repeated co-injection of pcDNA3.1/IGF-1Rα and pcDNA3.1/TSHR-289 plasmids. Injection of pcDNA3.1/IGF-1Rα alone failed to induce GD. Co-injection of two plasmids induced more severe GD + GO than pcDNA3.1/TSHR-289( +) alone.

[A randomized controlled trial on the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing in the treatment of deep partial-thickness burn wounds in children].

Objective: To explore the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing (hereinafter referred to as foam dressing) in treating the deep partial-thickness burn wounds in children. Methods: This study was a randomized controlled trial. From June 2021 to December 2022, 78 pediatric patients with deep partial-thickness burns who met the inclusion criteria were admitted to the Department of Burns in Guiyang Steel Plant Employees Hospital. According to the random number table, the pediatric patients were divided into two groups, with 38 cases left in combined treatment group (with 20 males and 18 females, aged 26.00 (16.75, 39.75) months) and 39 cases in foam dressing group (with 21 males and 18 females, aged 19.00 (14.00, 31.00) months) after the exclusion of one dropped-out child in follow-up. The pediatric patients in combined treatment group underwent eschar dermabrasion of the wound within 48 hours after injury, the wound was covered with foam dressing after operation, and the dressing was replaced once every 7 days; for the pediatric patients in foam dressing group, the wound was sterilized within 48 hours after injury and covered with foam dressing, and the dressing was replaced once every 2 to 3 days. After the wound healing, the children in both groups were routinely applied with silicone gel twice a day for 3 weeks before started wearing elastic sleeves for more than 18 hours a day, and continuously for over than 6 months. The degree of pain during dressing change was evaluated using the children's pain behavior inventory FLACC. The adverse reactions during the treatment period, number of dressing changes, and wound healing time were observed and recorded. Six months after wound healing, the Vancouver scar scale (VSS) was used to evaluate the condition of the wound scar. Results: When changing dressing, the FLACC score for pain of pediatric patients in combined treatment group was 3.5 (2.0, 5.0), which was significantly lower than 6.0 (5.0, 8.0) in foam dressing group (Z=-5.40, P<0.05). During the treatment period, no adverse reactions such as wound edema, fluid accumulation, or peripheral skin rash allergies occurred in any pediatric patient in both groups. The number of dressing changes of pediatric patients in combined treatment group was 3 (3, 4) times, which was significantly less than 8 (7, 10) times in foam dressing group (Z=-7.58, P<0.05). The wound healing time of pediatric patients in combined treatment group was (19±5) days, which was significantly shorter than (25±6) days in foam dressing group (t=-4.48, P<0.05). Six months after wound healing, the VSS score for scar of pediatric patients in combined treatment group was 5 (2, 8), which was significantly lower than 7 (5, 10) in foam dressing group (Z=-3.05, P<0.05). Conclusions: Compared with using foam dressings alone, early eschar dermabrasion combined with foam dressings can reduce the number of dressing changes, alleviate the pain during dressing changes, and shorten the wound healing time in treating children with deep partial-thickness burns, and effectively alleviate scar hyperplasia by combining with anti-scar treatment post burns.

Cortico-cortical connectivity is influenced by levodopa in tremor-dominant Parkinson's disease.

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor.

[Retrospective analysis of 350 cases with dissection of lymph nodes posterior to right recurrent laryngeal nerve in endoscopic thyroidectomy through gasless axillary posterior approach].

Objective: To evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach. Methods: A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data. Results: All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%). Conclusion: The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients.

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

[Pay attention to burn rehabilitation assessment].

With the vigorous development of burn rehabilitation, many burn units in China are paying more and more attention to the application of burn rehabilitation treatment methods in burn patients. However, the development of burn rehabilitation assessment cannot be ignored in the process of burn rehabilitation treatment. Burn rehabilitation assessment is characterized with a long assessment time span and a large and complex assessment contents, resulting in the inability to develop a standardized assessment form that is suitable for all burn patients. In addition, factors including the shortage of professionals in burn rehabilitation assessment in some domestic burn units, relatively small number of objective assessment instruments and various institutional limitations, have also led to insufficient motivation and low quality of burn rehabilitation assessment. Based on those, this article analyzes the characteristics and main contents of burn rehabilitation assessment in China, and puts forward some suggestions in view of the shortcomings of burn rehabilitation assessment, in order to provide a reference for burn rehabilitation practitioners.

Identification and functional analysis of circRIPK2 in lipopolysaccharide induced chicken macrophages.

1. It was hypothesised that a circular RIPK2 (circRIPK2) highly expressed in chicken macrophages plays an important role during bacterial infection.2. After PCR amplification, Sanger sequencing and RNase R exonuclease treatment of chicken macrophages, it was found that circRIPK2 was a stable circular RNA, which was formed by reverse splicing of exons 4 to 9 of the RIPK2.3. The circRIPK2 can promote the lipopolysaccharide (LPS) induced cellular injury by reducing cell viability and increasing the expression of pro-inflammatory cytokines and apoptosis genes.4. Six miRNAs were identified as interacting with circRIPK2, potentially targeting 1,817 genes, which were significantly enriched in the Wnt signalling pathway, adherens junction and NOD-like receptor signalling pathway.5. This study provides better understanding of the function of circRIPK2, which may prove a potential biomarker and indicate potential targets for the treatment of bacterial infection.

Transtubular Transoral Approach for Irreducible Ventral Craniovertebral Junction Compressive Pathologies: Surgical Technique and Outcome.

Introduction: To investigate the use of a tubular retractor to provide access to the craniovertebral junction (CVJ) sparing the soft palate with the aim of reducing complications associated with traditional transoral approach but yet allowing adequate decompression of the CVJ. Materials and methods: Twelve consecutive patients with severe myelopathy (JOA-score less than 11) from ventral CVJ compression were operated between 2014-2020 using a tubular retractor assisted transoral decompression. Results: All patients improved neurologically statistically (p=0.02). There were no posterior pharynx wound infections or rhinolalia. There was one case with incomplete removal of the lateral wall of odontoid and one incidental durotomy. Conclusions: A Tubular retractor provides adequate access for decompression of the ventral compression of CVJ. As the tubular retractor pushed away the uvula, soft palate and pillars of the tonsils as it docked on the posterior pharyngeal wall, the traditional complications associated with traditional transoral procedures is completely avoided.

Social demographics determinants for resistome and microbiome variation of a multiethnic community in Southern Malaysia.

The prevalence of antibiotic-resistant bacteria in Southeast Asia is a significant concern, yet there is limited research on the gut resistome and its correlation with lifestyle and environmental factors in the region. This study aimed to profile the gut resistome of 200 individuals in Malaysia using shotgun metagenomic sequencing and investigate its association with questionnaire data comprising demographic and lifestyle variables. A total of 1038 antibiotic resistance genes from 26 classes were detected with a mean carriage rate of 1.74 ± 1.18 gene copies per cell per person. Correlation analysis identified 14 environmental factors, including hygiene habits, health parameters, and intestinal colonization, that were significantly associated with the resistome (adjusted multivariate PERMANOVA, p < 0.05). Notably, individuals with positive yeast cultures exhibited a reduced copy number of 15 antibiotic resistance genes. Network analysis highlighted Escherichia coli as a major resistome network hub, with a positive correlation to 36 antibiotic-resistance genes. Our findings suggest that E. coli may play a pivotal role in shaping the resistome dynamics in Segamat, Malaysia, and its abundance is strongly associated with the community's health and lifestyle habits. Furthermore, the presence of yeast appears to be associated with the suppression of antibiotic-resistance genes.

Readability and quality of online patient health information on parotidectomy.

OBJECTIVE: Complications of parotidectomy can have a massive impact on patients' quality of life. This study aimed to evaluate the readability and quality of online health information on parotidectomy. METHOD: The search terms 'parotidectomy', 'parotid surgery', 'parotidectomy patient information' and 'parotid surgery patient information' were parsed through three popular search engines. RESULTS: The websites were analysed using readability scores of the Flesch Reading Ease test and the Gunning Fog Index. The DISCERN instrument was used to assess quality and reliability. The average Flesch Reading Ease score was 50.2 ± 9.0, indicating that the materials were fairly difficult to read, the Gunning Fog Index score showed that the patient health information was suitable for an individual above 12th grade level, and the DISCERN score indicated that the online patient health information had fair quality. The Kruskal-Wallis test showed a significant difference in Flesch Reading Ease and DISCERN tool scores according to website category (p < 0.05). CONCLUSION: Current online patient health information on parotidectomy is too difficult for the public to understand, and it exceeds the reading levels recommended by Health Education England and the American Medical Association.

A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts.

SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.

[Progress on development and application of the diet-related inflammatory index in cancer epidemiological studies].

Cancer is a major public health problem worldwide, causing an more serious burden of disease. Inflammation is considered a predisposing factor for cancer with close relationship with its incidence. In recent years, the public and epidemiologists has paid more attention to the association between nutrition and cancer and other chronic diseases in the perspective of inflammation. This paper summarizes the development and application of the diet-related inflammatory index in cancer epidemiological studies based on the literature retrieval of common diet-related inflammatory index. Firstly, we highlight the common diet-related inflammatory indices and their construction methods, such as the Dietary Inflammatory Index, a literature-derived diet-related inflammatory index, and the Empirical Dietary Inflammatory Index, an empirically derived diet-related inflammatory index, and so on. Secondly, the epidemiological research progress on the commonly used diet-related inflammatory indices is briefly introduced. Finally, the advantages and disadvantages of the two types of this inflammatory indices are also briefly described for the purpose of providing reference for nutrition epidemiological studies of cancer and other chronic diseases in China.

Retraction Note: Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal.

The article "Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal", by K. Zhao, J.-Y. Tan, Q.-D. Mao, K.-Y. Ren, B.-G. He, C.-P. Zhang, L.-Z. Wei published in Eur Rev Med Pharmacol Sci 2019; 23 (1): 312-320-DOI: 10.26355/eurrev_201901_16778-PMID: 30657572 has been retracted by the authors for the following reasons: We are still conducting research in the effect of long non-codingRNA TUG1 in interstitial cells of Cajal recently. It turned out that some of the current experimental results are inconsistent with the previous results. Some data cannot be repeated by further research. We need to further confirm the effect of long non-coding RNA TUG1 on alleviating TNF-α-induced inflammatory injury in interstitial cells of Cajal and for this reason, the authors all agreed to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16778.

The effect of medical education and counselling on treatment adherence and disease severity in patients with acne vulgaris: a non-randomised interventional study.

INTRODUCTION: Acne vulgaris (AV) is a common inflammatory skin disease affecting adolescents and young adults. It affects one's self-esteem and social relationship. In addition, poor adherence to treatment can cause poor treatment response and disease recurrence. This study aims to determine the effectiveness of medical education and counselling on treatment adherence and disease severity. METHODS: This is a non-randomised interventional study with age- and treatment- matched control conducted in a tertiary dermatology clinic from July 2021 to June 2022. Patients in the intervention group received a 10 min video presentation on acne, followed by treatment counselling. The adherence rate was determined objectively (pill counting and tube weighing) and subjectively (ECOB questionnaire). The disease severity was assessed using the Comprehensive Acne Severity Scale (CASS) and Global Acne Grading System (GAGS). RESULTS: A total of 100 patients completed the 12-week study. With intervention, patients have better adherence to topical medication (5% benzoyl peroxide gel: 71% vs 57.9%, p= 0.031; 0.05% tretinoin cream: 58.7% vs 45.4%, p= 0.044) at week 12. However, the intervention program did not improve adherence to oral medication. Overall, with intervention, a significantly higher percentage of improvement in disease severity was noted (47.3% vs. 39.1%, p=0.044). Nonadherence to treatment was attributed mostly to forgetfulness in 54% of the patients, followed by a busy lifestyle (41%) and little knowledge of acne (26%). CONCLUSION: Patients have significantly better adherence to topical medication with education and counselling. Better adherence to treatment leads to more remarkable disease improvement.

Plasmodium knowlesi circumsporozoite protein: genetic characterisation and predicted antigenicity of the central repeat region.

Circumsporozoite protein (CSP) central repeat region is one of the main target regions of the RTS,S/AS01 vaccine for falciparum infection as it consists of immunodominant B cell epitopes. However, there is a lack of study for P. knowlesi CSP central repeat region. This study aims to characterise the CSP repeat motifs of P. knowlesi isolates in Peninsular Malaysia. CSP repeat motifs of 64 P. knowlesi isolates were identified using Rapid Automatic Detection and Alignment of Repeats (RADAR). Antigenicity of the repeat motifs and linear B cell epitopes were predicted using VaxiJen 2.0, BepiPred-2.0 and BCPred, respectively. A total of 35 dominant repeat motifs were identified. The repeat motif "AGQPQAQGDGANAGQPQAQGDGAN" has the highest repeat frequency (n=15) and antigenicity index of 1.7986. All the repeat regions were predicted as B cell epitopes. In silico approaches revealed that all repeat motifs were antigenic and consisted of B cell epitopes which could be designed as knowlesi malaria vaccine.