Objective:To explore the expression of filaggrin(FLG)in melanoma tissues and its correlation with clinicopathological features and prognosis in patients.Methods:A total of 70 melanoma patients treated at the People's Hospital Affiliated to Shandong First Medical University from June 2019 to August 2020 were selected as research subjects.Tumor tissues and adjacent tissues obtained during surgery were examined for FLG expression using immunohistochemistry.Based on FLG expression,patients were divided into a positive group and a negative group.The positive expression rates of FLG in tumor tissues,adjacent tissues and melanoma tissues with different pathological features were compared.The patients were followed up for 3 years,and based on prognosis,they were divided into a survival group(n=43)and a death group(n=27).The FLG positive expression rates were compared between the two groups.Kaplan-Meier survival curves were plotted,and survival times were compared.Results:The positive FLG expression rate in melanoma tissues was significantly lower than that in adjacent tissues(P<0.05).The proportions of patients with tumor diameter>1 cm,Breslow thickness>2 mm,local ulcer,TNM stage Ⅲ-Ⅳ,lymph node metastasis,and tumor invasion in positive FLG expression group were significantly lower than those in negative group(P<0.05 or P<0.01).Among the 70 patients,27 cases died and 43 survived,with a survival rate of 61.42%.The positive FLG expression rate was significantly lower in death group than that in survival group(P<0.05).The survival time of FLG-positive patients was significantly longer than that of FLG-negative patients(P=0.010).Multivariate Cox regression analysis revealed that Breslow thickness>2 mm,TNM grade Ⅲ-Ⅳ,lymph node metastasis,and tumor invasion were risk factors for the prognosis of melanoma patients(P<0.01 or P<0.001),while positive FLG expression was a protective factor(P<0.01 or P<0.001).Conclusion:FLG expression is significantly decreased in melanoma tissues and is associated with pathological features such as Breslow thickness,tumor stage,invasion,lymph node metastasis,and prognosis.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

Objective:To carry out clinical and genetic analysis for a child featuring Brain-Lung-Thyroid syndrome (BLTS).Methods:A child who had presented at the Children′s Hospital Affiliated to Shandong University on May 27, 2022 was selected as the study subject. Clinical data was collected. Trio-whole exome sequencing (Trio-WES) was carried out for the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The child was given individualized treatment following the diagnosis.Results:The child, a two-year-and-seven-month-old boy, had presented with global developmental delay, ataxia and hypothyroidism. WES revealed that he has harbored a heterozygous c. 674C>T variant of the NKX2-1 gene, based on which he was diagnosed with BLTS. CT scan revealed interstitial and parenchymal inflammation in his lungs, which was reduced by budesonide aerosol inhalation. Conclusion:Discovery of the novel c. 674C>T variant has enriched the mutational spectrum of the NKX2-1 gene. Budesonide aerosol may be used to treat lung inflammation associated with BLTS.

OBJECTIVE: To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old. METHODS: A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa. RESULTS: A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%). CONCLUSIONS The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.
Humans ; Infant ; Child ; Prospective Studies ; Bacterial Infections ; C-Reactive Protein ; Hospitals ; Interleukin-6 ; Procalcitonin

OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fetal neurodegenerative disease characterized by the progressive loss of upper and lower motor neu-rons,leading to skeletal muscle atrophy,weakness,and paralysis.Oxidative stress plays a crucial role in ALS pathogenesis,including the familial forms of the disease arising from mutations in the gene coding for superox-ide dismutase(SOD1).Additionally,the abnormal accu-mulation of TAR DNA-binding protein of 43 ku(TDP-43)is a pathological feature present in almost all patients,even though the pathogenesis of ALS is unclear.Current-ly,there is no drug that can cure ALS/FTLD.Tetramethyl-pyrazine nitrone(TBN)is a derivative of tetramethylapyr-azine,derived from traditional Chinese medicine Ligusti-cum chuanxiong,which has been extensively proven to have therapeutic effects on various models of neurode-generative diseases.METHODS We investigated the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse models.In the SOD1G93A trans-genic mouse model,TBN was administered to mice via intraperitoneal or intragastric injection after the onset of motor deficits.We injected the TDP-43M337V virus into the striatum of mice unilaterally and bilaterally,and then administered TBN 30 mg·kg-1 intragastrically to observe changes in behavior and survival rate of mice.RESULTS TBN slowed the progression of motor neuron disease,as evidenced by improved motor performance,reduced spi-nal motor neuron loss and associated glial response,and decreased skeletal muscle fiber denervation and fibrosis.TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1.In the mice with unilateral injection of TDP-43M337V into the striatum,TBN improved motor deficits and cognitive impairment in the early stages of disease progression.In mice with bilateral injection of TDP-43M337V into the striatum,TBN not only improved motor function but also prolonged survival.Moreover,we demonstrate that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3β and AMPK/PGC-1α/Nrf2 signaling pathways.CONCLUSION TBN shows promise as an agent for the treatment of ALS/FTLD.TBN is currently undergoing clinical investigation for several indications,including a Phase Ⅱ trial for ALS.

OBJECTIVE: To validate the diagnosis of an infant with elevated urine 3-methylglutaconic acid (3-MGA) through sequencing of the CLPB gene. METHODS: Genomic DNA of the infant was sequenced by next generation sequencing (NGS), and candidate pathogenic variants were verified by Sanger sequencing and bioinformatics analysis. RESULTS: NGS has revealed that the infant has carried a c.1085G>A (p.Arg362Gln) and a c.1700A>C (p.Tyr567Ser) of the CLPB gene, which were respectively inherited from her parents. Among these, c.1085G>A (p.Arg362Gln) is a novel variant which was unreported previously, and based on the ACMG guidelines, it was predicted to be a possible pathogenic variant. CONCLUSION Compound heterozygous variants c.1085G>A (p.Arg362Gln) and c.1700A>C (p.Tyr567Ser) of the CLPB gene probably underlay the disease in this infant. Genetic testing has confirmed the diagnosis.

OBJECTIVE: To analyze the clinical and genetic characteristics of an infant girl featuring comprehensive developmental backwardness. METHODS: The patient was subjected to clinical examination, gas chromatography mass spectrometry and next-generation sequencing (NGS). RESULTS: The child was insensitive to sound, could not turn over, raise head, laugh or recognize his mother. Laboratory tests were all normal, but metabolic analysis suggested 3-methylglutaconic aciduria due to elevated 3-methylglutaconic acid and 3-methylglutaric acid. NGS has detected two compound heterozygous CLPB variants in the child, namely c.1085G>A and c.1700A>C, which were respectively inherited from her father and mother. Bioinformatic analysis predicted both variants to be pathogenic. The patient was diagnosed with 3-methylglutaconic aciduria type VII (MGCA7). CONCLUSION The MGCA7 in the child was probably caused by CLPB gene variants. NGS has provided a powerful diagnostic tool for this rare disorder.
Endopeptidase Clp ; genetics ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Metabolism, Inborn Errors ; genetics