Safety and Efficacy of Upper Eyelid Orbicularis Oculi Botulinum Toxin in Patients with Synkinesis.

Background: Chemodenervation is an important means of treating oral-ocular synkinesis, but upper eyelid treatment is avoided due to risk of blepharoptosis. Objective: To measure the change in eyelid position among patients with oral-ocular synkinesis who received botulinum toxin to the upper eyelid orbicularis oculi compared with those who received lateral and lower eyelid treatment alone. Methods: In this retrospective clinical study, patients were categorized as having received lateral and lower eyelid botulinum toxin alone or having received upper eyelid botulinum toxin (to the preseptal and orbital orbicularis oculi) along with lateral and lower eyelid treatment. Pre- and posttreatment margin to reflex distance 1 (MRD1), margin to reflex distance 2 (MRD2), and palpebral height were measured using Emotrics software and compared using t tests and regression analysis. Results: Twenty-five patients were included. Mean age was 48.7 years and 24% were male. Mean duration of paralysis was 29 months (range 9-360 months). Posttreatment resting MRD1 (3.36) was not significantly different than pretreatment resting MRD1 (3.43) for patients who received upper eyelid botulinum toxin (p value = 0.60). Conclusion: Botulinum toxin to the upper eyelid orbicularis oculi injected superficially in small, concentrated aliquots did not result in blepharoptosis and was effective in reducing oral-ocular synkinesis.

Free flap reconstruction following head and neck trauma.

BACKGROUND: Free flap (FF) reconstruction of traumatic injuries to the head and neck is uncommon. METHODS: Multi-institutional retrospective case series of patients undergoing FF reconstruction for a traumatic injury (n = 103). RESULTS: Majority were gunshot wounds (GSW; 85%, n = 88) and motor vehicle accidents (11%, n = 11). Majority underwent osseous reconstruction (82%, n = 84). FF failures (9%, n = 9/103) occurred in GSW patients (100%, n = 9/9) and when multiple subsites were injured (89%, n = 8/9). Preoperative antibiotics correlated with lower rates of a neck washouts (4% vs. 19%) (p = 0.01) and 30-day readmissions (4% vs. 17%) (p = 0.02). CONCLUSIONS: All FF failures occurred in the setting of a GSW and the majority involved multiple subsites. Preoperative antibiotics correlated with lower rates of postoperative washout procedures and 30-day readmission.

[Analysis of genetic etiology of 234 deaths in the pediatric intensive care unit with suspected genetic diseases].

Objective: To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics. Methods: This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children's Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson's chi-square test or Fisher's exact probability method were used to compare the clinical characteristics between the groups. Results: A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions: Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.

[Primary observational study of tocilizumab in children with severe acute necrotizing encephalopathy].

Objective: To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE). Methods: It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann - Whitney U test or Chi-square test. Results: Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups (P=0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions: The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

[Prognostic factors of extracorporeal membrane oxygenation in the treatment of severe pediatric acute respiratory distress syndrome].

Objective: To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support. Methods: It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results: Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO2/FiO2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH2O (1 cmH2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis (P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO (P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO (P<0.05) and gradually increased from 24 h after ECMO. Conclusions: The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

Facial Nerve Pathology in Children.

Facial nerve pathology in children has devastating functional and psychosocial consequences. Facial palsy occurs less commonly in children than adults with a greater proportion caused by congenital causes. Most pediatric patients have normal life expectancy and few comorbidities and dynamic restoration of facial expression is prioritized. This article will focus on the unique aspects of care for facial palsy in the pediatric population.

Risk factors for multidrug-resistant and extensively drug-resistant Acinetobacter baumannii infection of patients admitted in intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii infections pose challenges for clinical treatment and cause high mortality, particularly in intensive care units (ICUs). AIM: To systematically summarize and analyse the risk factors for MDR/XDR A. baumannii-infected patients admitted to ICUs. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for eligible original studies published in English before October 2023. Meta-analysis was conducted where appropriate, with mean differences (MDs) and odds ratios (ORs) calculated for continuous and nominal scaled data. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). FINDINGS: Ten studies reporting 1199 ICU patients (604 from general ICUs, 435 from neonatal ICUs, and 160 from paediatric ICUs) from eight countries were included in our analysis. Risk factors associated with MDR A. baumannii infection among patients admitted to general ICUs included high Acute Physiology And Clinical Health II (APACHE Ⅱ) score (mean difference (MD): 7.52; 95% confidence interval (CI): 3.24-11.80; P = 0.0006), invasive procedures (odds ratio (OR): 3.47; 95% CI: 1.70-7.10; P = 0.0006), longer ICU stay (MD: 3.40; 95% CI: 2.94-3.86; P < 0.00001), and use of antibiotics (OR: 2.69; 95% CI: 1.22-5.94; P = 0.01). In the sub-group analysis, longer neonatal ICU stay (MD: 16.88; 95% CI: 9.79-23.97; P < 0.00001) was associated with XDR A. baumannii infection. CONCLUSION: Close attention should be paid to patients with longer ICU stays, undergoing invasive procedures, using antibiotics, and with high APACHE Ⅱ scores to reduce the risk of MDR and XDR A. baumannii infections.

Management of facial nerve trauma.

PURPOSE OF REVIEW: To present the current literature on management of facial nerve disorder secondary to trauma, with a focus on the utility of electrodiagnostic testing in this setting. RECENT FINDINGS: Patients with facial palsy related to temporal bone fractures should be started on high-dose corticosteroids as early as possible. Recent literature on the benefit of surgical intervention in the setting of temporal bone fracture is mixed. Some studies support early surgical decompression whereas others have found no benefit compared with conservative treatment. SUMMARY: The management of facial nerve trauma is based on location and extent of injury. Extratemporal trauma and transected nerve should be treated with surgical exploration and tension-free coaptation ideally within 72 h. There are no guidelines for intratemporal facial nerve trauma. Surgical decompression compared with medical management is debated in the literature without consensus and more large studies are needed.

[Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats].

OBJECTIVE: To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism. METHODS: SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release. RESULTS: Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl2-induced vascular contraction. CONCLUSION: Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow, thereby reducing systolic blood pressure in rats.

[Metagenomic next-generation sequencing-based retrospective investigation of the drug resistance sites of Mycoplasma pneumoniae in children].

Objective: To analyze the drug-resistant gene loci of Mycoplasma pneumoniae (MP) using metagenomic next-generation sequencing (mNGS). Methods: From November 2022 to October 2023, 697 clinical samples (including sputum, alveolar lavage fluid and blood) of 686 children with Mycoplasma pneumoniae positive detected by mNGS were retrospectively analyzed. Samples were divided into intensive care unit (ICU) group and non-ICU group, Chi-square test was used to compare groups, and Mann-Kendall trend test was used to analyze the change trend of the detection rate of drug resistance gene loci over time. Results: Of the 697 samples, 164 were from the ICU group and 533 were from the non-ICU group. The detection rate of Mycoplasma pneumoniae resistance gene was 44.3% (309/697), and all detected drug-resistant gene loci of MP were A2063G. The detection rate of Mycoplasma pneumoniae in ICU group was 50.0% (82/164), and the detection rates of Mycoplasma pneumoniae resistance gene loci in sputum, alveolus lavage fluid and blood samples were 75.0% (18/24) and 48.4% (62/128), respectively. The detection rate in sputum was higher than alveolus lavage fluid samples (χ2=5.72,P=0.017). The detection rate of Mycoplasma pneumoniae in non-ICU group was 42.6% (227/533), the detection rate of Mycoplasma pneumoniae resistance gene loci in sputum and alveolar lavage fluid was 40.0% (16/40), 44.3% (201/454), and no detection rate in blood samples (0/12). There was no significant difference in the detection rate of alveolar lavage fluid and sputum (χ2=0.27, P=0.602). From November 2022 to October 2023, the detection rate of submitted samples showed an increasing trend month by month (overall: Z=3.99, ICU inspection group: Z=2.93, non-ICU group: Z=3.01, all P<0.01). Among the bacteria commonly detected with Mycoplasma pneumoniae, Streptococcus pneumoniae accounted for the highest proportion, the detection rate was 15.5% (108/697), and Epstein-Barr virus accounted for the highest proportion of 17.6% (123/697). Conclusions: From November 2022 to October 2023, the detection rate of Mycoplasma pneumoniae drug resistance gene loci showed an increasing trend. The detection rate of drug resistance gene loci in sputum samples of ICU group was higher than alveolus lavage fluid. No new drug resistance site were detected.

[Quantitative analysis of risk assessment indicators for re-introduction of imported malaria in China].

OBJECTIVE: To quantitatively analyze the risk indicators of re-introduction of imported malaria in China and their weighting coefficients, so as to investigate the difference in the contribution of risk indicators included in the current risk assessment framework for re-introduction of imported malaria in China to the risk assessment of re-introduction of imported malaria. METHODS: Publications pertaining to the risk assessment framework for re-introduction of imported malaria in China that reported the risk indicators and their weighting coefficients were retrieved in PubMed, Web of Science, CNKI, Wanfang Data, and VIP with terms of "malaria", "re-introduction/re-transmission/re-establishment", "risk assessment/risk evaluation/risk prediction" from the inception of the database through 3 August 2023, and literature search was performed in Google Scholar to ensure the comprehensiveness of the retrieval. Basic characteristics of included studies were extracted using pre-designed information extraction forms by two investigators, and data pertaining to risk indicators of re-introduction of imported malaria were cross-checked by these two investigators. The risk indicators included in the risk assessment framework for re-introduction of imported malaria in China and their weighting coefficients were visualized with the Nightingale's rose diagrams using the software R 4.2.1, and the importance of risk indictors was evaluated with the frequency of risk indicators included in the risk assessment framework and the ranking of weighting coefficients of risk indicators. In addition, the capability of risk indicators screened by different weighting methods was compared by calculating the ratio of the maximum to the minimum of the weighting coefficients of the risk indicators screened by different weighting methods. RESULTS: A total of 2 138 publications were retrieved, and following removal of duplications and screening, a total of 8 publications were included in the final analysis. In these 8 studies, 8 risk assessment frameworks for re-introduction of imported malaria in China and 52 risk indicators of re-introduction of imported malaria were reported, in which number of imported malaria cases (n = 8) and species of malaria vectors were more frequently included in the risk assessment frameworks (n = 8), followed by species of imported malaria parasites (n = 6) and population density of local malaria vectors (n = 6), and species of local malaria vectors (n = 6), number of imported malaria cases (n = 5) and species of imported malaria parasites had the three highest weighting coefficients (n = 4). The weighting methods included expert scoring method, combination of expert scoring method and analytic hierarchy process, and combination of expert scoring method and entropy weight method in these 8 studies, and the ratios of the maximum to the minimum of the weighting coefficients of the risk indicators screened by the expert scoring method were 1.143 to 2.241, while the ratios of the maximum to the minimum of the weighting coefficients of the risk indicators screened by combination of the expert scoring method and analytic hierarchy process were 34.970 to 162.000. CONCLUSIONS: Number of imported malaria cases, species of imported malaria parasites, species of local malaria vectors and population density of local malaria vectors are core indicators in the current risk assessment framework for re-introduction of imported malaria in China. Combination of the expert scoring method and analytic hierarchy process is superior to the expert scoring method alone for weighting the risk indicators.

Identification of new subtypes and potential genetic signatures in triple-negative breast cancer using weighted gene co-expression network analysis.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Here, we used gene expression profiling to define new subtypes of TNBC, which may improve prevention and treatment through personalized medicine. MATERIALS AND METHODS: Gene expression profiles from the public datasets GSE76250, GSE61724, GSE61723, and GES76275 were subjected to co-expression analysis to identify differentially expressed genes (DEGs) between TNBC and non-TNBC tissues. Consistency clustering was used to define TNBC subtypes, whose correlation with gene modules was analyzed. Enrichment analysis was used to identify module genes' biological functions and pathways. Single-sample gene set enrichment analysis was used to assess immune cell infiltration in the different TNBC subtypes, and the ChAMP package was used to examine methylation sites in TNBC. RESULTS: A total of 4,958 DEGs in TNBC were identified, which showed the same expression differences across all datasets as in the dataset GSE76250 and clustered into 9 co-expression modules. TNBC samples clustered into two subtypes based on nine hub genes from the modules. Class I showed the most significant correlation with module 1, whose genes were related mainly to interleukin-1 response, while class II showed the most significant correlation with module 6, whose genes were related mainly to the transforming growth factor-ß pathway. Class I was significantly enriched in cell cycle and DNA replication, and tumors of this subtype showed lower immune cell infiltration than class II tumors. Tumor infiltration by Th2 cells correlated positively with the expression of MCM10 and negatively with the expression of PREX2. A greater methylation of CIDEC, DLC1, EDNRB, EGR2 and SRPK1 correlated with better prognosis. CONCLUSIONS: Class I TNBC, for which a useful biomarker is MCM10, may be associated with a worse prognosis than class II TNBC, for which PREX2 may serve as a biomarker.

[Efficacy and safety of different nerve block methods for the treatment of pudendal neuralgia].

Objective: To identify efficacy and safety of pudendal nerve block in tubing through the third posterior sacral foramen for the treatment of pudendal neuralgia (PN). Methods: A retrospective study with 222 PN patients was conducted in the Department of Pain Management of Beijing Tsinghua Changgung Hospital from January 2020 to April 2023. These patients were divided into two groups based on their treatment methods: pudendal nerve block in tubing through the third posterior sacral foramen (observation group, n=101) and ultrasound-guided pudendal nerve block (control group, n=121). Primary outcome measure was the 90-day postoperative pain relief rate. Secondary outcome measures included visual analog scale (VAS) at 1, 7, 14, 30 and 90 d after surgery, the incidence of tramadol uses after surgery, postoperative self-rating anxiety scale (SAS) scores and the incidence of adverse events. Factors that influenced pain relief within 90 days after surgery were analyzed by using binary logistic regression analysis. Results: Observation group included 34 males and 67 females, aged (49.8±16.0) years old. Control group included 38 males and 83 females, aged (43.7±14.0) years old. The 90-day postoperative pain relief rate of the observation group patients was 38.6% (39/101), which was higher than the 24.0% (29/121) of the control group patients (P=0.018). Both the observation group and the control group showed an interaction effect of time and group after treatment for VAS scores (both P<0.05). In intra-group comparison, the VAS scores at 1, 7, 14, 30 and 90 d after treatment in both groups were lower than those before treatment (all P<0.05). In inter-group comparison, the differences of the VAS scores were not statistically significant in the observation group compared with those in the control group at 1, 7, 14, 30 and 90 d after surgery (all P>0.05). The SAS score of the observation group at 90 d after surgery was 51.5±6.2, which was lower than the 53.4±5.8 of the control group (P=0.022). There was no statistically significant difference in the incidence of postoperative tramadol uses and adverse events between the two groups (both P>0.05). Pudendal nerve block in tubing through the third posterior sacral foramen was a protective factor for pain postoperative relief in PN patients at 90 d after surgery (OR=1.92, 95%CI: 1.05-3.48, P=0.033). Conclusion: Pudendal nerve block in tubing through the third posterior sacral foramen is a safe and effective minimally invasive treatment. It has a higher postoperative pain relief rate within 90 d after surgery, without increasing the uses of postoperative rescue analgesics and the incidence of adverse events.

[High expression of CPNE3 correlates with poor long-term prognosis of gastric cancer by inhibiting cell apoptosis via activating PI3K/AKT signaling].

OBJECTIVE: To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer (GC) and the possible mechanism. METHODS: We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February, 2013 to October, 2017. TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients. GO analysis was performed to predict the biological role of CPNE3 in GC. We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown, CPNE3 overexpression and LY294002 (a PI3K/AKT inhibitor) treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting. RESULTS: TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC (P < 0.05). The patients with high CPNE3 expressions had a reduced 5-year survival (P < 0.01), and a high CPNE3 expression, CEA level≥5 µg/L, CA19-9 level ≥37 kU/L, T3-T4 stage, and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery. The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59% and 74.55%, respectively (P < 0.05). GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis. In MGC803 cells, CPNE3 knockdown significantly increased cell apoptosis, enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression, while CPNE3 overexpression produced the opposite results (P < 0.05). The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression (P < 0.05). Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells (P < 0.05). CONCLUSION: CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Commentary on: "Frontal Osteomyelitis and Sinusitis Complication After Type III Frontal Bone Cranioplasty for Facial Feminization" by Brown et al.

We present a complementary report of a 38-year-old XY intersex female with frontal mucopyocele developing 5 years after frontal setback for gender-affirming surgery to supplement recent report by Brown et al: Frontal Osteomyelitis and Sinusitis Complication After Type III Frontal Bone Cranioplasty for Facial Feminization by Brown et al.

[Comparison of diagnostic criteria for acute kidney injury in critically ill children].

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ2=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.

[Survey on the application of external cardiopulmonary resuscitation in Chinese children with sudden cardiac arrest].

Objectives: To investigate the current application status and implementation difficulties of extracorporeal cardiopulmonary resuscitation (ECPR) in children with sudden cardiac arrest. Methods: This cross-sectional survey was conducted in 35 hospitals. A Children's ECPR Information Questionnaire on the implementation status of ECPR technology (abbreviated as the questionnaire) was designed, to collect the data of 385 children treated with ECPR in the 35 hospitals. The survey extracted the information about development of ECPR, the maintenance of extracorporeal membrane oxygenation (ECMO) machine, the indication of ECPR, and the difficulties of implementation in China. These ECPR patients were grouped based on their age, the hospital location and level, to compare the survival rates after weaning and discharge. The statistical analysis used Chi-square test and one-way analysis of variance for the comparison between the groups, LSD method for post hoc testing, and Bonferroni method for pairwise comparison. Results: Of the 385 ECPR cases, 224 were males and 161 females. There were 185 (48.1%) survival cases after weaning and 157 (40.8%) after discharge. There were 324 children (84.2%) receiving ECPR for cardiac disease and 27 children (7.0%) for respiratory failure. The primary cause of death in ECPR patients was circulatory failure (82 cases, 35.9%), followed by brain failure (80 cases, 35.0%). The most common place of ECPR was intensive care unit (ICU) (278 cases, 72.2%); ECPR catheters were mostly inserted through incision (327 cases, 84.9%). There were 32 hospitals (91.4%) had established ECMO emergency teams, holding 125 ECMO machines in total. ECMO machines mainly located in ICU (89 pieces, 71.2%), and the majority of hospitals (32 units, 91.4%) did not have pre-charged loops. There were no statistically significant differences in the post-withdrawal and post-discharge survival rates of ECPR patients among different age groups, regions, and hospitals (all P>0.05). The top 5 difficulties in implementing ECPR in non-ICU environments were lack of ECMO machines (16 times), difficulty in placing CPR pipes (15 times), long time intervals between CPR and ECMO transfer (13 times), lack of conventional backup ECMO loops (10 times), and inability of ECMO emergency teams to quickly arrive at the site (5 times). Conclusion: ECPR has been gradually developed in the field of pediatric critical care in China, and needs to be further standardized. ECPR in non-ICU environment remains a challenge.

Total lower lip reconstruction: a review of recent advances.

PURPOSE OF REVIEW: This review describes the fundamental principles and recent advances in the reconstruction of total lower lip defects to restore peri-oral aesthetic and function. RECENT FINDINGS: Modifications to the Abbe flap and visor flap have recently been described. Recent advances to free flap techniques have focused on dynamic restoration of lower lip sling function after reconstruction. This involves the transfer of innervated or noninnervated muscle tissue to reconstruct the lower lip to restore the sphincter function of the lips. SUMMARY: The reconstructive goals for a full thickness lower lip defect are to restore a functional oral sphincter, replace mucosal and external skin, and maintain a functional size of the oral aperture. Local flap reconstruction of sub-total lower lip defects is possible, but use of local flaps for total lip reconstruction often leads to microstomia. Several static and dynamic free tissue transfer options exist for lower lip reconstruction and have been summarized in this review.

[Quercetin improves pulmonary arterial hypertension in rats by regulating the HMGB1/RAGE/NF-κB pathway].

OBJECTIVE: To explore the mechanism through which quercetin improves pulmonary arterial hypertension (PAH). METHODS: Rat models of hypoxic pulmonary hypertension were established by exposure to hypoxia for 8-10 h each day (6 days a week for 4 weeks), and before each hypoxic exposure, the rats were given intragastric administration of 100 mg/kg quercetin or saline. After the treatments, the right ventricular systolic pressure (RVSP) and pulmonary artery systolic pressure of the rats were recorded. The right ventricular hypertrophy index (RVHI) was measured to evaluate right ventricular hypertrophy. HE staining was used to observe the remodeling of the pulmonary arterioles. The right cardiac function of the rats was evaluated by ultrasound. The protein levels of HMGB1, RAGE, NF-κB, Bax, Bcl-2 and cleaved caspase-3 in the lung tissue of the rats were detected using Western blotting. RESULTS: Compared with the rats maintained in normoxia, the rats with chronic hypoxic exposure showed significantly increased RVHI and RVSP (P<0.01), which were obviously lowered by quercetin treatment (P<0.01). HE staining showed significant pulmonary artery wall thickening with reduced lumen diameter in hypoxia group, and quercetin treatment effectively improved pulmonary vascular remodeling. Ultrasound examination revealed a significantly increased RVFW and a lowered PAT/PET ratio in hypoxia group (P<0.01), and such changes were ameliorated by quercetin treatment (P<0.01). Chronic hypoxia significantly increased the protein expressions of HMGB1 (P<0.01), RAGE, NF-κB and Bcl-2 (P<0.01) and lowered the protein expressions of Bax and cleaved caspase-3 (P<0.01); Quercetin treatment obviously lowered the protein expressions of HMGB1, NF-κB (P<0.05), RAGE (P<0.01) and (P<0.05) and increased the expressions of Bax and cleaved caspase-3 in the rat models (P<0.01). CONCLUSION: Quercetin improves pulmonary hypertension in rats possibly by promoting apoptosis through the HMGB1/RAGE/NF-κB pathway.