Objective:To summarize the clinical characteristics of children with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) caused by c.489G>A (p.Pro163=) compound heterozygous variants in the ECHS1 gene, and to explore genotype-phenotype correlations.Methods:A case series study was performed to analyze clinical, biochemical, metabolic, imaging, genetic, treatment and follow-up outcomes of 24 children with ECHS1 gene c.489G>A(p.Pro163=) variant, who were diagnosed in the Department of Neurology, Beijing Children′s Hospital from July 2010 to June 2024. Disease severity was assessed using the Newcastle Paediatric Mitochondrial Disease Scale, and Fisher exact test was applied to compare the improvement rate between valine-restricted and non-restricted groups.Results:These 24 children were all diagnosed after 2022, with a disease duration of 3.35 (1.25, 6.52) years at diagnosis. A total of 8 children initially had negative genetic results, and were finally confirmed by abnormal splicing of ECHS1 gene via skin fibroblast RNA sequencing, with the longest diagnostic time of 14 years. All 24 children presented with Leigh syndrome, including 11 boys and 13 girls, with an onset age of 1.46 (0.96, 2.79) years; 16 children (67%) were mild cases. Common initial symptoms included developmental delay (9 cases) and paroxysmal dystonia (9 cases), followed by developmental regression (3 cases), nystagmus (2 cases), and epilepsy (1 case). Main manifestations were dystonia (18 cases), developmental regression (14 cases), nystagmus (12 cases), developmental delay (11 cases), ataxia (10 cases), vision loss (9 cases), seizures (2 cases), and hearing impairment (1 case). Among 22 children who underwent blood and urine metabolic screening, 21 children (95%) had elevated urinary 2, 3-dihydroxy-2-methylbutyric acid and 19 children (86%) had elevated urinary S-(2-hydroxypropyl) cysteamine. All 24 children had symmetric abnormal signals in bilateral globus pallidus on cranial magnetic resonance imaging, 10 children had isolated globus pallidus involvement, and other common involved sites included caudate nucleus and brainstem (9 cases each), putamen (7 cases), and cerebral white matter (5 cases). At last follow-up, all 24 children survived, with a follow-up duration of 5.40 (2.75, 8.02) years and a maximum age of 17.8 years; 17 children (71%) had varying degrees of clinical improvement. There was no statistical difference in the improvement rate between children with or without valine-restricted diet (12/14 vs. 5/8, P=0.309). A total of 18 pathogenic variants in the ECHS1 gene were identified among 24 children, 13 of which were distributed in exons 7 and 8; those carrying c.308T>C, c.523G>A, c.796A>G, and c.832G>A variants were mostly severe cases. Conclusions:Children carrying ECHS1 gene c.489G>A(p.Pro163=) compound heterozygous variants face significant diagnostic delay. Clinical awareness of this synonymous variant needs further improvement for timely diagnosis. All these cases present as Leigh syndrome, mostly mild, with no clear genotype-phenotype correlation identified.

Objective:This study evaluated the accuracy of internal mammary sentinel lymph node biopsy(IM-SLNB)in patients with early-st-age breast cancer after receiving neoadjuvant therapy(NAT).It explored the benefits of IM-SLNB in guiding cancer staging,evaluating progn-osis,and optimizing adjuvant treatment strategies.Methods:A retrospective study was conducted to collect clinical data of patients who re-ceived IM-SLNB following NAT in Shandong Cancer Hospital and Institute from October 2013 to November 2023.We analyzed the influence of clinicopathological characteristics on internal mammary lymph node(IMLN)metastasis and assessed the prognostic significance of IMLN me-tastasis following NAT.Results:The study included 132 breast cancer patients who underwent IM-SLNB following NAT.The metastasis rates of axillary lymph nodes(ALN)and internal mammary lymph nodes(IMLN)were 90.9%(120/132)and 9.1%(12/132),respectively.The perce-ntages of patients in the following groups were as follows:ALN-positive/IMLN-positive(8.3%,11/132),ALN-positive/IMLN-negative(43.1%,57/132),ALN-negative/IMLN-positive(0.7%,1/132),and ALN-negative/IMLN-negative(47.7%,63/132).The detection rate of internal mam-mary sentinel lymph nodes(IM-SLN)after NAT was 98.5%(132/134);two patients could not undergo IM-SLNB owing to surgical difficulties.Among the 12 cases of IMLN metastasis,6 patients experienced a change in postoperative pathological staging:2 shifted from stage ⅢA toⅢC,2 from stage ⅡB to ⅢC,1 from stage ⅡA to ⅢA,and 1 from stage ⅡA to ⅢC.IMLN metastasis was determined to be an independ-ent risk factor for disease-free survival(DFS)and overall survival(OS)(P<0.05).Patients with IMLN metastasis demonstrated significantly lower DFS and OS than those without IMLN metastasis(P<0.05).Conclusions:The pathological status of both ALN and IMLN should be con-sidered in the axillary pathological response after NAT.Patients with detectable IMLN during surgery after NAT should undergo IM-SLNB to ensure comprehensive lymph node staging.The status of IMLN metastasis following NAT serves as an independent prognostic factor.

Objective:This study evaluated the accuracy of internal mammary sentinel lymph node biopsy(IM-SLNB)in patients with early-st-age breast cancer after receiving neoadjuvant therapy(NAT).It explored the benefits of IM-SLNB in guiding cancer staging,evaluating progn-osis,and optimizing adjuvant treatment strategies.Methods:A retrospective study was conducted to collect clinical data of patients who re-ceived IM-SLNB following NAT in Shandong Cancer Hospital and Institute from October 2013 to November 2023.We analyzed the influence of clinicopathological characteristics on internal mammary lymph node(IMLN)metastasis and assessed the prognostic significance of IMLN me-tastasis following NAT.Results:The study included 132 breast cancer patients who underwent IM-SLNB following NAT.The metastasis rates of axillary lymph nodes(ALN)and internal mammary lymph nodes(IMLN)were 90.9%(120/132)and 9.1%(12/132),respectively.The perce-ntages of patients in the following groups were as follows:ALN-positive/IMLN-positive(8.3%,11/132),ALN-positive/IMLN-negative(43.1%,57/132),ALN-negative/IMLN-positive(0.7%,1/132),and ALN-negative/IMLN-negative(47.7%,63/132).The detection rate of internal mam-mary sentinel lymph nodes(IM-SLN)after NAT was 98.5%(132/134);two patients could not undergo IM-SLNB owing to surgical difficulties.Among the 12 cases of IMLN metastasis,6 patients experienced a change in postoperative pathological staging:2 shifted from stage ⅢA toⅢC,2 from stage ⅡB to ⅢC,1 from stage ⅡA to ⅢA,and 1 from stage ⅡA to ⅢC.IMLN metastasis was determined to be an independ-ent risk factor for disease-free survival(DFS)and overall survival(OS)(P<0.05).Patients with IMLN metastasis demonstrated significantly lower DFS and OS than those without IMLN metastasis(P<0.05).Conclusions:The pathological status of both ALN and IMLN should be con-sidered in the axillary pathological response after NAT.Patients with detectable IMLN during surgery after NAT should undergo IM-SLNB to ensure comprehensive lymph node staging.The status of IMLN metastasis following NAT serves as an independent prognostic factor.

Objective:To summarize the clinical characteristics of children with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) caused by c.489G>A (p.Pro163=) compound heterozygous variants in the ECHS1 gene, and to explore genotype-phenotype correlations.Methods:A case series study was performed to analyze clinical, biochemical, metabolic, imaging, genetic, treatment and follow-up outcomes of 24 children with ECHS1 gene c.489G>A(p.Pro163=) variant, who were diagnosed in the Department of Neurology, Beijing Children′s Hospital from July 2010 to June 2024. Disease severity was assessed using the Newcastle Paediatric Mitochondrial Disease Scale, and Fisher exact test was applied to compare the improvement rate between valine-restricted and non-restricted groups.Results:These 24 children were all diagnosed after 2022, with a disease duration of 3.35 (1.25, 6.52) years at diagnosis. A total of 8 children initially had negative genetic results, and were finally confirmed by abnormal splicing of ECHS1 gene via skin fibroblast RNA sequencing, with the longest diagnostic time of 14 years. All 24 children presented with Leigh syndrome, including 11 boys and 13 girls, with an onset age of 1.46 (0.96, 2.79) years; 16 children (67%) were mild cases. Common initial symptoms included developmental delay (9 cases) and paroxysmal dystonia (9 cases), followed by developmental regression (3 cases), nystagmus (2 cases), and epilepsy (1 case). Main manifestations were dystonia (18 cases), developmental regression (14 cases), nystagmus (12 cases), developmental delay (11 cases), ataxia (10 cases), vision loss (9 cases), seizures (2 cases), and hearing impairment (1 case). Among 22 children who underwent blood and urine metabolic screening, 21 children (95%) had elevated urinary 2, 3-dihydroxy-2-methylbutyric acid and 19 children (86%) had elevated urinary S-(2-hydroxypropyl) cysteamine. All 24 children had symmetric abnormal signals in bilateral globus pallidus on cranial magnetic resonance imaging, 10 children had isolated globus pallidus involvement, and other common involved sites included caudate nucleus and brainstem (9 cases each), putamen (7 cases), and cerebral white matter (5 cases). At last follow-up, all 24 children survived, with a follow-up duration of 5.40 (2.75, 8.02) years and a maximum age of 17.8 years; 17 children (71%) had varying degrees of clinical improvement. There was no statistical difference in the improvement rate between children with or without valine-restricted diet (12/14 vs. 5/8, P=0.309). A total of 18 pathogenic variants in the ECHS1 gene were identified among 24 children, 13 of which were distributed in exons 7 and 8; those carrying c.308T>C, c.523G>A, c.796A>G, and c.832G>A variants were mostly severe cases. Conclusions:Children carrying ECHS1 gene c.489G>A(p.Pro163=) compound heterozygous variants face significant diagnostic delay. Clinical awareness of this synonymous variant needs further improvement for timely diagnosis. All these cases present as Leigh syndrome, mostly mild, with no clear genotype-phenotype correlation identified.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

Acid-sensing ion channels(ASICs) are a novel class of ligand-gated cation channels activated by extracellular acidification and belong to the epithelial sodium channels(DEG/ENaC) superfamily.Their biological functions have recently been found not only in the central nervous system but also relevant to the physiology and pathology of non-neuronal tissues such as taste buds, cardiovascular system and bones.This review concerns the latest research on the expression and functions of ASICs in non-neuronal tissues so as to promote the understanding of their physiological and pathological functions.

Seeing that the manual method to restore tooth has the disadvantages such as long "lead-time", assurance of quality highly depending on operator's technology, and real-time cure difficulty met by lots of dental patients coming up for tooth restoration, we put forward an algorithm of tool-path generation based on STL data model for roughing dental restoration. The algorithm can reconfigure the STL data of dental crown restoration quickly, can generates the multi-level offset wire-loop by the use of horizontal plane cutting triangle facets; and then on the basis of offset wire-loop, it can plan Zigzag and follow the contour machining tool path. The algorithm has been applied to Dental CAM software, through simulation machining, the result shows that it can not only generate interference-free tool path, but also save a lot of "lead-time" for dental restoration. Accordingly, the algorithm is of great value for reference in clinical application.
Algorithms ; Crowns ; Dental Restoration, Permanent ; methods ; Humans ; Software ; Therapy, Computer-Assisted ; methods

Objective To study the effects of methylene blue(MB), a soluble guanylate cyclase inhibitor , on intestinal perfusion and oxygenation in dogs with septic shock.Methods A septic shock model was established by lipopolysaccharide infusion.After resuscitation with normal saline infusion,2mg/kg MB was infused within 15min in seven dogs.Blood flow of the superior mesenteric artery (SMA) was measured respectively at baseline,post shock for 1h, after resuscitation and 30min after MB injection.Blood gas analysis was done , and oxygenation was calculated.Results Blood flow of the SMA was significantly decreased by 61 8%(P0 0 5 ) ,butO2 extrincreasedby 14 8% .Conclusions Septicshockindogsresultsinadecreaseinintestinalperfusionandanincreasein oxygenextraction ,whichcanbeimprovedbyMBinjection .Theintestinalperfusionispartlyincreasedbyvolumetherapy .