Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

This article reports the case of an adolescent patient presenting with recurrent epistaxis and orthostatic hypoxemia. Chest imaging revealed multiple bilateral pulmonary nodules of varying sizes and mixed densities. The presence of intrapulmonary right-to-left shunting was confirmed through bubble contrast echocardiography, pulmonary first-pass perfusion imaging, and the pure oxygen inhalation formula method. Whole-genome sequencing identified a mutation in the SMAD4 gene, and subsequent family analysis confirmed the diagnosis of hereditary hemorrhagic telangiectasia (HHT). Currently, there is no international consensus on the management of such rare presentations. Based on relevant case reports in the literature, the patient was empirically treated with a combination of amlodipine and thalidomide. After one year of follow-up, significant improvement in hypoxemia was observed. The diagnostic and therapeutic process of this case offers valuable insights for the clinical management of patients with mixed-type PAVMs caused by HHT.

Objective To study the effect of intra-aortic balloon pump(IABP)in the therapy of ST-segment-elevation myocardial infarction(STEMI)patients complicated with ventricular septal rupture(VSR).Methods A retrospective analysis was performed on 35 STEMI patients complicated with VSR.Those patients were admitted in Yan'an Hospital Affiliated to Kunming Medical University from January 2019 to June 2023.Patients were divided into the combine-treated group(20 cases)and the drug-treated group(15 cases)according to the therapeutic strategies.The combine-treated group received IABP implantation and drug therapy,and the drug-treated group only received drug therapy.The clinical characteristics,hemodynamic and cardiac function improvement and mortality were evaluated.Hemodynamic and cardiac function improvement were compared between the two groups.Results There were no statistically significant differences in age,male proportion and size of VSR between the two groups(P>0.05).In the combine-treated group,the average heart rate,the average arterial blood pressure,central venous pressure,the LVEF value of cardiac ultrasound,pleural effusion,B-Line of lung,the level of B-type natriuretic peptide(BNP),the level of serum creatinine and the level of serum lactic acid were improved at 72 h after IABP use(all P<0.05).All these indicators got worse in the drug-treated group.The mortality rate of the combine-treated group was markedly lower than that of the drug-treated group(P<0.05).The mortality rate of patients who received IABP implantation within 72 h after VSR was lower than that of patients who received IABP implantation beyond 72 h after VSR.Conclusion For patients with AMI complicated with VSR,implantation of IABP can significantly improve hemodynamics,cardiac function and reduce mortality.

Objective:To quickly identify the causes of morphological abnormalities of microcytic hypochromic erythrocytes that are detected during health checkups for recruitment of flying cadets, and to explore its role in medical selection.Methods:Students with hemoglobin (Hb)≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes detected during the 2023 medical selection of flying cadets by Guangzhou Selection Center were selected. Their medical history was collected, and iron metabolism, Hb electrophoresis and hemoglobin H (HbH) inclusion bodies were examined to screen for thalassemia and iron deficiency. The diagnosis of thalassemia was confirmed by thalassemia gene testing. Those with iron deficiency received iron supplementation therapy and the recovery of Hb was observed.Results:Ninety-one students were diagnosed with Hb≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes, accounting for 4.35% of the total. Among these cases, 85 with abnormal Hb electrophoresis and/or positive HbH inclusion body detection were confirmed as thalassemia minor via thalassemia genetic testing, and 3 cases with normal iron metabolism, Hb electrophoresis, and negative HbH inclusion body detection. A total of 88 cases of thalassemia minor were diagnosed, accounting for 96.70% of the total. Among them, 2 cases were complicated with iron deficiency while 3 were diagnosed with iron deficiency erythropoiesis. Out of the 91 students with Hb≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes, 9 were recruited, including 7 cases with thalassemia minor (Hb≥130 g/L), 1 case with thalassemia minor combined with iron deficiency erythropoiesis (Hb≥130 g/L after iron supplementation), and 1 case with iron deficiency erythropoiesis (Hb≥130 g/L after iron supplementation). Among the 9 recruits, 8 were followed up for over one year and the results of their military physical fitness tests all reached or exceeded the standards, but the remaining one dropped out and lost contact.Conclusions:Among physical examinees during medical selection of flying cadets in South China, thalassemia is the leading cause of morphological abnormalities of microcytic hypochromic erythrocytes. Results of iron metabolism, Hb electrophoresis, and HbH inclusion body detection can help identify thalassemia and iron deficiency quickly. Cases of morphological abnormalities of microcytic hypochromic erythrocytes caused by iron deficiency can be considered eligible for selection after Hb levels return to normal following iron supplementation therapy. Students who are diagnosed with thalassemia with Hb<130 g/L can be determined as ineligible. Such rapid identification can facilitate the medical selection of the above 2 types of students.

Objective To explore the mechanism of acupuncture protection of quadriceps muscle cells in knee osteoarthritis model rats based on Piezo1/YAP/Caspase3 axis.Methods 40 SPF grade Wistar rats were selected and adaptively fed for 7 days before being divided into three groups:sham surgery group,model group,western medicine group,and acupuncture group,with 10 rats in each group,according to a random control table.The model group,Western medicine group,and acupuncture group used the modified Hulth method to construct knee osteoarthritis models,while the sham surgery group only cut open the joint cavity and sutured it.After successful model replication,the sham surgery group was given physiological saline by gavage,the western medicine group was given celecoxib solution by gavage,and the acupuncture group was given acupuncture at the infrapatellar,crane top,and blood sea levels.Each group was intervened once a day for 14 consecutive days.During the treatment period,the rats continued to undergo treadmill training.After the intervention,the hematoxylin eosin staining method(HE)was used to detect the morphological changes of various rat quadriceps muscle tissues and articular cartilage;TUNEL method was used to detect apoptosis of quadriceps muscle cells,immunofluorescence method was used to detect the protein expression of Piezo1,YAP,and p-YAP in quadriceps muscle cells,Western blot method was used to detect the expression of anti apoptotic proteins CTGF,AREG,Gli2,AFP in quadriceps muscle tissue,as well as the protein expression levels of apoptosis related proteins Bcl-2,Bcl-xl,Bax,cytc,and Caspase3.Results Compared with the model group,the western medicine group and the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the western medicine group,the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the model group,the apoptosis index of the quadriceps muscle in the Western medicine group and acupuncture group rats was lower,and the apoptosis index of the quadriceps muscle in the acupuncture group was lower(P<0.05).Compared with the model group,the Western medicine group and acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps femoris muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Compared with the Western medicine group,the acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Conclusion Acupuncture increases the expression of Piezo1 protein in the quadriceps femoris muscle of knee osteoarthritis model rats,promotes the phosphorylation of YAP into the nucleus,thereby promoting proliferation,anti apoptotic proteins CTGF,AREG,Gli2,and AFP protein expression,inhibiting Caspase3-dependent mitochondrial apoptosis,and protecting muscle cells.

Objective To investigate the effects of meridian and tendon acupuncture on the mitochondrial apoptosis of quadriceps femoris muscle cells in model rats of knee osteoarthritis(KOA);To explore its mechanism for the treatment of KOA.Methods Totally 40 SPF healthy male Wistar rats were randomly divided into sham-operation group(10 rats)and modeling group(30 rats).The modified Hulth method was used to establish a KOA rat model.The model rats were randomly divided into model group,celecoxib group and meridian and tendon acupuncture group,with 9 rats in each group.Corresponding intervention measures were given to each group for 14 consecutive days.Improved Lequesne MG score was used for evaluating knee joint function in rats,measuring thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate and wet weight ratio of the affected limb,HE staining was used to observe the morphology of quadriceps femoris tissue,TUNEL method was used to detect apoptosis of quadriceps femoris cells,immunofluorescence was used to detect the expressions of reactive oxygen species(ROS),superoxide dismutase(SOD),Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue,fluorescence double staining method was used to detect the co-expression of ROS and Caspase-3 in quadriceps femoris tissue,Western blot was used to detect the expressions of apoptosis related proteins in quadriceps femoris tissue.Results Compared with the sham-operation group,the improved Lequesne MG score of the knee joint in the model group rats increased(P<0.05),the circumference of the thigh,wet weight of the quadriceps femoris,wet weight maintenance rate and wet weight ratio of the affected limb decreased(P<0.05),the arrangement of quadriceps femoris muscle fibers was disordered and loose,with some muscle fibers dissolved and necrotic,accompanied by a large amount of inflammatory exudate,an increase in lymphocytes,and an increase in cell apoptosis index(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue increased,while the expression of SOD decreased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,Cytochrome C(CytC),Caspase-3 and Caspase-9 in quadriceps femoris tissue increased(P<0.05).Compared with the model group,the improved Lequesne MG scores of the knee joint in the celecoxib group and the meridian and tendon acupuncture group decreased(P<0.05),while thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate,wet weight ratio increased(P<0.05),the structure of quadriceps femoris muscle fibers was normal,the muscle membrane was relatively intact,the apoptosis index decreased(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue decreased,while the expression of SOD increased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,CytC,Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue decreased(P<0.05),and the expression trend of ROS and Caspase-3 in fluorescent double staining was consistent.Conclusion Meridian and tendon acupuncture can reduce ROS in the quadriceps femoris tissue of KOA model rats,inhibit the expressions of mitochondrial apoptosis-related proteins,thereby improving skeletal muscle strength,and play a certain therapeutic role.

The number of patients with eye diseases in China is enormous,and the negative effects of these conditions,such as impaired visual function,psychological burdens,and restricted social participation,are becoming increasingly severe.Due to the limited and unevenly distributed ophthalmic resources,and the significant limitations of traditional diagnostic and therapeutic approaches in terms of accuracy and efficiency,there is an urgent need for more sensitive and efficient modalities.With the rapid advancement of artificial intelligence technology,ophthalmic diagnosis has entered a new stage of intelligent transformation.Facial photos,as a noninvasive and convenient medium,show unique advantages in eye disease diagnosis.Artificial intelligence systems based on facial photo analysis have been applied to the screening and diagnosis of conditions such as myopia,strabismus,ptosis,and thyroid eye disease,showing promising results.This review introduces the workflow of intelligent diagnosis for ocular diseases based on facial photographs,with a focus on recapitulating relevant research findings both domestically and internationally in recent years.It summarizes the innovative features and application advantages of intelligent diagnosis systems for eye diseases based on facial photos,analyzes the current technical bottlenecks and challenges in application,proposes corresponding countermeasures,and discusses future development directions,aiming to provide references and new insights for the intelligent screening and diagnosis of eye diseases.

Objective To investigate the prognostic significance of the neutrophil-to-platelet ratio(NPR)in combination with C-reactive protein(CRP)in patients with lower extremity arteriosclerosis obliterans(ASO).Methods A retrospective analysis was conducted on the clinical data of 209 patients with lower extremity ASO admitted to the Department of Critical Care Medicine at Zhongshan Hospital Affiliated to Fudan University(Xiamen)between January 2020 and February 2024.Patients were categorized into either the survival group or the death group based on their in-hospital prognosis.The NPR was calculated on the day of ICU admission,as was the level of CRP.Differences in NPR,CRP,and the combination of NPR and CRP between the two groups were then com-pared.The prognostic value of NPR,CRP,and their combined use for predicting outcomes in patients with lower extremity ASO was evaluated using receiver operating characteristic(ROC)curve analysis.Based on the optimal cutoff value derived from the ROC curve for the combination of NPR and CRP,patients were divided into two groups.Kaplan-Meier survival analysis was subsequently performed to assess differences in survival outcomes between these two groups.Results The levels of NPR,CRP,alanine aminotransferase,aspartate aminotransferase,creatinine,B-type natriuretic peptide,troponin,and procalcitonin,as well as the proportion of patients with kidney disease in the survival group,were significantly lower than those in the death group,and the differences were statistically significant(P<0.05).The albumin level in the survival group was significantly higher than that in the death group,with a statistically significant difference(P<0.05).Binary logistic regression analysis revealed that NPR,CRP,the combination of NPR and CRP,and the presence of comorbid kidney disease were independent risk factors influencing patient survival prognosis.ROC curve analysis showed that the areas under the curve(AUC)for NPR,CRP,and the combination of NPR and CRP were 0.648,0.812,and 0.828,respectively.Both CRP and the combination of NPR and CRP demonstrated statistically significant(P<0.05).Compared with either NPR or CRP alone,their combined use showed improved predictive performance.Based on the ROC curve for the combination of NPR and CRP,the optimal cutoff value was determined as 0.029 using the maximum Youden Index.Patients were then divided into high and low NPR+CRP groups according to this cutoff.Kaplan-Meier sur-vival analysis revealed that the in-hospital survival rate in the low NPR+CRP group was significantly higher than that in the high NPR+CRP group,and the difference in survival between the two groups was statistically significant(P=0.001).Conclusion NPR combined with CRP is associated with the prognosis of patients with lower extremity ASO and may serve as an effective predictive indicator for their clinical outcomes.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.