Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (Dmd^Mu/+) mice were obtained after genotype identification. Male hemizygous Dmd^Mu/+(Dmd^Mu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in Dmd^Mu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (Dmd^Mu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of Dmd^Mu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, Dmd^Mu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old Dmd^Mu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old Dmd^Mu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old Dmd^Mu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old Dmd^Mu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.

OBJECTIVE Investigating the clinical characteristics,risk factors,treatment strategies and prognosis of head and neck extramedullary plasmacytoma(HNEMP).METHODS To analyze indicators affecting survival and prognosis,retrospective study was conducted on the clinical data of 38 newly diagnosed and untreated patients with HNEMP who were admitted to Beijing Tongren Hospital from September 2008 to January 2022.RESULTS Among 38 patients,5 cases(13.2%)displayed a manifestation as cranial-nasal-orbital communication,and 8 cases(21.1%)involved a tumor with diameter≥5 cm.There were 17 patients(44.7%)who underwent surgical resection along,13 patients(34.2%)who received postoperative radiotherapy,8 cases(21.1%)who accepted chemotherapy,and 5 cases(13.2%)who experienced combined radiochemotherapy.Following treatment evaluation,32 cases achieved CR,3 cases showed PR,1 case demonstrated SD and 2 cases experienced PD.The median follow-up time was 86 months,with 5-year PFS and OS rates of 92.1%and 94.7%,respectively.Of note,the patients with cranial-nasal-orbital communication exhibited significantly unfavorable 5-year PFS and OS rates of 40%and 60%,respectively,with median PFS of 13 months,whereas the patients in other groups achieved 100%of 5-year PFS and OS rates.Additionally,tumor diameter≥5 cm and the involvement of cranial-nasal-orbital communication were adverse prognostic factors for both PFS and OS.CONCLUSION HNEMP is a rare disease and the primary treatment approach is surgery combined with radiotherapy.The prognosis for HNEMP tends to be relatively favorable,with the involvement of cranial-nasal-orbital communication and high tumor burden as the adverse prognostic indicators.

Objective:To evaluate the safety and efficacy of enhanced recovery after surgery(ERAS) in the perioperative period of congenital choledochal cysts in children.Methods:This is a multicenter prospective randomized controlled study. The clinical data of 273 pediatric congenital choledochal cysts(CCC) patients who underwent surgery at 14 medical centers with complete follow-up data were collected through the medical data analysis platform. Among them, 123 cases in ERAS group were managed perioperatively in strict accordance with ERAS mode, and 150 cases in conventional group were managed according to traditional mode. The length of hospital stay,time to first farting, time to complete feeding, the incidence of complications, cost and readmission rate within 30 days,stress indexes and liver function were compared between the two groups.Results:Compared with the conventional group, median time to start farting (2.0 d vs. 3.0 d, P<0.001), median time to complete feeding (5.0 d vs. 7.0 d, P<0.001), median postoperative hospitalization time (6.0 d vs. 9.0 d, P<0.001),the median total length of stay(13.0 d vs. 15.0 d, P<0.001) were shorter,the median hospitalization cost (37,000 yuan vs.43,000 yuan P<0.001) was lower, and stress indexes recovered quickly. The incidence of postoperative hospital stay and readimission rate within 30 d were not statistically different between the two groups. Conclusion:It is safe and feasible to implement ERAS for children with CCC in the perioperative period, which can reduce stress response, speed up recovery,and save medical costs.

Objective To investigate the expression levels of scf and c-kit under the regulation of Dahuang Lingxian prescription and the possible mechanism of its effect on gallbladder dynamics, and to provide a theoretical basis for Dahuang Lingxian prescription in preventing the development and recurrence of cholesterol gallstone. Methods A total of 45 specific pathogen-free healthy male guinea pigs were randomly divided into normal group, model group, and traditional Chinese medicine (TCM) group. The guinea pigs in the normal group were fed with normal diet, and those in the model group and the TCM group were fed with high-fat lithogenic diet. After 8 weeks of feeding, 5 guinea pigs were randomly selected from each group, and successful modeling was determined if gallstone was observed with the naked eye in more than 4 guinea pigs. After successful modeling, the guinea pigs in the TCM group were given Dahuang Lingxian prescription by gavage, and those in the model group were given an equal volume of normal saline by gavage. After 8 consecutive weeks of administration by gavage, gallbladder tissue samples were collected, and HE staining was used to observe the pathological changes of gallbladder tissue; Western blot was used to measure the expression level of tumor necrosis factor-α (TNF-α) in gallbladder tissue; immunohistochemistry was used to measure the protein expression levels of scf and c-kit in gallbladder smooth muscle tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference multiple comparison method was used for further comparison between two groups. Results HE staining showed marked inflammation of gallbladder tissue in the model group, and compared with the model group, the TCM group had a significantly lower degree of inflammation. Western blot showed that the model group had the highest expression level of TNF-α in gallbladder tissue, followed by the TCM group and the normal group ( P < 0.05); immunohistochemistry showed that compared with the model group, the normal group and the TCM group had significantly higher protein expression levels of scf and c-kit in gallbladder smooth muscle tissue ( P < 0.05). Conclusion Dahuang Lingxian prescription can enhance the dynamic function of the gallbladder, possibly by upregulating the scf/c-kit signaling pathway in interstitial cells of Cajal in gallbladder.

OBJECTIVE:To observe the efficacy and safety of Shuxuetong injection in the treatment of acute cerebral infarc-tion (ACI). METHODS:110 patients with ACI were randomly divided into control group and observation group. Control group was given mannitol,aspirin,atorvastatin,antidiabetic drugs and other conventional treatment;observation group was additionally given Shuxuetong injection 6 ml adding into 0.9% Sodium chloride solution 250 ml by intravenous infusion,3 times a day. The ef-ficacy in 2 groups was evaluated after 15 d,and the National Institute of Health Stroke Scale(NIHSS)score,neuron specific eno-lase(NSE),high-sensitivity C-reactive protein(hs-CRP)and tumor necrosis factor-α(TNF-α)levels before and after treatment and the incidence of adverse reactions in 2 groups were recorded. RESULTS:After treatment,NIHSS score,NSE,hs-CRP and TNF-αin 2 groups were significantly lower than before,and observation group was lower than control group,the differences were statisti-cally significant(P<0.05);total effective rate in observation group was significantly higher than control group,the difference was statistically significant(P<0.05). There was no obvious adverse reactions in 2 groups during treatment. CONCLUSIONS:Based on the conventional treatment,Shuxuetong injection has good efficacy and safety in the treatment of ACI.

BACKGROUND:Angiotensin-converting enzyme as a key enzyme of the renin-angiotensin system, through the degradation effects of substance P mechanism, is involved in the occurrence and development of Alzheimer’s disease.
OBJECTIVE:To research the relationship between angiotensin-converting enzyme gene polymorphism and Alzheimer’s disease in Jiamusi region, as wel as the effect of gender and hypertension on the relationship.
METHODS:This case-control study included 96 Alzheimer’s disease patients. Another 102 subjects served as controls coming from the same area and in the same environmental condition. DNA segments were amplified using PCR in 20 g/L agarose gel electrophoresis and observed under ultraviolet lamp. II, ID, DD genotypes and genotype frequencies were calculated for statistical analysis. On this basis, according to clinical data col ected, we investigated association of Alzheimer’s disease with hypertension and gender.
RESULTS AND CONCLUSION:There was significant difference between Alzheimer’s disease patients and controls in angiotensin-converting enzyme genotypes and al ele frequency. There was statistical y significant difference between Alzheimer’s patients with hypertension and controls in angiotensin-converting enzyme genotypes and al ele frequency. There was no statistical difference between Alzheimer’s disease patients with different genders and controls in angiotensin-converting enzyme genotypes and al ele frequency. These findings indicate that there are some relationships between angiotensin-converting enzyme polymorphism and Alzheimer’s disease. II genotype is a risk factor for Alzheimer’s disease, angiotensin-converting enzyme II genotype is a risk factor for Alzheimer’s disease with hypertension.

BACKGROUND:The improvement of athletic achievements needs a super-limited exercise to gain,how to protect athletics health under the prerequisite of gaining excellent achievements?OBJECTIVE:To reduce the injury of athletic renal function following maximum exercise by using traditional Chinese medicinal methodDESIGN:A randomized and controlled trial,taking students majoring in sports education specialty as subjects.SETTING:Internal Medicinal Department of Traditional Chinese Medicine (TCM) Hospital of Qufu Hospital of Traditional Chinese Medicine and Sports Education College of Qufu Normal University.PARTICIPANTS :Two small natural classes were randomly drown up from 16 small natural classes of 2000 grade in Sports Education College of Qufu Normal University, with 20 students in each class, on April 20, 2004.METHODS:All 40 students were according to natural class divided as experimental class and control class.The urine specimens for test were collected 15-20 minutes after one time maximum loading training on April24,2004 and immediately after morning getting-up. The procedure was performed once more on May 24. During the process the students in experimental group had taken the capsule of kidney-and-spleen-strengthening Chinese drug (KSSD, containing mainly Rhizoma Dioscoreae, Radix Polygoni Multiflori, Herba Epimedii, Fructus Lycii, Gynostamma Pentaphyllum,Radix Acanthopanacis Senticosi,Radix Salviae Miltiorrhizae,Radix Bupleuri, etc., 0.3 g/pellet), 6 pellets, 3 times a day. Urinary glucoprotein,β2-microglobulin, albumin and globulin were detectedby radio-immunoassay.MAIN OUTCOME MEASURES:The changes of urinary proteins of the students before and after administration following maximum exercise and getting-up in next morning.RESULTS: All students involved were good for the trial, without any loss.① The contents of various urinary proteins for the subjects after the maximum exercise or before administration were all obviously increased,and the conditions of natural recovery of proteinuria on getting-up next morning were quiet different: the recovery of urinary albumin was the fattest, basically to the normal;recoveries of β2 micro-globulin and immune-globulin were obvious, but the recovery of glucoprotein was inconsiderable.② After the second trial,in comparing the experimental group with the control group it was found that KSSD can obviously influence the recovery of proteinuria following maximum exercise:The effect in 12 hours did not be shown because of too fast natural recovery of albuminuria. It could promote the recoveries of β2 micro-globulin and immune-globulin. The effect on recovery of urinary of glucoprotein was obvious,basically to the normal for experimental group and basically no change for control group,there was a significant differentiation between the two groups.CONCLUSION:The contents of urinary proteins were obviously increased following maximum loading training, and natural recoveries of the four kinds of proteins presented regulatory changes.KSSD can promote the recovery of proteinuria following maximum exercise to normal volume,suggesting that the medicine has a protecting role to renal function.

Objective To investigate the effect of half-body ionizing radiation on the concentration of MDA, SOD in serum and the spleen index, CFU-S and the protective function of supplementary taurine (Tau) in half-body ionizing irradiated mice. Methods Kunming mice were randomly divided into 6 groups: normal control, total-body irradiation (TBI), total-body irradiation+Tau, left-half-body irradiation, half-body irradiation+Tau, and total-body shielding irradiation. The relevant indexes such as the spleen index, spleen colony forming units (CFU-S) were observed. The ionizing radiation was performed under ~ 60 Co ? ray with absorbed dose 8.0 Gy, dose rate 68.46 cGy/min. Taurine at dose of 500 mg/kg was injected intraperitoneally twice a day before irradiation, once 30 min before irradiation, and once 6 h after irradiation. Results In TBI group, the spleen index and CFU-S were decreased remarkably, MDA increased and SOD reduced in serum. The hematopoietic function of spleen was not improved by supplementary taurine (P

Objective To explore the effects of survivin on radiation injury and its relation to caspase 9/6,3 activity. Methods ① IEC 6 cells were treated under hypoxic environment for 8 h and followed by reoxygenation for 24 and 48 h, and then the expression of survivin was identified by Western blotting. ② After treatment with 35 Gy 60 Co , the apoptosis rate in different groups was detected with FACS and the caspase 9/6,3 activity was tested using the caspase 9/6,3 assay kit. Results Hypoxic preconditioning could induce the expression of survivin in IEC 6 cells and survivin could decrease the caspase 3 activity, resulting in reduced apoptosis rate induced by radiation. Conclusion Survivin induced by hypoxic preconditioning can inhibit the apoptosis induced by radiation by reducing the caspase 3 activity.