Objective The study aims to optimize the conditions for constructing orthotopic nude mouse models of liver cancer by injecting human liver tumor cell lines and to explore appropriate timings for drug administration. Methods Human hepatocellular carcinoma Hep3B and hepatoblastoma HepG2 cell lines, which stably expressing the luciferase reporter gene (LUC), were selected. The linear correlation between the luciferase luminescence intensity and the number of liver tumor cells was analyzed using a Small Animal In Vivo Imaging system to verify the luminescent efficiency of the human liver tumor cells. Different concentrations (8×10⁶, 2.4×10⁷, 7.2×10⁷ cells/mL) and resuspension media (PBS, Matrigel) of human liver tumor cell suspensions HepG2-LUC and Hep3B-LUC were orthotopically inoculated into the liver lobes of 5-week-old female BALB/c nude mice (12 groups, 7 mice each) to construct human liver tumor nude mouse orthotopic cancer models. Every 7 days, the weights of mice were recorded, and the growth of orthotopic tumors was monitored using the Small Animal In Vivo Imaging system. On day 35 post-cell inoculation, mouse livers were dissected, and pathological slices were prepared for HE staining to observe histopathological changes in liver tissues. Results The luminescence intensity of human liver tumor cell lines was positively correlated with the number of cells (R²=0.983 1, R²=0.970 5), indicating their suitability for orthotopic model construction. Successful modeling was achieved in the high-concentration groups of HepG2-LUC, the low-, medium-, and high-concentration groups of HepG2-LUC+Matrigel, the medium- and high-concentration groups of Hep3B-LUC, and the low-, medium-, and high-concentration groups of Hep3B-LUC+Matrigel. For both HepG2-LUC+Matrigel and Hep3B-LUC+Matrigel groups, mice in the high-concentration groups exhibited significantly reduced body weight compared to the low- and medium-concentration groups (both with P<0.05). The luminescence intensity of successfully modeled mice increased exponentially over time (R²>0.950 0), and reached a minimum of 1.0×10⁷ p/(s·cm²·sr) by day 14 post-transplantation. Mice in the low- and medium-concentration groups of HepG2-LUC and the low-concentration group of Hep3B-LUC showed no significant pathological changes, while the other groups exhibited evident liver tumors and hepatocyte lesions. Conclusion For the HepG2-LUC cell line, the recommended injection volume is 50 µL with a cell density of 2.4×10⁷ cells/mL, resuspended with Matrigel, followed by drug administration or prognostic measures on day 7 post-modeling. For the Hep3B-LUC cell line, the recommended injection volume is 50 µL with a cell density of 7.2×10⁷ cells/mL, not resuspended with Matrigel, with administration or prognostic measures on day 14 post-modeling.

Objective The study aimed to elucidate the evolution of the syndromes in Traditional Chinese Medicine(TCM)and TCM syndrome elements in different chronic stages of psoriasis vulgaris.Methods A database was constructed using electronic medical records collected from July 2019 to March 2024 from 1,049 patients with psoriasis vulgaris.The study used Sankey diagrams and network association graphs to analyze the evolution of TCM syndromes and their elements in patients at the different stages:initial diagnosis,progressive stage(Week 2-3),progressive stage(Week 4-5),skin lesion improvement stage(Week 6-7),and remission stage.The syndrome elements network was constructed using community detection algorithms,and the association rules between local skin lesion syndrome differentiation and overall syndrome differentiation were displayed using heatmaps.Results(ⅰ)Initial diagnosis.In the syndrome differentiation of local skin lesions,blood heat syndrome was the most common(79.79％);among the disease location of TCM syndrome elements(called"disease location"),liver was the most prevalent(35.62％);and among the pathological factors of TCM syndrome elements(called"pathological factors"),fire(heat)was the most common(75.48％).(ⅱ)Active stage(Week 2-3).In the syndrome differentiation of local skin lesions,blood heat syndrome remained the most prevalent(73.13％);among the disease location,liver was still the most prevalent(31.71％);and among the pathological factors,fire(heat)continued to be the most common(82.11％),while dampness(22.26％)and qi stagnation(8.39％)began to increase.(ⅲ)Active stage(Week 4-5).The syndrome differentiation of local skin lesions was dominated by blood heat syndrome(45.91％)and blood dryness syndrome(37.19％);among disease location,the interior was the most prevalent(15.25％);and among the pathological factors,fire(heat)remained the most common(50.66％),with an increase in yin deficiency(34.26％).(ⅳ)Skin lesion improvement stage(Week 6-7).In the syndrome differentiation of local skin lesions,both blood dryness syndrome(49.44％)and blood stasis syndrome(33.33％)increased;among the disease location,meridians increased most significantly and became the most prevalent(13.44％);and among the pathological factors,blood stasis increased most significantly and became the most prevalent(28.20％).(ⅴ)Remission stage.In the syndrome differentiation of local skin lesions,blood stasis syndrome became the primary(55.69％),while the percentage of blood dryness syndrome decreased(21.16％);meridians(25.71％)and blood stasis(62.34％)remained the most predominant syndrome elements related to disease location or pathological factors.Conclusion The overall pattern of TCM syndromes in psoriasis vulgaris evolved from excess to deficiency.From the initial diagnosis to the active phase(Week 2-3),heat syndrome dominated;during the active phase(Week 4-5),heat syndrome coexisted with damp syndrome or yin deficiency syndrome;changes in the syndrome element network were the most significant during the lesion improvement phase,with blood stasis gradually increasing and peaking during the remission phase.Blood stasis,dampness,and qi stagnation were pervasive throughout psoriasis vulgaris;qi stagnation and blood stasis may be the main elements causing further deterioration and prolonged course of the disease during the active phase in patients.

Objective To investigate the efficacy and safety of artificial liver support therapy with an Evanure-4A selective membrane plasma separator and its influence on platelet count in the treatment of patients with acute-on-chronic liver failure(ACLF)patients with different platelet counts.Methods A total of 302 patients with ACLF who were hospitalized in Department of Hepatology,Chengdu Public Health Clinical Medical Center,from January 2021 to May 2023,were enrolled,and according to the platelet count(PLT),they were divided into group A(25×109/L—50×109/L)with 101 patients,group B(51×109/L—80×109/L)with 98 patients,and group C(81×109/L—100×109/L)with 103 patients.In addition to medical treatment,all patients received different modes of artificial liver support therapy based on their conditions,including plasma perfusion combined with plasma exchange,double plasma molecular adsorption combined with plasma exchange,and bilirubin system adsorption combined with plasma exchange.The paired t-test was used for comparison of continuous data before and after treatment in each group;an analysis of variance was used for comparison between multiple groups,and the SNK-q test was used for further comparison between two groups;the chi-square test was used for comparison of categorical data between multiple groups.Results Of all 302 patients,268(88.74%)achieved varying degrees of improvement in clinical symptoms after artificial liver support therapy.After treatment,all three groups had varying degrees of reductions in alanine aminotransferase(t=14.755,21.614,and 15.965,all P＜0.001),aspartate aminotransferase(t=11.491,19.301,and 13.919,all P＜0.001),total bilirubin(t=19.182,17.486,and 21.75,all P＜0.001),and international normalized ratio(INR)(t=3.497,3.327,and 4.358,all P＜0.05).After artificial liver support therapy with an Evanure-4A selective membrane plasma separator,PLT in group A decreased from(37.73±6.27)×109/L before treatment to(36.59±7.96)×109/L after treatment,PLT in group B decreased from(66.97±7.64)×109/L before treatment to(62.59±7.37)×109/L after treatment,and PLT in group C decreased from(93.82±5.38)×109/L before treatment to(85.99±12.49)×109/L after treatment;groups B and C had significant reductions in PLT after treatment(t=12.993 and 8.240,both P＜0.001),but there was no significant difference in group A(P＞0.05).There was no significant difference in the incidence rate of adverse reactions during artificial liver support therapy between the three groups(P＞0.05).Conclusion Artificial liver support therapy can improve liver function and INR in patients with ACLF.The use of Evaure-4A selective membrane plasma separator during artificial liver support therapy has little influence on platelets,and it is safe in the treatment of ACLF patients with a significantly lower level of platelets.

Objective:To explore the talent cultivation model of nursing professional group under the 1+X certificate system, to build a talent cultivation system for nursing professional groups with "three progressions, four integrations, and five cocultivation"Methods:From 1 July 2021 to 31 December 2023, built a professional group course system of "mutual sharing of foundations, mutual generation of majors, mutual selection of positions, and progressive improvement of abilities". Aligned course content with X certificate content. Deepen the reform of the three education systems, create a "dual teacher" teaching team that combines full-time and part-time work, and build teaching resources that connect the cloud and the ground. The application effect of this model was evaluated in 2021 nursing majors in Cangzhou Medical College by cluster sampling.Results:There were 748 students majoring in nursing in class of 2021, 150 boys aged 19-22(20.00 ± 1.23), 598 girls, aged 19-21(19.00 ± 2.57). There were 118 students majoring in midwifery in class of 2021, all of them were girls, aged 18-20(18.00 ± 2.11). There were 128 students majoring in rehabilitation therapy technology in class of 2021, 66 boys aged 19-21(19.00 ± 2.11), 62 girls aged 19-21(19.00 ± 2.54). Nursing professional group completed the "Basic Nursing Technology Training Guidance", "Elderly Care" and other 5 self-compiled textbooks, 730 students had participated in the X certificate assessment, 729 students e passed the assessment, the passing rate was 99.9%.Conclusions:The talent cultivation model of "three progressions, four integrations, and five co cultivation" in the nursing professional group can cultivate students′ professional abilities, and cultivate a composite technical and skilled talent with multiple abilities and interconnections in one job.

Objectives:To observe the incidence of residual shunt post patent foramen ovale(PFO)closure and the effect of PFO closure in these migraine patients at one year after PFO. Methods:This retrospective study included patients who underwent PFO closure for migraine in the Second Affiliated Hospital Zhejiang University School of Medicine from January 2019 to June 2022,patients were divided into the grade 0 shunt group(n=67),the grade Ⅰ shunt group(n=10),the grade Ⅱ shunt group(n=13)and the grade Ⅲ shunt group(n=16)according to the results of contrast transthoracic echocardiography(cTTE)at 1 year after PFO closure.The incidence of postoperative migraine attacks among different groups of patients were compared.The risk factors of residual shunt after PFO closure were explored. Results:The mean age of enrolled 106 patients with migraine was(35.80±11.70)years,of which 83 patients(78.30%)were female.One year after PFO closure,the migraine attack and rating scale were significantly decreased compared to baseline in the grade 0 shunt group,in the grade Ⅰ shunt group and in the grade Ⅱ shunt group(all P<0.05),but not in the grade Ⅲ shunt group(P>0.05).The rate of significant and complete migraine was significantly higher in the grade 0 shunt group(58.21%),in the gradeⅠ shunt group(60.00%),in the grade Ⅱ shunt group(69.23%)as compared to the grade Ⅲ shunt group(18.75%,P=0.02)at one year after PFO.The rate of grade 0 shunt after PFO closure in patients with the microvesicles appearing in≥6 cardiac cycles in resting state before operation was significantly lower than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles in resting state(24.00%vs.83.87%vs.70.00%,P=0.04).Logistic multivariate regression analysis showed that patients with microvesicles appearing beyond 6 cardiac cycles in resting state were more likely to have residual shunts in postoperative cTTE compared to the patients with negative cTTE and microvesicles appearing within 6 cardiac cycles in the cTTE in resting state before operation(OR=0.06,95%CI:0.02-0.23,P<0.01;OR=0.014,95%CI:0.05-0.41,P<0.01). Conclusions:Migraine patients who underwent PFO closure and with grade 0 to grade Ⅱ residual shunt at one year after PFO are most likely to have significant remission of migraine,while the incidence of migraine remission is low in patients with grade Ⅲresidual shunt.The incidence of residual shunt after PFO closure is higher in patients with the microvesicles appearing in 6 cardiac cycles in resting state in the cTTE before operation than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles.

Objective:To summarize the clinical, pathological and muscle magnetic resonance imaging (MRI) features of human immunodeficiency virus (HIV)-associated nemaline myopathy (NM; HIV-NM).Methods:The present patient was a 23-year-old man with HIV infection who developed progressive proximal weakness and atrophy for more than 10 months. He was admitted to the Department of Neurology of Beijing Ditan Hospital in early June 2021. Electromyography showed myogenic findings. The serum creatine kinase was 202.4 U/L. CD 4+ count was 585×10 6/L. Serum monoclonal immunoglobulin (M protein) was negative. The patient underwent MRI examination of bilateral thigh muscles, biopsy of left biceps brachii and gene detection. The clinical, pathological and muscle MRI changes of HIV-NM were summarized based on the literature review. Results:MRI examination of bilateral thigh muscles showed edema changes. Muscle biopsy showed nemaline structures in some muscle fibers, accompanied by fiber atrophy and regeneration. No gene mutation related to clinical phenotype was found by second-generation sequencing. After intravenous immunoglobulin combined with prednisone, the patient′s weakness symptoms were significantly improved. A total of 17 cases of HIV-NM (including the present case) were identified in the literature, who were aged (33.7±9.1) years. Fifteen were males and two were females. All patients developed proximal limb weakness. Creatine kinase was normal or slightly elevated. Serum monoclonal protein was positive in 3 cases (3/7). Immunosuppressive therapy was effective.Conclusions:The main clinical characteristics of HIV-NM are progressive proximal limb weakness and muscle atrophy. The muscle pathology shows a large number of nemaline structures in atrophic muscle fibers. Muscle edema can be seen on muscle MRI. This is the first report of HIV-NM in China, which may be a special subtype of immune myopathy.

Objective:To report a SPTLC2 gene mutation in a family with a phenotype of Charcot-Marie-Tooth disease.Methods:To screen the family of patients with pathogenic mutations of SPTLC2 gene from the database of hereditary peripheral neuropathy in the Department of Neurology, Peking University First Hospital, and to collect their clinical data, peripheral nerve conduction examination, nerve ultrasound examination, pathological examination of the peroneal nerve and whole exome sequencing results of prohand.Results:One family was screened, the proband was a 16-year-old female with 4 years of sensory loss and anhidrosis of both lower limbs and 16 months of walking difficulty who admitted to Peking University First Hospital in January 2022. Physical examination showed sensory loss, dry skin and weakness in distal limbs. Her father had numbness and dry skin in the distal lower limbs from childhood,weakness and atrophy of his lower limbs in adulthood. He died at age of 52 years old. The nerve conduction study revealed no action potentials of the sensory and motor nerves of the lower limbs in the proband. The amplitude of the compound muscle action potential of the motor conduction of the bilateral ulnar nerve and median nerve decreased, and the nerve conduction velocity of the bilateral median nerve were 32 m/s and 24 m/s. Neurosonography showed thickening of peripheral nerves. Sural biopsy revealed severe loss of myelinated and unmyelinated nerve fibers with onion bulbs formation. SPTLC2 gene showed a known heterozygous p.G435V mutation. The lower limb weakness was improved after oral L-serine.Conclusions:SPTLC2 gene mutation can lead to an intermediate Charcot-Marie-Tooth disease phenotype. L-serine can improve the limb weakness.

Objective:To explore a new training mode for nursing professionals suitable for the 1+X certificate system, and realize the training goal of "one specialty and multi-ability" compound technical nursing talents.Methods:To take the "1+ X" certificate standard as the basis for the construction of nursing specialty, to reconstruct the talent training program of integration of graduation certificate and certificate. To take the content of "1+X" certificate as the basis for the construction of professional courses, construct the core curriculum system of integration of curriculum and certificate. To build a "new double-qualified" teaching staff and constructing of new double-qualified teachers and accelerate the development of quality resources.Results:The talent training mode of integration of graduation certificate and certificate under the 1+X certificate system was constructed. The curriculum structure has been optimized. The teachers′ability of teaching, training and examination was improved.Conclusions:The new mode of training nursing professionals under the 1+X certificate system meets 1 degree education and X vocational training of nursing students and achieve a "1" and "X" seamless convergence. It provides innovative ideas for the promotion and implementation of 1+X certificate system pilot work in the field of nursing education nationwide.

Objective: To analyze the diagnostic value of skeletal muscle biopsy in patients with rhabdomyolysis. Methods: Clinical and pathological data of 26 patients with rhabdomyolysis from January 2002 to December 2018 undergoing muscle biopsy were collected. Results: Eighteen males and 8 females were finally recruited with median age of 6-73 (37.3±19.6) years. The average time from onset to biopsy was 44 days (median course was 30 days). All patients had acute manifestations with muscle pain and/or weakness. Serum creatine kinase was between 1 648-92 660 U/L. Muscle biopsies showed nonspecific changes in 12 cases (a few with type 2 muscle fiber atrophy, slight deposition of lipid droplets), 10 cases with necrotizing myopathy (muscle fiber necrosis and regeneration). Toxic neurogenic damages were seen in 2 cases (type 1 and type 2 angular atrophic muscle fibers with group change), lipid storage disease in 1 case (lipid droplets deposit significantly) and idiopathic inflammatory myopathy in 1 case (muscle fiber necrosis and regeneration, with lymphocyte infiltration). The etiology of non-specific pathological changes included short-term strenuous exercise in 6 patients, poisoning in two, chronic kidney disease in one, viral infection in one, hypothyroidism in one and unknown reason in one. As to patients with necrotizing myopathy, seven were poisoning or drug-related, one with hyperthyroidism, two with unknown reason. Conclusions Among the numerous causes of rhabdomyolysis, exercise usually links nonspecific skeletal muscle changes and poisoning or drug-related disorders are commonly associated with necrotic myopathy. Rhabdomyolysis induced by primary myopathy is rare.

Objective: To explore the genetic cause for abnormal pregnancies through detecting chromosomal copy number variations (CNVs) in abortic tissues by next generation sequencing (NGS). Methods: NGS technique was used to detect CNVs in abortion tissues. Parental chromosomal karyotypes were predicted based on the results. The aberrant chromosomal segments of the parents were accurately mapped by G-banding karyotyping analysis and fluorescence in situ hybridization (FISH). Results: In addition to numerical chromosomal aberrations, 12 microdeletion/microduplications were detected by NGS. For 8 families where both parents accepted chromosomal karyotyping, 4 carriers of chromosomal abnormalities were identified. One marker chromosome was missed by karyotyping analysis, and a mother was confirmed to carry a cryptic balanced translocation by FISH. Conclusion NGS can facilitate detection of cryptic chromosomal translocations in couples with repeated pregnancy failure and is of great value for detecting abnormal CNVs for its high sensitivity.