Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

Objective:To explore the surgical treatment of lateral condylar fracture of the humerus combined with lateral dislocation of the elbow in adults.Methods:A retrospective study was conducted to analyze the 8 patients who had been treated at Department of Orthopaedic Trauma, Zhengzhou Orthopaedic Hospital for lateral condylar fracture of the humerus combined with lateral dislocation of the elbow from June 2020 to June 2023. There were 3 males and 5 females, with an age of (50.1±12.3) years. All the lateral condylar fractures of the humerus combined with lateral dislocations were treated by open reduction and internal fixation after swelling subsided. Flexion and extension of the elbow and rotation of the forearm were recorded at the last follow-up. Mayo elbow function score (MEPS) was used to evaluate the functional recovery of the elbow.Results:Elbow dislocation was corrected in 2 patients after rectification, but the elbow subluxation still existed because the displacement of the humeral lateral condyle was not reduced. The elbow dislocation still existed in 6 patients because it was difficult to maintain the correction of the dislocation after manual reduction. Follow-ups were conducted for 12.0 (12.0, 18.8) months. At the last follow-up, the flexion-extension was 85.6°±20.3°, rotation 133.1°±24.0°, and MEPS (91.9±8.0) points. The joint stability was significantly improved in the 8 patients compared with that before operation. Obvious pain was reported in none of the patients, and their joint limitation was acceptable.Conclusions:In adults, lateral condylar fracture of the humerus combined with lateral dislocation of the elbow is rare in clinic. Surgical treatment of the condition can achieve satisfactory clinical outcomes, but elbow dysfunction and limited rotation of the forearm may occur in the affected limb.

Production internship is an important teaching tache for undergraduate students to carry out engineering training by using professional skills, and it is a key starting point for fostering application-oriented talents in biotechnology. The Course Group of 'production internship of biotechnology majors' of Binzhou University is investigating application-oriented transformation for local regular colleges and universities, as well as fostering high-level application-oriented talents. By taking green fluorescent protein (GFP) polyclonal antibody as an example, the reform and practice on teaching content, teaching mode, assessment method, continuous improvement of curriculum were carried out. Moreover, the characteristics of the Yellow River Delta-Binzhou Biotechnology & Pharmaceutical Industrial Cluster were taken into account to intensify academic-enterprise cooperation. On one hand, this Course Group designed and rearranged the course contents, carried out essential training through online resources and platforms such as virtual simulation, and recorded, tracked and monitored the progress of production internship through practical testing and software platforms like 'Alumni State'. On the other hand, this Course Group established a practice-and application-oriented assessment method in the process of production internship and a dual evaluation model for continuous improvement. These reform and practices have promoted the training of application-oriented talents in biotechnology, and may serve as a reference for similar courses.
Humans ; Internship and Residency ; Curriculum ; Students ; Biotechnology

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both

Objective: To investigate the clinical features and pathogenic genes of a family with osteosclerosis. Methods: Six patients and six family members from a family in Jiangsu were tested for biochemical parameters, bone metabolic markers, bone mineral density, thoracolumbar anterior lateral slices, skull positive lateral radiographs, and pelvic plain films. Meanwhile, Sanger sequencing was performed to detect gene mutations of the proband and five other family members with high bone mass. The conformation of the mutational low-density lipoprotein receptor-related protein 5 (LRP5) protein was predicted by SWISS-MODEL. Results: Four adult patients (one male and three females) were tall, with mandibular enlargement and kyphosis in the center of the lower jaw, and none of the four had fractures. Their X ray examination revealed that the skull and long bone cortex was thickened, while the sella and mandible was enlarged. In addition, the absolute values of bone mineral density at each site of all patients were significantly higher as compared with the standard age- and sex-matched adults or adolescent mean reference values, with Z scores of L2-4, femoral neck and total hip being (6.31±4.03) SD, (6.56±2.36) SD, and (7.19±2.03) SD, respectively. The results of genetic sequencing revealed that all six patients carried a heterozygous mutation (c.331G>T; D111Y) in exon 2 of LRP5 gene, while other family members showed wild type (c.331G>G; D111D). Functional prediction indicated that this mutation was located at the amino acid terminal of exon 2 of LRP5 gene, which encodes the first β-helix-generating region of LRP5 protein. Conclusion The D111Y mutation in LRP5 gene leads to a clinical phenotype characterized by benign increased bone mineral density without increasing the risk of fracture. This mutation may further affect the downstream Wnt signaling pathway by altering the spatial structure of LRP5 protein, thereby promoting maturation and differentiation of osteoblasts and resulting in osteosclerosis.

Objective To investigate the correlations between the FBN1 gene mutation types and the clinical phenotype . Methods 87 probands with Marfan or Marfan-like syndromes and their family members were enrolled in this study ( total 300 cases).The clinical manifestations of each patients involving the ocular, cardiovascular system, skeletal system and other im-plicated systems were collected and evaluated .According to the clinical manifestations , these patients were divided into two groups, namely aortic dissection group and aortic root aneurysm group.Blood samples were taken from patients and DNA se-quencing was performed on each patient by the genetic aortic disease gene Panel .The detected single nucleotide variants ( SNVs)/indel were interpreted according to the ACMG guidelines, and the pathogenic variation was confirmed through Sanger sequencing.The aortic wall tissue was obtained from MFS patients who underwent surgery .The correlations between genotypes and clinical phenotypes were further explored by comparing the aortic wall tissue histological specimens of each genotype pa-tient.Results A total of 92 FBN1 mutations(31％) were detected in 300 people with Marfan syndromes or Marfan-like syn-dromes, 18 of which were undiscovered mutations.There were 49 missense mutations(53.26％), 13 splicing mutations (14.13％), 17 frameshift mutations(18.48％), and 13 nonsense mutations(14.13％).In this cohort, 24 cases had aortic dissection and 25 cases were aortic root aneurysm.Statistical analysis revealed that patients with aortic dissection mostly ap-peared in frameshift mutations(29.17％ vs.4.00％, P =0.017).However, patients with aortic root aneurysm mostly ap-peared in missense mutations(72.00％ vs.37.50％, P =0.015), and accompanied with ectopia lentis(41.67％ vs. 8.33％, P=0.008).Pathological specimens staining found that elastic fibers in the aortic wall of patients with frameshift mu-tations are sparser, and the smooth muscle cells are more deficient and more disorganized than patients with missense muta-tions.Conclusion FBN1 gene frameshift mutations result a lack of elastic fibers and disorganized smooth muscle cells in aor-tic wall and are presented more in patients with aortic dissection than aortic root aneurysm .

Objective To understand the genetic variations of neuraminidase (NA) genes of avian influenza virus H9N2 in Weining,Guizhou Province,and to provide the scientific evidence for the prevention and control of avian influenza virus.Methods Ribonucleic acids (RNA) were extracted and NA genes were amplified and sequenced from 13 randomly selected H9N2 positive samples from the live poultry market (LPM)environments in north of Weining Yi and Hui and Miao autonomous county (Weining),Guizhou Province during 2015 to 2017.Then the homology,genetic evolution,and sites of stalk deletion areas,potential N-glycosylation,receptor binding regions and drug resistance of H9N2 subtype avian influenza viruses were analyzed by a series of bioinformation software.Results Homology analysis revealed that there were 93.0％-100.0％ and 92.1％-100.0％ similarity among 13 strains H9N2 avian influenza viruses in nucleotide and amino acid of the NA gene,respectively.All strains belonged to DK/HK/Y280/97 sub-lineage,but their genetic sources were complex and diverse.Thirteen strains had a stalk deletion of 3 amino acid residues TEI at positions 63-65 and 3 isolates had mutation QN to QK at positions 39-40.The potential N-glycosylation sites at amino acid residues 86,146,200,and 234 of the NA protein of all strains were highly conserved,while other N-glycosylation sites had quantity and site mutations.There were different mutation types at the three sialic acid binding site areas,especially at 399-404 area.All NA protease activity sites and key sites of the 13 strains had no mutations associated with resistance to the neuraminidase inhibitor drugs.Conclusions All 13 strains H9N2 viruses belongs to DK/HK/Y280/97 sub-lineage in Weining,Guizhou Province during 2015-2017,and their genetic sources are complex and diverse.The mutations on sites of stalk areas,potential N-glycosylation and sialic acid binding site areas are presented at different degrees.Hence,enhancing surveillance and controlling H9N2 avian influenza virus is necessary.

Objective: To evaluate the changes of volume and mass of pulmonary nodules which were detected in low-dose computed tomography (LDCT) screening, and to analyze the influencing factors. Methods: This retrospective study analyzed the CT images of the participants who underwent at least two chest LDCT scanning from March 2009 to December 2015 in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The inclusion criteria was the nodule diameter ≥6 mm; the volume growth was defined as ≥20%. Fifty-one pulmonary nodules (PNs) were selected among 51 enrolled participants (26 men and 25 women). According to characteristic of nodule and risk stratification of participant, the nodules were classified into different groups (10 non-solid nodules, 17 part-solid nodules and 24 solid nodules; 14 PNs in high-risk group, 12 PNs in moderate-risk group and 25 PNs in low-risk group). The Lung-VCAR software was used to measure the diameter and volume of the PNs, and all nodules were calculated for the volume doubling time (VDT) and mass doubling time (MDT). Results: Among the 51 PNs, the diameter of 33 nodules increased more than 1.5 mm while 18 nodules increased less than 1.5 mm. The median VDT of part-solid nodules was 364 days, which was shorter than that of non-solid nodules and solid nodules (761 and 819 days, respectively), the differences were statistically significant (both P<0.05). The median MDT of part-solid nodules was 351 days, which was lower than that of non-solid nodules and solid nodules (772 days and 840 days, respectively). The difference was statistically significant (P<0.05). The median VDT and MDT of the pulmonary nodules in the high-risk group were 181 days and 256 days, respectively, which were lower than those in the low risk group (1 037 days and 1 035 days, respectively). VDT has good correlation with MDT (r=0.909, P<0.001). Conclusions Both the characteristic of PNs and the risk status of the participants could affect the growth of nodules in LDCT screening. The part-solid nodules and high-risk group nodules grew relatively faster, which should be closely focused on. Compared with the two-dimensional diameter, the three-dimensional quantitative indicators (VDT and MDT) were more sensitive for nodule growth. The mass changes of part-solid nodules were earlier than that of volume.