OBJECTIVE To optimize the management of the China Listed Drug Patent Information Registration Platform as well as to provide guidelines and references for generic drug enterprises to carry out generic research， production and launch in order to further improve the drug patent linkage system. METHODS The used method is to log in and search the National Medical Products Administration （NMPA）， China Listed Drug Patent Information Registration Platform， China National Intellectual Property Administration （CNIPA） and other websites. The search content included the Chinese drug patent declaration system and other legal or policy information， as well as registration data for class 1 drug patent declarations in China. The above data were mined as a whole together with analysis of the varieties with a high composite ranking in the quantity with class 1 declaration； the improvement measures for China’s class 1 declaration system for generic drugs were put forward based on the practice of Chinese pharmaceutical market. RESULTS & CONCLUSIONS Class 1 drug patent declarations of chemical generic drugs accounted for over 99% of the total， and there were 5 varieties among the top 5 in the number of class 1 patent declarations （e.g. Tadalafil tablets， Sodium hyaluronate eye drops）. Based on the analysis of the overall situation and individual cases， it is suggested that China should improve its drug patent linkage system； improve functions of China Listed Drug Patent Information Registration Platform by establishing relief mechanism of right-to-know and ex officio examination； help companies select generic drug varieties timely by strengthening data tracking of generic drug companies during the pending approval period and adding a generic drug variety screening function.

ObjectiveTo explore the effect of Ganoderma leucocontextum ethanol extract (GLE) on silicosis and its potential molecular mechanism using network pharmacology, molecular docking technology and animal experiments. Methods i) The components of GLE were analyzed using ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS) method. The active components, potential molecular pathways and targets of GLE in the intervention of inflammation process of silicosis was explored using network pharmacology and molecular docking technology. ii) Specific pathogen free male C57BL6/J mice were divided into four groups with 10 mice in each group. The mice in the silicosis model group and GLE intervention group were given a dose of 80 μL silica suspension with a mass concentration of 50 g/L once by non-exposed tracheal instillation, and the mice in the blank control group and GLE control group were given an equal volume of sterile 0.9% sodium chloride solution. From the second day after modeling, GLE control group and GLE intervention group were given GLE at a dose of 200 mg/(kg•d) by gavage, while blank control group and silicosis model group were given the same volume of 0.9% sodium chloride solution by gavage, once per day for 35 days. After that, the histopathological changes of lung tissues of mice were observed, the lung mass coefficient, inflammation score and the ratio of collagen deposition area were calculated, and the levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in the lung tissues of mice were detected by enzyme-linked immunosorbent assay. Results i) A total of 76 active components of GLE were detected by UPLC-QE-MS. Among them, 36 ingredients met the screening criteria of the five principles of drug-like components. A total of 67 potential targets of the 36 GLE active ingredients to improve the inflammatory response of silicosis were screened based on the network pharmacology theory. The result of Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Ontology functional analysis showed that IL signaling and cytokine signaling of immune cells played a key role in the process of anti-silicosis of GLE. The results of molecular docking showed that the top 10 targets based on the 67 intersection targets were TNF, IL6, B-cell lymphoma 2, cellular tumor antigen p53, Caspase-3 subunit p12, JUN, epidermal growth factor receptor, IL1B, 67 kDa matrix metalloproteinase-9 and prostaglandin G/H synthase 2. The result of protein-protein interaction analysis showed that glycyrrhetinic acid had the strongest affinity with the key targets TNF-α, IL-1β and IL-6, followed by ganoderma acid DM, alismatol C, ganoderma acid β and red sapogenin. ii) The results of histopathological examination showed that the inflammatory response and collagen deposition were alleviated in the lungs of mice with silicosis. The lung mass coefficient, inflammation score, ratio of collagen deposition area and IL-6 expression in lung were lower in mice of the GLE intervention group (all P<0.05), compared with the silicosis model group. However, there was no significant difference in the levels of TNF-α and IL-1β in lung tissues between the two groups (all P>0.05). Conclusion GLE may reduce silica-induced lung inflammation and fibrosis by inhibiting the IL-6 level in lung tissues of mice. Its mechanism is associated with the synergistic action of multi-components, multi-targets and multi-pathways.

Objective:To explore the effectiveness of applying the ADDIE (analysis, design, develop, implement, evaluate) Model in clinical teaching for nursing interns in spine surgery department.Methods:Using a convenience sampling method, 44 nursing interns in the Department of Orthopedics at Peking Union Medical College Hospital were selected as the control group from July 2021 to May 2022, and were taught using traditional methods. From July 2022 to May 2023, 45 nursing interns were selected as the observation group, and a teaching team was formed to design a training program based on the five stages of the ADDIE instructional design model. This program was tailored to improve the overall clinical competence of the spinal surgery nursing interns. After training, the teaching effects were evaluated based on knowledge test scores, skills test scores, overall clinical competence, and teaching satisfaction.Results:After the training, the skills test scores in specialized nursing for the observation group were (94.87±1.10) points, higher than the control group's (93.98±1.41) points, with a statistically significant difference ( P<0.01). The observation group also scored higher than the control group in clinical judgment, organizational effectiveness, overall performance, and total score in the Mini-Clinical Evaluation Exercise, with statistically significant differences ( P<0.01). Additionally, the observation group reported higher satisfaction with the teaching plan and methods compared to the control group ( P<0.05) . Conclusions:Clinical teaching for spinal surgery nursing interns based on the ADDIE instructional design model can improve their specialized practical skills and overall clinical competence. The interns also expressed a high level of acceptance for this teaching design model.

The development of obesity is closely related to the disruption of central appetite regulation. Gastric growth hormone-releasing peptide is the only appetite-promoting peptide known to be present in the circulatory system. Ghrelin may act on the central homeostatic and hedonic feeding neural pathways to promote appetite and feeding behavior, and may be a new target for appetite regulation. In addition, Ghrelin is also involved in the regulation of energy homeostasis via promoting growth, regulating gastrointestinal function, and suppressing inflammatory response. Therefore, the research on the mechanism of ghrelin and its receptors will help understand the pathophysiological changes in the central appetite regulation process of obese patients, and to find potential targets for the treatment of obesity. In this paper, we focus on the molecular mechanism of appetite regulation by Ghrelin and its clinical application.

To evaluate the clinical effects and pathological characteristics of gastric tumors of fundic gland type treated with endoscopic submucosal dissection (ESD), data of 7 patients who treated by ESD and whose postoperative pathology indicated gastric adenocarcinoma of fundic gland type or gastric oxyntic gland adenoma in Endoscopic Center of Beijing Chao-Yang Hospital of Capital Medical University from August 2018 to June 2022 were collected. The clinical characteristics, surgical complications, preoperative and postoperative pathological data and follow-up data were evaluated. The lesions of the 7 patients were all located at gastric fundus, and were treated by ESD successfully. No bleeding, perforation or other complications occurred during and after the operation. Postoperative pathology showed that tumor cells originated from deep mucosa with an invasive growth pattern. Most of tumor surfaces were covered with normal concave epithelium. Tumors infiltrated into submucosa in 4 patients, and submucosa infiltration depth was more than 500 μm (550 μm) in 1 patient. Immunohistochemistry showed that MUC-6 was diffusely positive, indicating that the tumor originated from the main cell source. The expressions of MUC-2, MUC-5AC, CDX-2, CD10, and CgA were negative in all cases. With the mean follow-up time of 21 months, the ulcer healed well after the operation, with no recurrence. Gastric tumors of fundic gland type have relatively unique biological characteristics, and ESD is the preferred treatment. In addition, the histological characteristics can be used to differentiate from other gastric tumors by immunohistochemistry.

Objective:To investigate the predictive value of serum vascular endothelial growth factor (VEGF), squamous cell carcinoma-associated antigen (SCCAg) and miRNA let-7a in lymph node metastasis and postoperative recurrence in patients with laryngeal cancer.Methods:A total of 82 patients with laryngeal cancer in the Second Central Hospital of Baoding from November 2017 to October 2019 were selected as the research subjects, including 18 cases of lymph node metastasis (metastasis group) and 64 cases of non metastasis (non metastasis group). The blood routine was tested before operation, and the baseline data, serum VEGF, SCCAg and miRNA let-7a levels were compared between the two groups. Logistic regression was used to analyze the related influencing factors of lymph node metastasis in patients with laryngeal cancer. The correlation between serum VEGF, SCCAg, miRNA let-7a levels and clinicopathological characteristics was analyzed. The receiver operating characteristic (ROC)curve was used to analyze the value of each index and the combined diagnosis of lymph node metastasis in patients with laryngeal cancer. After 1 year of follow-up, the serum VEGF, SCCAg and miRNA let-7a levels of patients with or without recurrent laryngeal cancer were compared. ROC curve was used to evaluate the value of VEGF, SCCAg, and miRNA let-7a in predicting the recurrence of laryngeal cancer.Results:There were statistically significant differences in tumor node metastasis (TNM) stage, degree of infiltration, degree of differentiation, serum VEGF, SCCAg, and miRNA let-7a levels between the metastasis group and non metastasis group (all P<0.05). Serum VEGF, SCCAg, miRNA let-7a levels in patients with laryngeal cancer were related to TNM stage, degree of infiltration and degree of differentiation (all P<0.05). The combined diagnosis of serum VEGF, SCCAg and miRNA let-7a levels in the diagnosis of lymph node metastasis in patients with laryngeal cancer showed that the diagnostic sensitivity and specificity were 88.89% and 70.31%, respectively. The serum VEGF and SCCAg levels of patients with recurrence after operation were higher than those without recurrence, and the level of miRNA let-7a was lower than those without recurrence (all P<0.05). The sensitivity and specificity of combined serum VEGF, SCCAg and miRNA LET-7a levels in predicting postoperative recurrence of laryngeal cancer were 72.97% and 91.11%, respectively. Conclusions:VEGF, SCCAg, miRNA let-7a in patients with laryngeal cancer have a certain correlation with clinicopathological characteristics, which can assist in the diagnosis of lymph node metastasis and help clinical prediction of postoperative recurrence in patients with laryngeal cancer, and provide a reference for the formulation of clinical treatment plans.

Gastric cancer is one of the most common malignancies and is the third leading cause of cancer-related deaths worldwide, constituting a serious threat to human health. Long non-coding RNA (lncRNA) is involved in the occurrence and development of gastric cancer at multiple levels and plays critical regulatory roles. It plays important roles in the diagnosis, treatment and prognostic assessment of gastric cancer. This review focuses on the recent research advances in the clinical applications of lncRNA in gastric cancer.

Objective To compare curative effect between lenvatinib combined with locoregional therapy and locoregional therapy on PD-L1-positive hepatocellular carcinoma patients with type Ⅰ-Ⅲ portal vein tumor thrombus according to Cheng's classification. Methods The patients in lenvatinib combined with locoregional therapy group received orally-administered lenvatinib at a dose of 12 mg qd for patients≥60 kg or 8 mg qd for patients < 60 kg. The locoregional therapy group only received locoregional therapy. We retrospectively analyzed the clinical data and prognosis of two groups. Results The CR+PR were 78.1% and 53.6% in the combination group and locoregional therapy group, respectively (P < 0.05). The response rate, disease control rate and overall survival of the combination group were higher than those in the locoregional therapy group (P < 0.05). Conclusion The curative effect and overall survival of lenvatinib combined with locoregional therapy is better than locoregional therapy on PD-L1-positive hepatocellular carcinoma patients with type Ⅰ-Ⅲ portal vein tumor thrombus according to Cheng's classification.

In 2020, two formulations of botulinum toxin type A (BoNT-A)named AbobotulinumtoxinA(Dysport ?) and LetibotulinumtoxinA(Letybo ?) have been officially approved by National Medical Products Administration to come on the market. To compare BoNT-As with different formulations, three BoNT-As[AbobotulinumtoxinA, OnabotulinumtoxinA(Botox ?), IncobotulinumtoxinA(Xeomin ?)] with relatively more clinical evidences internationally and two domestic BoNT-As[LanbotulinumtoxinA(Prosigne ?), LetibotulinumtoxinA] were included. Diffusion scale, conversion ratio, onset, duration and immunogenicity of different BoNT-As were reviewed in detail to provide reference for clinical practice.

In 2020, two formulations of botulinum toxin type A (BoNT-A)named AbobotulinumtoxinA(Dysport ?) and LetibotulinumtoxinA(Letybo ?) have been officially approved by National Medical Products Administration to come on the market. To compare BoNT-As with different formulations, three BoNT-As[AbobotulinumtoxinA, OnabotulinumtoxinA(Botox ?), IncobotulinumtoxinA(Xeomin ?)] with relatively more clinical evidences internationally and two domestic BoNT-As[LanbotulinumtoxinA(Prosigne ?), LetibotulinumtoxinA] were included. Diffusion scale, conversion ratio, onset, duration and immunogenicity of different BoNT-As were reviewed in detail to provide reference for clinical practice.