OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform， and to evaluate the effectiveness of the reform， thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis， the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment， training， assessment， and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency， with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform， the new training system and model became increasingly mature. In both 2023 and 2024， the participants achieved relatively high average total scores in their initial completion assessments [with scores of （84.05± 5.83） and （85.82±4.35） points， respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of （4.80±0.44） and （4.85±0.39） points， respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future， clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase， while aligning with global trends in pharmacy education and industry development. Additionally， sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.

ObjectiveTo observe the effects of Hei Xiaoyaosan on the learning and memory abilities of Alzheimer's disease model mice （APP/PS1 mice）， and to explore its mechanism through the inflammatory cascade mediated by nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 （NLRP3）/cysteine aspartate-specific protease （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsSPF-grade 4-month-old APP/PS1 mice were randomly divided into the model group， MCC950 group， and Hei Xiaoyaosan high-， medium-， and low-dose groups. C57BL/6J mice were used as the blank group. After 7 days of adaptive feeding， mice in each group were intervened. The Hei Xiaoyaosan high-， medium-， and low-dose groups were given corresponding doses by gavage （25.79， 12.90， 6.45 g·kg^-1·d^-1）， the MCC950 group was intraperitoneally injected with 10 mg·kg^-1·2 d^-1， and the blank group received the same volume of physiological saline by gavage. After 90 days of intervention， the learning and memory abilities were assessed using the Y maze and Morris water maze tests. The structural changes of hippocampal neurons were observed by hematoxylin-eosin （HE） staining. The expression of amyloid precursor protein （APP） in the hippocampal CA3 region was detected by immunohistochemistry. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin （IL）-10， IL-18， and IL-1β in the hippocampus. Western blot was applied to detect the protein expression of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus. Immunofluorescence was used to detect the co-localization of GSDMD-N and ionized calcium-binding adapter molecule-1 （Iba-1） in the hippocampus. Results① In the Y maze test， compared with the blank group， the spontaneous alternation rate of the model group was significantly reduced （P<0.01）. Compared with the model group， the spontaneous alternation rate in the Hei Xiaoyaosan high- and low-dose groups was significantly increased （P<0.01）. ② In the Morris water maze test， during the 1-4 days of the location navigation test， the escape latency time of mice decreased with the extension of training time. On day 4， compared with the blank group， the model group showed a significantly increased escape latency （P<0.05）. Compared with the model group， the MCC950 group and the Hei Xiaoyaosan low-dose group showed significantly reduced escape latency （P<0.05）. In the spatial exploration experiment， compared with the blank group， the number of platform crossings in the model group was significantly reduced （P<0.01）. Compared with the model group， the Hei Xiaoyaosan low-dose group showed significantly increased platform crossings （P<0.05）. ③ HE staining showed that， compared with the blank group， the hippocampal CA3 cells of the model group were damaged， arranged loosely and irregularly， swollen， with unclear boundaries， and the nuclei were pyknotic and deeply stained. MCC950 and all doses of Hei Xiaoyaosan improved the hippocampal CA3 cell damage in APP/PS1 mice to varying degrees. ④ Immunohistochemical results indicated that， compared with the blank group， the expression of APP in the hippocampal CA3 region was significantly increased in the model group （P<0.01）. MCC950 and all doses of Hei Xiaoyaosan could reduce the expression of APP in the hippocampal CA3 region of APP/PS1 mice （P<0.01）. ⑤ ELISA results showed that the levels of IL-18 and IL-1β in the hippocampus of mice in the model group were significantly increased， and IL-10 levels were significantly reduced （P<0.01）. Compared with the model group， the IL-18 levels in the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were significantly reduced （P<0.01）. IL-1β levels in the hippocampus of the MCC950 group and Hei Xiaoyaosan high-， medium-， and low-dose groups were significantly decreased （P<0.01）. The IL-10 levels in the hippocampus of the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were increased （P<0.05， P<0.01）. ⑥ Western blot results showed that compared with the blank group， the protein levels of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus of the model group were significantly elevated （P<0.01）. Compared with the model group， the content of NLRP3 and Caspase-1 in the hippocampus of the treated groups was decreased （P<0.05， P<0.01）. The content of GSDMD in the hippocampus of the Hei Xiaoyaosan high-， medium-， and low-dose groups was reduced （P<0.05， P<0.01）， and the content of GSDMD-N in the hippocampus of the Hei Xiaoyaosan medium- and low-dose groups was decreased （P<0.05， P<0.01）. ⑦ Immunofluorescence results showed that， compared with the blank group， the co-expression of GSDMD-N and Iba-1 in the hippocampus of the model group was significantly increased （P<0.01）. Compared with the model group， the co-expression of GSDMD-N and Iba-1 in the treated groups was significantly reduced （P<0.01）. ConclusionHei Xiaoyaosan may regulate the NLRP3/Caspase-1/GSDMD signaling pathway to affect the release of inflammatory factors， alleviate neuroinflammation，improve hippocampal histopathological changes，and improve learning and memory deficits，thus providing potential therapeutic benefits for Alzheimer's disease.

The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

The peripheral pulmonary lesions are located far from the central airway and close to the pleura, so it is a challenge for clinical diagnosis of their nature through biopsy. Therefore, the Ion robot-assisted bronchoscopy system which has started its commercialization in China is proposed to diagnose and treat peripheral pulmonary lesions. The Ion system can be used for navigation, registration, biopsy and treatment. In this paper, the structural principle of the Ion system is expounded, and its technical advantages such as shape perception, slender catheter and flexible operation are summarized. It represents the latest development direction of the diagnosis and treatment of peripheral pulmonary lesions. Then, the clinical application and development status of the Ion system are analyzed and discussed in detail. Finally, the development trend of the robot-assisted bronchoscopy system is prospected, which provides new ideas for realizing the "integrated and one-stop" diagnosis and treatment services for peripheral pulmonary lesions based on this system.
Bronchoscopy/instrumentation* ; Humans ; Robotics ; Robotic Surgical Procedures

Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective To investigate the relationship between the expression level of miRNA Let-7 and the deletion of DNA mismatch repair(dMMR)proteins in endometrial carcinoma(EC).Methods A total of 74 patients with EC who underwent radical surgery at Lianyungang Maternal and Child Health Hospital in Jiangsu Province from May 2016 to December 2022 were selected.Immunohistochemistry was used to detect the expression of dMMR proteins(including MLH1,PMS2,MSH2,and MSH6),while real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was performed to measure the relative expression levelof miRNA Let-7.According to the expression of dMMR proteins,EC patients were divided into the complete expression group(n=43)and the absent expression group(n=31).Logistic multivariate regression analysis was conducted to identify risk factors associated with dMMR protein deficiency,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of relevant factors.Results In 74 cases of EC,the expression level of miRNA Let-7 was higher in the myographic infiltration＜1/2 group than in the myographic infiltration ≥ 1/2 group,and the difference was significant(t=1.79,P=0.04).The deletion rate of dMMR protein expression was 41.89％,the deletion rate in patients aged＜55 years and miRNA Let-7 low expression group(＜0.715)were higher than those in ≥ 55 years and miRNA Let-7 high expression group(≥ 0.715),with significant differences(x2=3.92,4.50,all P＜0.05).Logistic regression analysis revealed that miRNA Let-7 expression level was an independent risk factor for dMMR expression deletion(P=0.012).Spearman correlation analysis demonstrated a negative correlation between miRNA Let-7 expression level and dMMR protein deletion(r=-0.247,P=0.034).ROC curve analysis indicated that the expression level of miRNA Let-7 had a certain predictive value for dMMR protein deletion in EC patients,with an AUC of 0.737,an optimal critical value of 0.77,a sensitivity and a specificity of 0.651 and 0.806,respectively.Conclusion The expression level of miRNA Let-7 was correlated with the deletion of dMMR proteins in patients diagnosed with EC.Moreover,it served as a potential risk factor for dMMR protein deficiency.It may offer valuable insights into predicting dMMR expression deletion.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective:To study the protective effects and mechanism of Melastoma sanguineum Sims fruit extract (MSE) on chronic chemical liver injury induced by ethanol, acetaminophen and carbon tetrachloride in mice; To discuss it mechanism.Methods:Totally 96 mice were divided into normal control group, ethanol model group, ethanol+bifendate control group and ethanol+MSE high-, medium- and low-dosage groups, APAP model group, APAP+bifendate control group and APAP+MSE high-, medium- and low-dosage groups, CCl 4 model group, CCl 4+bifendate control group and CCl 4+MSE high-, medium- and low-dosage groups, with 6 mice in each group. Except for the normal control group, the other groups were respectively prepared for the ethanol model, the APAP model and the CCl 4 model. The mice in the MSE high-, medium- and low-dosage groups were intragastrically administrated with 10, 5 and 2.5 g/kg of MSE, respectively; the bifendate control group was intraperitoneally injected with 15 mg/ml bifendate solution at 75 mg/kg; the normal control group was intraperitoneally injected with equal volume of normal saline/peanut oil solution once a day for 25 consecutive days. The levels of GPT, GOT and total bilirubin (TBIL) in serum were detected; the activities of SOD and GSH-Px and the content of MDA in liver tissue were detected; the mRNA expressions of TNF-α, IL-6, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were detected by qRT-PCR; the protein expressions of cytochrome P450 CYP1A1, CYP1A2, and CYP3A in liver tissue were detected by Western blot; the pathological changes of the liver tissue were observed by HE staining. Results:Compared with the corresponding ethanol, APAP and CCl 4 model groups, the serum GPT, GOT and TBIL levels of mice in the ethanol+bifendate control group and ethanol+MSE high- and medium-dosage groups, the APAP+bifendate control group and APAP+MSE high- and medium-dosage groups, and the CCl 4+bifendate control group and CCl 4+MSE high- and medium-dosage groups decreased ( P<0.01 or P<0.05), the activities of SOD and GSH-Px in the liver tissue increased ( P<0.01 or P<0.05), and the MDA level decreased ( P<0.01 or P<0.05), and the mRNA levels of IL-6 and TNF-α decreased ( P<0.01); the mRNA levels of ADH and ALDH in the ethanol+MSE high-, medium-, and low-dosage groups decreased ( P<0.01). Compared with the APAP model group, the expressions of CYP1A1 and CYP1A2 in the APAP+MSE groups increased ( P<0.01), and the expression of CYP3A protein decreased ( P<0.05); compared with the CCl 4 model group, the expressions of CYP1A1, CYP1A2 and CYP3A proteins in the CCl 4+MSE groups decreased ( P<0.05). Conclusion:MSE has a protective effect on chronic chemically-induced liver injury induced by ethanol, APAP, and CCl 4 in mice, and its mechanism may be related to antioxidant stress, inhibition of inflammatory response, and regulation of the expression of cytochrome P450-related enzymes.