Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Alzheimer's disease(AD),a common geriatric ailment,exerts a severe impact on people's lives.Traditional Chinese medicine(TCM)demonstrates a favorable effect on the intervention of AD,while the mechanism remains in the exploratory phase.Recent studies have indicated that astrocytes play a significant role in AD.The mechanism of TCM in the treatment of AD from the perspective of astrocyte regulation was explored,and the roles of astrocytes in the pathogenesis of AD was summarized,namely maintaining energy metabolism,regulating synaptic plasticity,and mediating inflammatory responses,thereby providing a TCM-based solution with a clear mechanism for clinical and scientific intervention in AD.

Alzheimer's disease(AD),a common geriatric ailment,exerts a severe impact on people's lives.Traditional Chinese medicine(TCM)demonstrates a favorable effect on the intervention of AD,while the mechanism remains in the exploratory phase.Recent studies have indicated that astrocytes play a significant role in AD.The mechanism of TCM in the treatment of AD from the perspective of astrocyte regulation was explored,and the roles of astrocytes in the pathogenesis of AD was summarized,namely maintaining energy metabolism,regulating synaptic plasticity,and mediating inflammatory responses,thereby providing a TCM-based solution with a clear mechanism for clinical and scientific intervention in AD.

Myelodysplastic syndrome (MDS) is a malignant hematologic tumor, which is currently difficult to cure. The theory of Xuanfu was proposed by Liu Wansu, which is unique in the clinical evidence of Chinese medicine and is less frequently applied to hematological diseases. The application of Xuanfu theory in myelodysplastic syndrome provides new ideas for the treatment of the disease. The abnormal flow of Qi, blood and fluids caused by the occlusion of the Xuanfu is the cause of toxic stasis obstruction, which is the pathogenesis of toxic stasis obstruction. Thus, the method of dispersion of Bone from Xuanfu, the external treatment of Xuanfu, and regulation of liver qi and Xuanfu help to return to normal of opening and closing function of Xuanfu, and release toxic stasis. In this paper, we analyzed the evidence of toxin-stasis obstruction in myelodysplastic syndrome from the theory of Xuanfu, aiming to provide a feasible theoretical basis for clinical treatment of the disease.

Objective To construct and identify a patient-derived organoid model,and to investigate the sensitivity of chemotherapy drugs using this model.Methods Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion,and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture.Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved.The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations;Cell Titer-Glo?3D reagent was used to measure cell viability,and the results of drug sensitivity were analyzed.Results Two patient-derived pancreatic cancer organoids were successfully constructed,and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient.Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil,and patient 1 was more sensitive than patient 2.There were individual differences in the response to drugs between the organoids from different patients.Conclusion The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test,which is expected to provide a reference for clinical medication.

Transthyretin(TTR) protein is a tetramer protein, synthesized mainly by the liver. TTR can be misfolded and deposited as amyloid fibrilae and deposited in the myocardial interstroma leading to transthyroxin amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM was included in China's First List of Rare Diseases. Therapeutic strategies for ATTR-CM include blocking TTR synthesis in the liver, stabilizing TTR tetramers and destroying TTR fibra. Small molecule drugs such as tafamidis and diflunisal offer new treatment options for patients. Chlorobenzolic acid became the first drug approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. Small interfering RNA(siRNA)patisiran and antisense oligonucleotide (ASO)inotersen block TTR expression in the liver and have been approved for the treatment of ATTR variant polyneuropathy (ATTRv-PN)and are in phase Ⅲ trials for the treatment of ATTR-CM. Other siRNA drugs, vutrisiran, and ASO, eplontersen, are being evaluated for clinical efficacy. This article reviews the development of RNA-targeted therapeutics and gene-editing drugs using CRISPR-Cas9.

Remote pharmaceutical care refers to the process that pharmacists provide pharmaceutical care to patients remotely through information technology. Remote pharmaceutical care in China starts late and develops slowly. Therefore ，this paper discusses the pharmaceutical care modes that pharmacists at home and abroad can provide under the remote mode by collecting literature. The results show that foreign remote pharmaceutical care starts early and is relatively mature. The service mainly included remote follow-up and intervention ，24-hour online prescription and order review ，24-hour online drug reorganization ，and guidance on rational drug use in remote areas or community hospitals. The service population covers patients with cardiovascular disease ， diabetes，asthma，AIDS and so on. Some hospitals have established an integrated pharmaceutical care system of “Internet+Medical Consortium”in China ，with which pharmacists can provide patients with pharmaceutical care such as remote follow-up and intervention，drug consultation and so on. With the promotion of telemedicine ，domestic pharmacists can gradually expand the scope of services ，expand pharmaceutical services such as remote consultation and remote popular science push ，and realize the sharing of high-quality pharmaceutical care for the whole people.

We aim to screen out the active components that may have therapeutic effect on coronavirus disease 2019 (COVID-19) from the severe and critical cases' prescriptions in the "Coronavirus Disease 2019 Diagnosis and Treatment Plan (Trial Ninth Edition)" issued by the National Health Commission of the People's Republic of China and explain its mechanism through the interactions with proteins. The ETCM database and SwissADME database were used to screen the active components contained in 25 traditional Chinese medicines in 3 prescriptions, and the PDB database was used to obtain the crystal structures of 4 proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular docking was performed using Autodock Vina and molecular dynamics simulations were performed using GROMACS. Binding energy results showed that 44 active ingredients including xambioona, gancaonin L, cynaroside, and baicalin showed good binding affinity with multiple targets of SARS-CoV-2, while molecular dynamics simulations analysis showed that xambioona bound more tightly to the nucleocapsid protein of SARS-CoV-2 and exerted a potent inhibitory effect. Modern technical methods are used to study the active components of traditional Chinese medicine and show that xambioona is an effective inhibitor of SARS-CoV-2 nucleocapsid protein, which provides a theoretical basis for the development of new anti-SARS-CoV-2 drugs and their treatment methods.
Humans ; SARS-CoV-2 ; Molecular Docking Simulation ; Medicine, Chinese Traditional ; Molecular Dynamics Simulation ; Nucleocapsid Proteins ; Antiviral Agents/pharmacology* ; COVID-19 Drug Treatment

Off-label drug use is a global problem in clinical practice. The management status, attitude and medical insurance coverage of off-label drug use are different in various countries. By analyzing the management and reimbursement policy of off-label drug use in other countries, the authors suggested that China should speed up the institutional arrangements of off-label drug use and establish relevant management systems, and strengthen the supervision of off-label drug use, so as to guarantee the rights of patients to the best treatment.