To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

Objective To explore the expression of triggering receptor expressed on myeloid cells 2(TREM2)in high-glucose microglia and to investigate the role of TREM2 in the proliferation,migration and phagocytosis of high-glucose microglia.Methods Microglia cells were divided into control group and high-glucose treatment group(67.5 mmol/L glucose,24 h).The microglia cells were counted and the expression of Iba1 and TREM2 was de-tected.TREM2 siRNA was transfected to detect the proliferation and migration of microglia.The amyloid β-peptide(Aβ)with a fluorescent tag was added to observe the phagocytosis of Aβ by microglia.Results Compared to normal microglia,the number of microglia significantly decreased after high-glucose treatment(P＜0.001),while the ex-pression of TREM2 and Iba1 markedly increased(P＜0.001).High glucose and TREM2 did not affect the prolifer-ation of microglia.Compared to the normal group,the migration of microglia significantly decreased after high-glu-cose treatment(P＜0.05)and TREM2 did not affect the migration ability of high-glucose microglia.Compared to the normal group,the phagocytosis of Aβ by microglia significantly decreased in the high-glucose treated group(P＜0.001).Furthermore,TREM2 knockdown further decreased the phagocytosis of Aβ by high-glucose microglia(P＜0.001).Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treat-ment,which significantly affects phagocytosis of Aβ by microglia.

Objective To investigate the predictive value of preoperative blood inflammatory markers for the recurrence risk in patients with basal cell carcinoma(BCC).Methods A total of 225 patients with BCC were divided into the high-risk recurrence group(155 cases)and the low-risk recurrence group(70 cases).General information and preoperative hematological indicators were collected in the two groups of patients.The neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),systemic inflammation marker(SIM)and platelet-to-lymphocyte ratio(PLR)were calculated.Receiver operating characteristic(ROC)curves were used to determine the predictive value of hematological markers with statistically significant differences between the two groups for BCC recurrence and to establish optimal cutoff values.Univariate and multivariate Logistic regression analyses were conducted to identify factors influencing BCC recurrence.A multivariate Logistic regression model was established to predict the recurrence risk of BCC.Area under the curve(AUC)and the Hosmer-Lemeshow test were used to evaluate the prediction efficiency and goodness-of-fit of the model.Results ROC analysis identified that optimal cutoff values for LMR and SIM were 5.12 and 0.86,respectively.Univariate Logistic regression analysis showed that LMR,SIM,ulceration at the primary tumor site,UV exposure and tumor maximum diameter were factors influencing BCC recurrence.Multivariate Logistic regression revealed that SIM≥0.86,tumor maximum diameter≥2.0 cm and UV exposure were risk factors for BCC recurrence,while LMR≥5.12 had a protective effect.The Logistic prediction model for BCC recurrence risk was Logit(P)=-1.598-1.517×LMR+1.323×SIM+2.406×UV exposure+3.465×tumor maximum diameter,with good model fit(P=0.725)and an AUC of 0.869(95%CI:0.822-0.917)for predicting BCC recurrence risk.Conclusion Monitoring preoperative LMR and SIM levels can assist in assessing the risk of recurrence in BCC patients and provide important guidance for clinical decision-making.

Objective:To evaluate the safety and efficacy of 225Ac-prostate specific membrane antigen (PSMA) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Methods:Eleven patients (age (70.0±8.8) years) with mCRPC who were treated with 225Ac-PSMA-617 between July 2021 and October 2023 in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. In order to assess efficacy, the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria were used to evaluate the changes in prostate specific antigen (PSA) level after the treatment. 68Ga-PSMA-11 PET/CT imaging was performed at the baseline and after the treatment, and molecular imaging response was assessed using the modified PET response criteria in solid tumors (PERCIST) 1.0. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Toxicity was assessed by common terminology criteria for adverse events version 5.0 (CTCAE 5.0). The paired t test or Wilcoxon signed rank test was used to compare the parameters before and after treatment. Results:Post-treatment PSA levels were significantly lower than pre-treatment in 9 of 11 patients (17.83(4.74, 41.25) vs 124.33(77.85, 784.22) μg/L; z=-2.67, P=0.008), and 6 of them decreasing by more than 50% and 2 patients experienced progressive disease (PD) with PSA levels rising by more than 25%. Post-treatment 68Ga-PSMA-11 PET/CT showed that 7 patients achieved partial response (PR), 2 patients achieved stable disease (SD), and 2 patients were with PD. The OS was 12.0(10.0, 18.0) months and PFS was 8.0(6.0, 11.0) months in 11 patients. There were no statistically significant differences after therapy in WBC counts, Hb, PLT, creatinine, glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, total bilirubin ( z values: from -1.07 to 0.00, t values: from -0.77 to 1.76, all P>0.05). No grade Ⅲ/Ⅳ nephrotoxicity or salivary gland toxicity was observed. Conclusion:225Ac-PSMA-617 is a promising novel therapeutic option for mCRPC with favorable safety and tolerability.

Systemic lupus erythematosus(SLE)is an autoimmune disease with high heterogeneity in tissues and organs,Whose pathogenesis is still unclear.Lymphocytes are important immune cells involved in the occurrence and development of SLE.It has been found that the abnormal activation of T cells and B cells are important causes of SLE.In this review,by summarizing the role of T cells and B cells in the pathogenesis of SLE and the latest research progress in lymphocyte-targeted treatment strategy of SLE,the important scientific evidences can be provided to the study of the pathogenesis of SLE and the development of new medicines for the treatment of SLE.

Lung cancer is a major cause of cancer-related mortality worldwide. Among patients with non-small cell lung cancer (NSCLC), approximately 3%-7% harbor anaplastic lymphoma kinase (ALK) gene fusions. In recent years, multiple tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with metastatic ALK-positive NSCLC. However, disease progression due to resistance remains a challenge. This article retrospectively analyzes a case of advanced lung adenocarcinoma with the echinoderm microtubule associated protein like 4 (EML4)-ALK fusion variant 3 (V3). The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/genetics* ; Aminopyridines/therapeutic use* ; Crizotinib/therapeutic use* ; Drug Resistance, Neoplasm/drug effects* ; Lactams/therapeutic use* ; Lung Neoplasms/genetics* ; Oncogene Proteins, Fusion/metabolism* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/metabolism* ; Pyrazoles/therapeutic use*

OBJECTIVE: To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations. METHODS: A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3). CONCLUSION The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.
Humans ; Child ; Male ; Computational Biology ; Diarrhea ; Gene Frequency ; Inflammatory Bowel Diseases/genetics* ; Mutation

Migraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients' metabolites/proteins may precede that of the brain.
Humans ; Migraine Disorders/etiology* ; Brain/diagnostic imaging* ; Acupuncture Therapy/methods* ; Magnetic Resonance Imaging

Objective:To investigate and analyze the status quo of death cognition and hospice care attitude of clinical medical graduate students, to compare the differences between the two groups, and to explore the correlation between death cognition and hospice care attitude, so as to provide the reference for the reform and construction of death cognition and hospice care education in medical colleges and universities in China.Methods:A survey was carried out on 496 doctoral and postgraduate students majoring in clinical medicine by using the "Questionnaire of General Sociology Survey", the Chinese version of the "Death Attitude Profile Revised Scale", and the Chinese version of the "Frommelt Attitudes Toward Care of the Dying Scale Form B (FATCOD-B)" to investigate the death cognition and hospice care attitude of 496 doctoral and postgraduate students majoring in clinical medicine, and classified and compared the survey results of the two groups. The results of this study were statistically analyzed by t-test, Pearson correlation analysis and other statistical methods. Results:A total of 469 valid questionnaires were recovered after excluding 27 unqualified questionnaires. Statistical analysis showed that the scores of each dimension in the death attitude description scale of doctoral students were ranked as follows: approach acceptance (4.28±0.53), neutral acceptance (3.99±0.41), death avoidance (2.74±0.63), fear of death (2.65±0.57) and escape acceptance (2.47±0.69) the scores of postgraduates were ranked as neutral acceptance (3.96±0.52), approach acceptance (2.84±0.61), fear of death (2.78±0.65), death escape (2.62±0.73), escape acceptance (2.39±0.77). At the same time, the scores of hospice care attitude in the doctoral group were higher than those in the master group [(110.63±8.96) vs. (106.78±6.52)], and the difference was statistically significant ( P<0.001). In addition, the scores of "fear of death" and the scores of hospice care attitudes were negatively correlated with the scores of doctoral and master students ( r=-0.25, r=-0.21), while the scores of hospice care attitudes were positively correlated with the scores of "neutral acceptance" in death cognition ( r=0.50, r=0.32). However, the hospice care attitude scores of doctoral students were negatively correlated with the "death avoidance" scores in death cognition ( r=-0.27). Conclusion:Doctoral and postgraduate students have a certain awareness of hospice care, while their death cognition and hospice care attitude still need to be improved and strengthened from sociology, psychology, ethics and other perspectives. The above will promote the harmony between doctors and patients while meeting the needs of an aging society in China.