The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

Paraneoplastic neurologic syndromes （PNS） are immune-mediated disorders of the nervous system triggered by cross-immune response induced by tumor-associated antigens. Since high-risk paraneoplastic antibodies are highy associated with malignancies， they have an important clinical value in the early recognition， tumor screening， and prognostic assessment of PNS. The diagnostic criteria updated in 2021 further refined the classification of high-risk antibodies and clarified their value in risk assessment. This article systematically reviews the clinical spectrum， tumor associations， and immunopathogenic mechanisms of neurological disorders associated with the high-risk paraneoplastic antibodies such as anti-Hu， anti-Ri， anti-CV2， anti-Ma2， anti-amphiphysin， anti-Yo， anti-PCA2， anti-Tr， anti-SOX1， and anti-KLHL11 antibodies. Immunotherapy combined with active control of primary tumor is the main treatment strategy for such disease， but with a limited overall therapeutic effect， and early identification is of particular importance. In the era of the wide application of immune checkpoint inhibitors （ICIs）， the risk of ICIs in inducing or exacerbating should be taken seriously in clinical practice. Mechanistic research， multimodal diagnostic approaches， and individualized treatment strategies should be enhanced in the future to improve the prognosis of patients.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective To investigate the relationship between the changes in P(cv-a)CO?/C(a-cv)O? ratio and hypoxic states in patients with hemorrhagic shock after effective fluid resuscitation.Methods Thirty hemorrhagic shock patients who were admitted to ICU Dongguan Eighth People's Hospital from October 1,2021 to November 30,2023 were selected as research objects.All the patients underwent early fluid resuscitation.Arterial and central venous blood gas analysis was performed,and arterial lactate concentration was measured before resuscitation,and at 2 h,6 h,12 h,and 24 h after resuscitation.The P(cv-a)CO2/C(a-cv)O2,the gradient of P(cv-a)CO2/C(a-cv)O2,and lactate clearance rate were calculated.Results There was a positive correlation between the P(cv-a)CO?/C(a-cv)O? ratio and lactate concentration,as well as between the gradient of P(cv-a)CO?/C(a-cv)O? and lactate clearance rate at each time point(P<0.05).There were significant differences in the P(cv-a)CO?/C(a-cv)O?,gradient of P(cv-a)CO?/C(a-cv)O?,and lactate clearance rate after resuscitation among patients with different prognoses(P<0.05).Conclusion The P(cv-a)CO2/C(a-cv)O2 and its change rate,as well as lactate clearance rate,can predict the prognosis of patients with hemorrhagic shock.

Nonconvulsive status epilepticus （NCSE） is a state of persistent epileptic seizure characterized by disturbance of consciousness or major neurological deficits， without obvious limb convulsions. Due to a lack of obvious clinical manifestations and the potential risk of neurological damage， current research focuses on rapid identification， accurate classification， and optimization of treatment strategies. Since there is a lack of obvious motor symptoms in NCSE， it is difficult for clinicians to quickly identify the disease through traditional signs， which poses great challenges to diagnosis， and underdiagnosis may lead to delayed treatment and poor prognosis. This article systematically reviews the epidemiological characteristics， clinical manifestations， and key diagnostic points of NCSE and discusses existing treatment regimens and prognosis， in order to provide a reference for clinical practice.
Diagnosis

OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance (IR) in type 2 diabetes mellitus (T2DM) rats.METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet.The rats were randomly divided into normal control group,model group,Qingxue xiaozhi jiangtang formula low-dose and high-dose groups (6.525,13.05 g/kg,calculated by raw material) and metformin group (positive control,0.18 g/kg),with 8 rats in each group.Administration groups were given relevant medicine intragastrically;normal control group and model group were given constant volume of normal saline intragastrically,once a day,for consecutive 6 weeks.Body mass and fasting blood glucose (FBG) were determined,and oral glucose tolerance test was conducted.Serum fasting insulin (FINS) level was measured to calculate the insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI).Additionally,the level of serum lipids,liver function,oxidative stress indicators and inflammatory factors were assessed.The phosphorylation levels of kinase R-like endoplasmic reticulum kinase (PERK) and forkhead box O1 (FOXO1) protein in liver tissue of rats were determined.RESULTS Compared with model group,the body weight,ISI,the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group (P<0.05);FBG,blood glucose level at 120 minutes of glucose loading,area under the curve of glucose,FINS,HOMA-IR,low-density lipoprotein cholesterol,total cholesterol,triglyceride,alanine transaminase,aspartate transaminase,alkaline phosphatase,malondialdehyde,interleukin-6,tumor necrosis factor-α,and C-reactive protein levels were significantly reduced (P<0.05);the pathological damage of liver tissue had significantly improved,and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased (P<0.05).CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism,inflammation factor and oxidative stress levels,and alleviate insulin resistance in T2DM rats.Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

ObjectiveTaking the oligosaccharides in Rehmanniae Radix（RR） as the research object， the content determination method based on high performance liquid chromatography-evaporative light scattering detection（HPLC-ELSD） and thin layer chromatography（TLC） identification method were established to explore the content and distribution of oligosaccharides in different RR herbs and decoction pieces. MethodA total of 10 batches of fresh and raw RR， 12 batches of RR decoction pieces and Rehmanniae Radix Praeparata（RRP） were collected. A TLC identification method for fructose， sucrose， manninotriose， raffinose and stachyose in RR was established by using silica gel G thin-layer plates with ethyl acetate-water-anhydrous formic acid-glacial acetic acid（12∶6∶5∶4） as the developing agent and 10% sulfuric acid-ethanol solution as chromogenic agent. A HPLC-ELSD was used to determine the contents of fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose in different RR herbs and decoction pieces. Then principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to analyze the contents of 7 kinds of saccharides in RR herbs and decoction pieces， and the differential components were screened with the value of variable importance in the projection（VIP）>1. ResultThe results of TLC identification showed that fresh RR， raw RR and its decoction pieces showed spots of the same color on the corresponding positions with the control products of stachyose， raffinose and sucrose， while the TLC of RRP showed spots of the same color at corresponding positions to manninotriose and fructose controls. The results of methodological investigations of 7 analytes met the requirements of determination. Only glucose， sucrose， raffinose and stachyose were detected in 10 batches of fresh RR and 10 batches of raw RR herbs， the average contents of which were 0.84%， 4.62%， 2.42% and 57.90% in fresh samples， while those were 3.16%， 9.36%， 7.05% and 38.10% in raw samples， respectively. In 12 batches of RR decoction pieces， the contents of the above seven sugars（fructose， glucose， sucrose， melibiose， raffinose， manninotriose and stachyose） were 1.68%， 4.27%， 9.96%， 0.53%， 6.85%， 3.05% and 37.52%， respectively. In 12 batches of RRP， the contents of the above seven sugars were 10.62%， 11.01%， 1.25%， 3.35%， 1.12%， 28.16% and 6.39%， respectively. The results of multivariate statistical analysis showed that fresh RR， raw RR and RRP could be distinguished from each other by the contents of the 7 sugars， and the main differential components were stachyose， sucrose， raffinose and manninotriose. ConclusionIn terms of oligosaccharides， the contents and types of saccharides in different herbs and decoction pieces of RR are quite different， and the TLC identification method based on this can be used to distinguish raw RR from RRP， which can lay a foundation for improving the quality standard of RR and developing and applying oligosaccharides in different processed products of RR.

Objective:To investigate mevalonic acid(MEV)on reversing the antitumor effects of fluvastatin sodium(FS)on tongue squamous cell carcinoma(TSCC)cells.Methods:TSCC HSC-4 cells were treated with different concentrations of FS and MEV re-spectively or in combination.Cell counting kit-8,flow cytometry,wound healing,immunofluorescence and western blotting assays were conducted to examine cell proliferation,apoptosis and migration capacities,as well as the expression levels of Ras homolog family member A(RHOA),tissue factor(TF)and B-cell lymphoma-2-associated X(BAX)proteins,respectively.Results:FS inhibited HSC-4 cell proliferation and migration,decreased the expression of RHOA and TF,and increased BAX expression.MEV reversed the above antitumor effects of FS and promoted intracellular RHOA and TF expression.Conclusion:MEV reverses the antitumor effects of FS on HSC-4 cells in vitro.

Objective To analysis the effectiveness and cost of Internet-based anticoagulation clinic versus traditional anticoagulation clinic treatment at Nanjing Drum Tower Hospital during the COVID-19 pandemic.Methods We reviewed and analyzed the clinical data of patients receiving anticoagulation management through Internet-based outpatient care and traditional outpatient care in Nanjing Drum Tower Hospital,from June 1,2020 to June 30,2021.Variability in time in therapeutic range(TTR)and international normalized ratio(INR)were calculated for enrolled patients.Patients meeting TTR≥60%and INR variability<0.65 were considered optimal anticoagulation quality.Cost-effectiveness analysis was conducted from the patients'perspective,with results expressed using the incremental cost-effectiveness ratio(ICER).Results In the"Internet-based anticoagulation outpatient care"and"traditional face-to-face anticoagulation outpatient care"groups,19 individuals(67.86%)and 67 individuals(76.14%)met the criteria for optimal anticoagulation quality,respectively.The mean TTR was(71.83±19.17)%in the Internet-based group and(71.74±23.41)%in the traditional face-to-face group,indicating similar levels of warfarin anticoagulation quality between the two groups.The ICER was calculated as 327.17 yuan,less than the per capita gross domestic product(GDP)of 2021.Conclusion During the COVID-19 pandemic,Nanjing Drum Tower Hospital's Internet-based anticoagulation outpatient care effectively complemented the government's epidemic control policies.It ensured equivalent anticoagulation outcomes and significantly reduced patients'financial burdens.This approach offers new insights and guidance for optimizing healthcare services in the post-pandemic era.