OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

OBJECTIVE To improve the diagnosis and treatment level of critically ill infectious diseases， standardize the clinical application of nanopore sequencing and promote the sound development of the technology. METHODS Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society and Expert Committee of Precision Medicine for Clinical Treatment of Guangdong Pharmaceutical Association initiated and organized multidisciplinary experts to discuss and determine the consensus writing outline by using the nominal group method， forming a preliminary consensus draft； expert consultation was performed by using Delphi method， and then experts’ opinions were analyzed and revised to form consensus. RESULTS & CONCLUSIONS Consensuses of Experts on the Application of Nanopore Sequencing Technology in the Detection of Pathogenic Microorganisms covers targeted sequencing， metagenomic sequencing and whole genome sequencing， and is standardized in terms of sample collection and storage， detection process， bioinformatics analysis and report interpretation； the recommendations are provided for the key issues.

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

Objective To investigate the related factors of early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels. Methods Clinical materials of 480 elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels were retrospectively analyzed. The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function of patients within 72 hours after thrombectomy, and the patients were divided into deterioration group and non-deterioration group. The baseline materials were compared between the two groups, the factors of early neurological deterioration were analyzed, and the receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of risk. Results Among 480 elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels, 92 cases (19.17%) had early neurological deterioration; the blood glucose level, white blood cell count, incidence of dysphagia, and incidence of coma in the deterioration group were significantly higher than those in the non-deterioration group (P < 0.05); the Logistic regression analysis showed that high level of blood glucose (95%CI, 1.203 to 1.478), high level of white blood cell count (95%CI, 1.159 to 1.408), dysphagia (95%CI, 7.049 to 31.475), and coma (95%CI, 8.375 to 43.195) were risk factors for early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels (OR>1, P < 0.05). ROC curve results showed that blood glucose, white blood cell count, dysphagia, and coma had certain predictive value for early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels[the area under the curve (AUC) was 0.733, 0.708, 0.707 and 0.701]; the ROC curve showed AUC was 0.934, indicating that the model was reliable and stable. Conclusion Early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels may be related to factors such as blood glucose, white blood cell count, dysphagia, and coma. Early risk assessment and relevant intervention measures can be taken clinically to improve prognosis.

Background::Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low) or high levels (CD8 high) on HIV-1 replication inhibition after HIV-1 invasion into individual. Methods::Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 +CD8 low T cells and their counterpart CD3 +CD8 high T cells at different stages of HIV-1 infection. Results::Compared with healthy donors, CD3 +CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 +CD8 low T cells gradually decreased. Simultaneously, CD3 +CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 +CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 -HLA-DR +CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 +CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 +CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 +CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 +CD8 low T cells, but comparable amounts of CD3 +CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 +CD8 low T cells than CD3 +CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Conclusions::Our findings suggest that CD3 +CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 +CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 +CD8 high T cells.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Objective To evaluate predictive factors affecting the short-term efficacy of PD-1 inhibitors in non-small cell lung cancer (NSCLC) and to construct a prediction model. Methods From October 2019 to November 2021, 221 patients with advanced NSCLC who met the inclusion criteria and were treated with PD-1 inhibitors were prospectively enrolled. Patients who were enrolled before May 1st, 2021 were included inthe modeling group (n=149), whereas those who enrolled thereafter were included in the validation group (n=72). The general clinical data of patients, information of the four TCM diagnoses were collected, and TCM syndrome elements were identified. R software version 4.0.4 was used in constructing a nomogram clinical prediction model of objective response rate. The predictive ability and discrimination of the model were evaluated and externally validated by using a validation group. Results After two to four cycles of PD-1 inhibitor therapy in 221 patients, the overall objective response rate was 44.80%. Multivariate logistic regression analysis of the modeling group showed that the TPS score (OR=0.261, P=0.001), number of treatment lines (OR=3.749, P=0.002), treatment mode (OR=2.796, P=0.019), qi deficiency disease syndrome elements (OR=2.296, P=0.043), and syndrome elements of yin deficiency disease (OR=3.228, P=0.005) were the independent predictors of the short-term efficacy of PD-1 inhibitors. Based on the above five independent predictors, a nomogram prediction model for the short-term efficacy of PD-1 inhibitors was constructed. The AUC values of the modeling and validation groups were 0.8317 and 0.7535, respectively. The calibration curves of the two groups showed good agreement between the predicted and true values. The mean absolute errors were 0.053 and 0.039, indicating that the model has good predictive performance. Conclusion The nomogram model constructed on the basis of the syndrome elements of Qi-deficiency disease and Yin-deficiency syndrome of TCM, as well as TPS score, number of treatment lines and treatment mode, is a stable and effective tool for predicting the short-term efficacy of PD-1 inhibitors in advanced non-small cell lung cancer.

OBJECTIVE To optimize the extraction process of polysaccharides from Dendrobium officinale， and preliminarily study its effect on acute lung injury （ALI） in mice. METHODS Using D. officinale as raw material， the polysaccharides were extracted from D. officinale by ultrasonic-assisted hot water immersion. Using the extraction rate of D. officinale polysaccharides as response value， the single-factor experiments and Box-Behnken response surface method were used to optimize the ratio of material to liquid， extraction time and extraction temperature. ALI mice were induced by lipopolysaccharide. Using prednisone acetate （5 mg/kg） as the positive control， the effects on the mass ratio of wet and dry lung and pathological changes of lung tissue （HE staining and Masson staining） of low-dose， medium-dose and high-dose D. officinale polysaccharides （50，100，200 mg/kg） were investigated. RESULTS The optimal extraction technology of D. officinale polysaccharides was as follows： the ratio of material to liquid was 1∶25 （g/mL）， the extracting time was 1 h， and the extracting temperature was 58 ℃ . Under these conditions， the average extraction rate of D. officinale polysaccharides was 37.75% （RSD＝1.12%，n＝3）， the relative error of which with predicted value （38.63%） was 2.28%. Compared with the model group， the ratios of wet and dry lung in the positive control group and D. officinale polysaccharides groups were all decreased significantly （P＜0.05 or P＜0.01）， and the pathological changes in lung tissue （severe destruction of alveolar structure， significant widening of alveolar septa， extensive infiltration of inflammatory cells and proliferation of fibroblasts） were alleviated to varying degrees. CONCLUSIONS The optimal extraction process of D. officinale polysaccharides is feasible； the obtained polysaccharide extract has a certain improvement effect on ALI in mice.

Animal experiments play an important role in the process of biomedical research, and is a necessary way to transform basic medicine into clinical medicine. The standardization of animal experimental studies and reports determines the reliability and reproducibility of research results, and is also the key to transforming the results of animal experiments into clinical trials. In view of how to design and implement animal experiments, write animal experiment reports, and publish relevant academic papers in a more standardized way, LACM (Laboratory Animal and Comparative Medicine) has launched a new column of comparative medical research and reporting standards from 2023, focusing on the introduction and interpretation of international general norms related to laboratory animal and comparative medicine, such as ARRIVE 2.0 guidelines (Animal Research: Reporting of In Vivo Experiments). This article focuses on the development and application, basic content and priority of ARRIVE 2.0, as well as the scheme of implementing ARRIVE 2.0 guidelines in international biomedical journals, and explains the current situation and future plans of LACM following ARRIVE 2.0 guidelines. The research and report of animal experimental medicine following the ARRIVE 2.0 guidelines and other international norms is one of the important driving forces to promote the high-quality development of experimental animal science and biomedicine in China, and also a powerful means to implement the 3R principle and improve the welfare of laboratory animals. Through this article, we hope the majority of scientific researchers and editors will attach great importance and actively implement these international standards.