Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L^-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L^-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.

Background Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides that have been used in various pest management regimens worldwide as alternatives to conventional insecticides. Recently, several studies have indicated that humans are widely exposed to NEOs, but limited is known about the levels and associated health risks of NEOs exposure among children. Objective To estimate exposure levels of four kinds of NEOs in urine samples among 5-year-old children from Laizhou Wan, Shandong Province, and to evaluate health risks of single and cumulative exposure to NEOs among children in this area. Methods A total of 205 children who participated in the 5-year-old follow-up in Laizhou Wan Birth Cohort (LWBC) were included. Urinary concentrations of four NEOs [imidacloprid (IMI), acetamiprid (ACE), clothianidin (CLO), and thiamethoxam (THM)] were measured by high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Based on the detected NEOs concentrations, estimated daily intake (EDI) was calculated, and the health risk of exposure to single NEO was assessed using hazard quotient (HQ, risk threshold=1). A relative potency factor (RPF) approach was used to standardize the concentrations of the four NEOs by IMI to calculate their cumulative concentrations. Then, the health risk of cumulative exposure to the four NEOs was further evaluated based on the HQ method. Results The detection rates of the four NEOs in the 5-year-old children were all above 90%, and their median creatinine-adjusted urinary concentrations were in the order from high to low as follows: CLO (1.373 μg·g⁻¹) > THM (0.628 μg·g⁻¹) > IMI (0.310 μg·g⁻¹) > ACE (0.073 μg·g⁻¹). Of the four NEOs, the median EDI of IMI was 0.035 µg·kg⁻¹·d⁻¹, higher than those of CLO (0.032 µg·kg⁻¹·d⁻¹), THM (0.012 µg·kg⁻¹·d⁻¹), and ACE (0.002 µg·kg⁻¹·d⁻¹). The maximum HQ values of IMI, CLO, THM, and ACE were 0.168, 0.152, 0.055, and 0.022, respectively, which were all far lower than the risk threshold of 1. The median concentration of cumulative exposure to the four NEOs standardized by IMI was 21.241 μg·g⁻¹, and its median EDI was 2.370 µg·kg⁻¹·d⁻¹. The maximum HQ of cumulative exposure to the four NEOs was only 0.694, which also did not exceed the risk threshold of 1. Conclusion NEOs exposure is common among the 5-year-old children in Laizhou Wan, Shandong. Although there is no obvious health risk associated with single and cumulative exposure to NEOs in the children in this area, their exposure levels of NEOs are higher than those in some foreign areas. The adverse health effects of long-term exposure to low dose of NEOs deserve our extensive attention.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

Objective:To evaluate the differential diagnostic efficacy of a predictive model of breast imaging reporting and data system (BI-RADS) classification combined with mammography radiomics classifier for various X-ray phenotype of breast lesions.Methods:A retrospective analysis was performed on 2 055 female patients who underwent mammography examination and were confirmed by pathology from May 2013 to August 2020 in Zhongda Hospital, Southeast University. Breast lesion was classified into mass or non-mass according to the fifth edition of BI-RADS. The mass was further divided into small mass (maximum diameter ≤ 2 cm) and large mass (maximum diameter>2 cm), the non-mass was further divided into asymmetric, calcification and structural distortions. By manually segmenting the region of interest of the lesion, the radiomics features were extracted and the model was constructed. Receiver operating characteristic curve and area under the curve (AUC) were used to assess the diagnostic efficacy of the BI-RADS classification, the radiomics model and the combined model for various phenotypes of breast lesions. Differences among the AUC were analyzed by the DeLong test.Results:The AUCs based on the BI-RADS classification, the radiomics model and the combined model were 0.924±0.006, 0.827±0.009 and 0.947±0.005 respectively. Compared with BI-RADS classification and the radiomics model, AUC of the combined model was the highest, and the differences were statistically significant ( Z=9.29, 14.94, P<0.001). For large mass, small mass and non-mass, combined model (AUC=0.958±0.007, 0.933±0.013, 0.939±0.008) showed the best performance when compared to the BI-RADS classification (AUC=0.937±0.010, 0.896±0.020, 0.916±0.011; Z=5.32, 3.90, 5.08, P<0.001) or the radiomics model (AUC=0.872±0.012, 0.851±0.021, 0.758±0.016; Z=7.86, 4.53, 12.13, P<0.001). The AUC of the combined model for benign and malignant asymmetric breast lesions (0.897±0.017) was higher than that of the BI-RADS classification (AUC=0.866±0.020, Z=4.27, P<0.001) and the radiomics model (AUC=0.633±0.029, Z=7.44, P<0.001); however, the AUC of the combined model for benign and malignant calcification and structural distortion of breast lesions (0.971±0.010, 0.811±0.057, respectively) was only higher than that of the radiomics model (AUC=0.827±0.021, 0.586±0.075, Z=7.40, 3.15, P<0.001), and there was no significant difference with the BI-RADS classification (AUC=0.959±0.012, 0.800±0.061, Z=1.87, 0.39, P>0.05). Conclusion:The combined model shows better differential diagnostic performance, which is valued in the clinical application.

OBJE CTIVE To establish the finger prints for Yinhuang solution for inhalation and determine the contents of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid simultaneously. METHODS Using baicalin as reference ，the fingerprints of Yinhuang solution for inhalation were established by high performance liquid chromatography （HPLC）. Relative correction factors of neochlorogenic acid and cryptochlorogenic acid were calculated by slope correction method ，using chlorogenic acid as reference ；the contents of them were calculated according to relative correction factor. The results of quantitative analysis of multi-components by single marker （QAMS）were compared with those of external standard method （ESM）. RESULTS There were 18 common peaks in the fingerprints of 10 batches of Yinhuang solution for inhalation ，and their similarities with reference fingerprint were higher than 0.90. A total of 7 common peaks were identified as baicalin ，neochlorogenic acid ，chlorogenic acid ， cryptochlorogenic acid ，isochlorogenic acid B ，3，5-di-O-caffeoylquinic acid and 4，5-di-O-caffeoylquinic acid. The linear range of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid were 0.025 0-1.247 4 μg（r＝0.999 7），0.039 3-1.178 7 μg（r＝ 0.999 9），0.031 6-1.184 1 μg（r＝0.999 9），respectively. RSDs of precision ，reproducibility and stability tests （48 h）were all lower than 1.0％. The average recoveries were 93.92％（RSD＝1.32％ ，n＝6），94.46％（RSD＝1.45％，n＝6），93.93％（RSD＝ 1.57％，n＝6）. Relative correction factors of neochlorogenic acid and cryptochlorogenic acid were 1.068 and 1.233. The contents of neochlorogenic acid and cryptochlorogenic acid determined by QAMS method were 0.301 8-0.386 3 and 0.262 5-0.362 5 mg/mL， respectively. The contents of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid by ESM were 0.302 6-0.387 2， 0.231 0- 0.334 0，0.261 6-0.361 3 mg/mL，respectively. The deviations of the content determination results of the two methods（except for chlorogenic acid ）were both not higher than 0.20％. CONCLUSIONS Established HPLC fingerprints are stable and feasible. Established QAMS method is accurate and rapid. HPLC fingerprint combined with QAMS can be used for the quality control for Yinhuang solution for inhalation ．

Immunological evasion is one of the defining characteristics of cancers, as the immune modification of an immune checkpoint (IC) confers immune evasion capabilities to tumor cells. Multiple ICs, such as programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), can bind to their respective receptors and reduce tumor immunity in a variety of ways, including blocking immune cell activation signals. IC blockade (ICB) therapies targeting these checkpoint molecules have demonstrated significant clinical benefits. This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers. Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment. In this review, we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels, including epigenetic regulation, transcriptional regulation, and post-translational modifications. In addition, we provide a summary of the medications targeting various nodes in the regulatory pathway, and highlight the potential of newly identified IC molecules, focusing on their potential implications for cancer diagnostics and immunotherapy.
Apoptosis Regulatory Proteins ; CTLA-4 Antigen/therapeutic use* ; Epigenesis, Genetic ; Humans ; Immunotherapy ; Neoplasms/therapy* ; Programmed Cell Death 1 Receptor/therapeutic use*

Objective:To investigate the application value of electroencephalogram (EEG) combined with regional cerebral oxygen saturation (rSO 2) in monitoring cerebral perfusion during carotid endarterectomy (CEA). Methods:A retrospective analysis of clinical data of 42 patients with atherosclerotic carotid artery stenosis admitted to and accepted CEA in our hospital from January 2018 to December 2019 was performed. CEA was performed under EEG combined with rSO 2 monitoring. The efficacy and safety of EEG combined with rSO 2 in monitoring cerebral perfusion abnormalities during CEA were analyzed. Results:After carotid artery occlusion, 24 patients (57.1%) had normal EEG and rSO 2; 15 (35.7%) had abnormal changes of EEG, among whom 13 (31.0%) were accompanied by rSO 2 anomaly; 16 (38.1%) had abnormal rSO 2, among whom 13 (31.0%) were accompanied by EEG anomaly. Of these 18 patients with abnormal EEG and/or rSO 2 monitoring, 17 patients recovered after increasing their blood pressure and 1 patient recovered after diverter tube usage. Intraoperative EEG and rSO 2 monitoring results were consistent (Kappa=0.745, P=0.000). The positive rates of combined monitoring, EEG alone or rSO 2 alone were 42.9%, 35.7% and 38.1%, respectively. All patients were evaluated clinically and radiologically before discharge, and no new ischemic lesions or clinical symptoms were found. Conclusions:EEG and rSO 2 monitoring are well consistent in CEA; the combined monitoring can make up for the deficiency of single monitoring to increase surgical safety.

【Objective】 To investigate the diagnostic value of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) specific antibodies IgM and IgG on coronavirus disease 2019 (COVID-19). 【Methods】 1) The test results of SARS-CoV-2 IgM/IgG antibodies and nucleic acid(NAT), which were tested by colloidal gold test and fluorescent quantitative PCR respectively, were collected from 145 febrile outpatients during early March, 2020, named Fever group, in which retrospective analysis and paired chi-square test were performed. 2) 612 cases of SARS-CoV-2 IgM/IgG antibodies test results, which were done on March 5, 2020, were collected. They were named COVID-19 group (Our hospital was provisionally assigned as a specialized hospital for COVID-19, and 1500 COVID-19 patients admitted to our hospital from February 12, 2020 to March 18, 2020). The SARS-CoV-2 IgM/IgG antibodies and NAT were respectively tested on the 30th and the 60th day after the date of discharge. The clinical application values of the antibodies was clarified by statistical analysis. 【Results】 1) In the fever group, the positive rate of SARS-CoV-2 IgM, IgG and IgM+ IgG antibodies were 26.21% (38/145), 54.48% (79/145) and 26.21% (38/145), respectively(P<0.01), and the positive rate of NAT was 4.14% (6/145), which was lower than that of antibody (P<0.01). One (1/145, 0.69%) positive NAT was implicated in initially negative IgM and IgG antibodies samples. 2) In the COVID-19 group, the positive rate of IgM antibody was low (5%) and IgG antibody was high (65%) during 2~14 days after infection, and stably increased during the 15~56 days [IgM 47.68%(277/581) vs IgG 94.15% (547/581) ], then both decreased after 57 days. The positive rates of IgM antibody and IgG antibody were 45.8% (280/612) and 93.1% (570/612) in 612 patients during hospitalization. 15 patients′ data after dischange were not collected as they were later transferred to Huoshenshan Hospital for treatment. The coronavirus NAT results of the rest 597 COVID-19 patients, tested on the 30th and 60th days after the date of discharge, were negative, and the positive rates of IgG antibody and IgM antibody were still ≥80% and ≥40% respectively at the second month after discharge. 【Conclusion】 IgM, IgG antibody against SARS-CoV-2 can be well detected by Colloidal gold method(Innovita), whose positive rate is higher than that of NAT. IgG antibody is produced earlier than IgM, and it keeps high positive rate and persists for a long time. The combination of colloidal gold antibody test and NAT can improve the diagnose rate of COVID-19 and the exclusion of suspected cases.

Objective :To analyze correlation among fasting (FBL) and postprandial blood lipids (PBL) ,blood lipid fluctuation (absolute value of PBL‐FBL) and severity of coronary artery disease .Methods :Cross‐sectional study was performed among 264 patients undergoing coronary angiography (CAG) in our hospital .According to percutaneous coronary intervention (PCI) or not based on CAG results ,patients were divided into plaque group (n＝128) and PCI group (n＝136).Gensini score was used to assess severity of coronary artery disease .Blood lipid levels and its fluctu‐ation were compared between two groups .Correlation among blood lipid levels ,blood lipid fluctuation and severity of coronary artery disease were analyzed .Results :Compared with plaque group ,there were significant rise in per‐centages of men and smokers ,waist circumference ,levels of postprandial‐fasting (P‐F ) serum LDL‐C (ΔLDL‐C ) and P‐F plasma apolipoprotein B (ΔApoB ) , and significant reduction in plasma level of P‐F apolipoprotein A1 (ΔApoA1) in PCI group , P＜0. 05 or ＜ 0. 01. Pearson correlation analysis indicated that serum fasting and post‐prandial HDL‐C levels ,plasma fasting and postprandial levels of ApoA1 and ΔApoA1 were significant inversely cor‐related with Gensini score ( r＝ －0. 130～ －0.218 , P＜0. 05 or ＜0. 01) ,and levels of plasma fasting lipoprotein a (Lp (a)) ,serum fasting and postprandial levels of free fatty acid (FFA) ,serum P‐F FFA (Δ FFA) were significant positively correlated with Gensini score ( r＝0. 139－0. 176 , P＜0.05 or ＜0.01).Multifactor linear regression anal‐ysis indicated that postprandial serum HDL‐C was protective factor for Gensini score (B＝ －22.274 , P＝0.002 ) , while postprandial serum FFA ,Δ FFA ,waist circumference and hyperlipidemia history were its influencing factors (B＝0. 388～24. 135 , P＜0. 05 or ＜0.01).Conclusion :Measurements of fasting and postprandial blood lipid levels and their fluctuation contribute to more comprehensively and objectively assessing blood lipid levels and severity of coronary disease in patients with coronary artery disease .