The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

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

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Objective:To analyze and evaluate the different methods in detecting anti-mitochondrial antibodies (AMA) for the diagnostic performance of primary biliary cholangitis (PBC).Methods:In this retrospective study, we collected serum samples of 37 PBC patients who were admitted to the Second Hospital of Jiaxing, from November 2022 to November 2023, 43 patients with other autoimmune diseases and 53 normal controls during the same time. The results of AMA were detected in parallel by indirect immunofluorescence assay (IIF), immunoblot tests (IB) and chemilluminescent microparticle immunoassay (CLIA). Fisher′s exact test was used to compare the count data between different groups, while a paired chi-square test was used to assess the results of the three test methods. We analyzed the performance of the three test methods; Venn diagram was used to show the consistency distribution of AMA results, the diagnostic performance of AMA for PBC were evaluated by area under receiver operating characteristic curve (ROC).Results:The positive rate of AMA in PBC group was significantly higher than that in the other two groups, and AMA was detected by CLIA which had higher positive rate (86.5%, 32/37) than the other two methods. As shown in the Venn diagram, the proportion of consistent AMA results among the three methods was 74.4%(99/133), and between IB and CLIA methods which used for detecting AMA-M2, the consistent proportion was 86.5%(115/133). Among comparison of the performance of three methods, the highest specificity (92.7%)was IIF method, and the highest sensitivity (86.5%) was CLIA method. The respective AUC of IIF, IB and CLIA methods were 0.801, 0.800 and 0.875. In the combined detection, the AUC of IIF+CLIA method was 0.942, which was better than the other two or triple combined method detection.Conclusion:For highly suspected PBC patients with negative IIF screening test, combined IB or CLIA could be used to detect AMA-M2. We recommended that clinicians should refer to the AMA results conducted by two or three methods, and preferentially recommended the IIF method combined with CLIA method for the detection of AMA.

AIM: To investigate the effect of electroacupuncture on the expression of matrix metalloproteinase-3(MMP-3), tissue inhibitor of metalloproteinase-3(TIMP-3)and collagen type III alpha 1(Col3α1)in the retina of guinea pigs with lens-induced myopia.METHODS:A total of 80 guinea pigs were randomly divided into the normal control(NC)group, negative lens-induced myopia(LIM)group, electro-acupuncture(EA)group, and sham group, with 20 guinea pigs in each group. The NC group did not receive any intervention, the LIM, EA and the sham groups were all wearing -6.0 D lens in the right eye and no lens in the left eye. The EA group was given electroacupuncture stimulation at Hegu Point and temple, and guinea pigs in the sham group were given intervention at false points. The refraction was measured by optometry, the axial length was measured by A-ultrasound, and the changes in retinal tissue structure were observed by HE staining. Quantitative polymerase chain reaction(Q-PCR)and western blot(WB)were used to detect the expression of MMP-3, TIMP-3, and Col3α1 at mRNA and protein levels before modeling and at 2 and 4 wk after modeling. RESULTS:The axial length of the negative LIM group was significantly increased compared with the NC group at 2 and 4 wk after modeling(all P<0.05), and the diopter was significantly decreased(all P<0.05); the axial length of the eye in the EA group was decreased compared with the negative LIM group(all P<0.05), and the diopter was increased(all P<0.05). HE staining showed that the boundaries of retinal tissue in the NC group were obvious and arranged regularly. The retinal thickness, the thickness of the inner and outer nuclear layers, and the number of cells were reduced and irregularly arranged in the negative LIM group. The overall structure of the retina in the group EA was relatively perfect, the arrangement was more regular, and the morphological structure of each layer of the tissue did not appear obvious abnormalities. Q-PCR and WB detection results showed that the mRNA and protein relative expression levels of MMP-3, TIMP-3, and Col3α1 in the negative LIM group were significantly higher than those in the NC group(all P<0.05); the expression levels of the EA group was significantly decreased after intervention compared with the negative LIM group(all P<0.05).CONCLUSION: Electroacupuncture can delay axial growth in negative LIM guinea pigs, and downregulate negative LIM induced expression of MMP-3, TIMP-3, and Col3α1 in the retina.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Objective: To evaluate the prevalence and consistency of screening myopia, non-cycloplegic myopia and cycloplegic myopia in children and adolescents, and to provide references for exploring the factors affecting the consistency of different definition methods. Methods: A total of 3 868 children and adolescents aged 6 to 17 years from seven schools were included in a school based cross sectional study in Shandong Province in September 2020. The prevalence of screening myopia, non cycloplegic refraction, and cycloplegic refraction at different ages and all children and adolescents were analyzed. With cycloplegic spherical equivalent ≤-0.50 D as the gold standard for myopia, and Kappa test and area under the ROC curve were used to evaluate the consistency. Results: The prevalence of cycloplegic myopia and screening myopia were 36.7% and 38.3% among children and adolescents. The prevalence of non cycloplegic myopia was 62.4%, which was significantly higher than screening myopia and cycloplegic myopia two methods in primary and junior high schools. Among 3 868 subjects, there were 3 628 (93.8%) subjects with screening myopia and 2 862 (74.0%) subjects with non cycloplegic myopia who were consistent with the gold standard for myopia. The Kappa values of screening myopia and non cycloplegic myopia were 0.87 and 0.51, and the area under the ROC curve was 0.94 (95% CI =0.93-0.95) and 0.79 (95% CI =0.78-0.81). Compared with other groups, children and adolescents aged 8 to 17 years, in junior or high school, urban residence, better presenting distance visual acuity, and astigmatism ≤1.50 D had a higher consistency in the application of screening myopia ( P <0.05). Conclusion The consistency between screening myopia and cycloplegic myopia is high, and the consistency between non cycloplegic objective myopia is low.

Objective:To evaluate the accuracy and stability of Eye-Monitor, a smart wearable device, in quantifying environmental risks related to myopia.Methods:A diagnostic test study was conducted.Forty-two subjects aged 18-25 years old were recruited from Shandong University of Traditional Chinese Medicine in December 2021.Forty-two Eye-Monitors were selected from 80 devices using the simple random sampling method.Static and dynamic tests were carried out to compare environmental risks related to myopia.The static tests included measurements under different working distances, different head tilt angles when sitting, and different light intensities.The dynamic tests included measurements under different near-work time, different outdoor activity time, different time watching computers, and different phone viewing time.Eye-Monitor with the largest sum of absolute values of total relative error was selected, Spearman rank correlation analysis was used to analyze the correlation between the set values and Eye-Monitor measurements, and the accuracy of the objectively measured values was evaluated by Bland-Altman consistency analysis.The stability of the objectively measured values from Eye-Monitor was evaluated by the coefficient of variation.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.HEC-KS-2021005KY). Written informed consent was obtained from each subject.Results:There were significant correlations between the measured values and setting values in the working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time viewing phones ( rs=0.999, 0.998, 0.999, 0.998, 0.976, 0.959, 0.992, 0.997; all at P<0.001), with the 95% limits of agreement (LoA) of-1.23-2.32 cm, -1.49-4.24°, -13.90-26.90 lx, -6.46-0.11 minutes, -4.50-1.20 minutes, -4.01-1.34 minutes, -2.54-1.94 minutes and-2.15-0.45 minutes, respectively.More than 95% of dots were within the clinically acceptable LoA.The coefficients of variation of the measured values ranged from 1.23%-2.99%, 2.39%-8.25%, 0.87%-8.03%, 1.49%-12.52%, 6.63%-13.59%, 0.00%-14.15%, 1.20%-8.33 and 1.49%-12.51%, respectively, showing good stability.Eye-Monitor had good accuracy in measuring outdoor light intensity (95% LoA: -336.50-130.00 lx). Conclusions:The smart wearable device Eye-Monitor can be used to objectively monitor working distance, head tilt angle when sitting, indoor light intensity, total near-work time, average continuous near-work time, outdoor activity time, time watching computers, and time watching phones, which are with good accuracy and stability.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.