ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids （SCFAs）-specific receptor GPR43/mitogen-activated protein kinase （MAPK） signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups： blank control group， model group， low-dose paeonol group （120 mg·kg^-1）， high-dose paeonol group （480 mg·kg^-1）， and silybin group （36.8 mg·kg^-1）. A mouse model of alcohol-induced liver disease （ALD） was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels， liver function， inflammatory cytokines， and oxidative stress markers were measured. Liver hematoxylin-eosin （HE） staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 （ZO-1）， Claudin-1， and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43， ZO-1， and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally， fecal microbiota transplantation （FMT） experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group， the model group showed significantly elevated serum lipid levels， oxidative stress， and inflammatory cytokine expression （P<0.01）. Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated （P<0.01）， while GPR43， ZO-1， and Claudin-1 protein expression levels were significantly decreased （P<0.01）. The composition and abundance of the intestinal flora were markedly altered， with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium， Parabacteroides， Erysipelothrix， and Adlercreutzia， alongside increased abundances of Clostridium butyricum， Enterococcus， and Helicobacter pylori in the model group. Compared with the model group， paeonol significantly reduced serum lipid levels， oxidative stress responses， and the expression of inflammatory cytokines in ALD mice （P<0.05， P<0.01）. It also attenuated hepatic lipid accumulation， restored intestinal barrier function， and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1， Claudin-1， and GPR43 in the colonic tissue were significantly increased （P<0.05， P<0.01）， while those of MAPK pathway-related proteins were significantly decreased （P<0.05， P<0.01）. The intestinal flora dysbiosis was effectively alleviated， rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments， supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice， which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway， thereby achieving anti-inflammatory effects and improving intestinal barrier function.

ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids （SCFAs）-specific receptor GPR43/mitogen-activated protein kinase （MAPK） signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups： blank control group， model group， low-dose paeonol group （120 mg·kg^-1）， high-dose paeonol group （480 mg·kg^-1）， and silybin group （36.8 mg·kg^-1）. A mouse model of alcohol-induced liver disease （ALD） was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels， liver function， inflammatory cytokines， and oxidative stress markers were measured. Liver hematoxylin-eosin （HE） staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 （ZO-1）， Claudin-1， and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43， ZO-1， and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally， fecal microbiota transplantation （FMT） experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group， the model group showed significantly elevated serum lipid levels， oxidative stress， and inflammatory cytokine expression （P<0.01）. Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated （P<0.01）， while GPR43， ZO-1， and Claudin-1 protein expression levels were significantly decreased （P<0.01）. The composition and abundance of the intestinal flora were markedly altered， with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium， Parabacteroides， Erysipelothrix， and Adlercreutzia， alongside increased abundances of Clostridium butyricum， Enterococcus， and Helicobacter pylori in the model group. Compared with the model group， paeonol significantly reduced serum lipid levels， oxidative stress responses， and the expression of inflammatory cytokines in ALD mice （P<0.05， P<0.01）. It also attenuated hepatic lipid accumulation， restored intestinal barrier function， and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1， Claudin-1， and GPR43 in the colonic tissue were significantly increased （P<0.05， P<0.01）， while those of MAPK pathway-related proteins were significantly decreased （P<0.05， P<0.01）. The intestinal flora dysbiosis was effectively alleviated， rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments， supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice， which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway， thereby achieving anti-inflammatory effects and improving intestinal barrier function.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

OBJECTIVE: To investigate the regulatory effect of electroacupuncture (EA) at "Neiguan" (PC6) on mitochondrial autophagy in rats with myocardial ischemia-reperfusion injury (MIRI) at different phases (ischemia and reperfusion phases), and to explore the bidirectional regulatory effects of EA at "Neiguan" (PC6) and its potential mechanism. METHODS: Forty-five male SD rats were randomly divided into 6 groups according to the random number table method, namely, sham-operation group (n=9), model-A group (n=6), model-B group (n=9), EA-A1 group (n=6), EA-B1 group (n=6), and EA-B2 group (n=9). Except the rats in the sham-operation group, the MIRI model was established in the other groups with the physical ligation and tube pushing method. In the model-A group, the samples were collected directly after ligation, and in the model-B group, the samples were collected after ligation and reperfusion. In the EA-A1 group, EA was delivered while the ligation was performed, and afterwards, the samples were collected. In the EA-B1 group, while the ligation was performed, EA was operated at the same time, and after reperfusion, the samples were collected. In the EA-B2 group, during ligation and the opening of the left anterior descending branch of the coronary artery, EA was delivered, and after reperfusion, the samples were collected. EA was performed at bilateral "Neiguan" (PC6), with a disperse-dense wave, a frequency of 2 Hz/100 Hz, a current of 1 mA, and a duration of 30 min. HE staining was employed to observe the morphology of cardiomyocytes, TUNEL was adopted to detect the apoptosis of cardiomyocytes, transcriptome sequencing was to detect the differentially expressed genes in the left ventricle, JC-1 flow cytometry was to detect the mitochondrial membrane potential (MMP) of cardiomyocytes, Western blot was to detect the protein expression of phosphatase and tensin homolog-induced kinase 1 (Pink1), Parkin and p62 in the left ventricle of rats, and ELISA was to detect the levels of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTn-I) in the rats. RESULTS: Compared with the sham-operation group, the cardiomyocytes of rats in the model-B group were severely damaged, with disordered arrangement, unclear boundaries, broken muscle fibers, edema and loose distribution; and the cardiomyocytes in the EA-B2 group were slightly damaged, the cell structure was partially unclear, the cells were arranged more regularly, and the intact cardiomyocytes were visible. Compared with the sham-operation group, the apoptosis of cardiomyocytes increased in the model-B group (P<0.001); and when compared with the model-B group, the apoptosis alleviated in the EA-B2 group (P<0.001). The differentially expressed genes among the EA-B2 group, the sham-operation group and the model-B group were closely related to cell autophagy and mitochondrial autophagy. Compared with the sham-operation group, MMP of cardiomyocytes was reduced (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle and the levels of serum CK-MB and cTn-I were elevated in the model B group (P<0.001). In comparison with model-A group, the MMP of cardiomyocytes and the levels of serum CK-MB and cTn-I were reduced (P<0.001, P<0.05), and the protein expression of Pink1 in the left ventricle rose in the EA-A1 group (P<0.01). Compared with the model-B group, MMP of cardiomyocytes increased (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased (P<0.001) in the EA-B1 group and the EA-B2 group. When compared with the EA-A1 group, MMP of cardiomyocytes increased (P<0.001), and the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased in the EA-B1 group (P<0.01). CONCLUSION EA at "Neiguan" (PC6) can ameliorate MIRI in rats, which may be achieved through the Pink1/Parkin-mediated mitochondrial autophagy pathway. EA can alleviate myocardial injury by enhancing mitochondrial autophagy at the ischemia phase, and it can reduce reperfusion injury by weakening mitochondrial autophagy at the reperfusion phase.
Animals ; Electroacupuncture ; Male ; Myocardial Reperfusion Injury/metabolism* ; Rats, Sprague-Dawley ; Rats ; Acupuncture Points ; Autophagy ; Humans ; Mitochondria/genetics*

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.

OBJECTIVE To provide standardized whole-process guidance on drug traceability codes for medical institutions in Sichuan province， ensuring medication safety and compliance with medical insurance supervision requirements. METHODS Based on evidence-based principles and expert consensus， Expert Consensus on Whole-process Management of Drug Traceability Codes in Medical Institutions of Sichuan Province （hereinafter referred to as the Consensus） was formulated through systematic literature review， field investigations， establishment of a multidisciplinary expert committee and multiple rounds of questionnare consultation via the modified Delphi method， and finalized through consensus meetings. RESULTS & CONCLUSIONS The Consensus clarifies key operating procedures for code verification， code assignment and code return， whole-process operational standards for drug warehouse acceptance and storage， drug warehouse outbound delivery and pharmacy acceptance check， drug distribution and dispensing in pharmacy and intravenous admixture center， medication administration in nursing units and examination departments， as well as drug return process. Key recommendations are proposed such as improving the core functions of the drug traceability system， unifying the hospital-wide traceability code database， strengthening the management of traceability codes for backup medications， establishing a management organization and institutional framework， and optimizing the architectural design and data governance requirements of the drug traceability system. The release of the Consensus will provide scientific， standardized and implementable practical guidelines for medical institutions of Sichuan province， helping to improve closed-loop management of the drug traceability system， strengthen medication safety and fulfil medical insurance fund supervision.

OBJECTIVE To establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.

ObjectiveTo validate the efficacy of Yunpi Huatan Tongqiao prescription （YHTP） in down-regulating glycolysis to modulate microglia phenotype and improve inflammation and cognitive memory deficits in obstructive sleep apnea （OSA） mice. MethodForty-eight male Balb/C mice were randomly divided into a normal group， a model group， a montelukast sodium group （30 mg·kg^-1）， and low， medium， and high dose groups of YHTP （8.28， 16.56， and 33.12 g·kg^-1）， with 8 mice in each group. All groups， except the normal group， received intraperitoneal injections of lipopolysaccharide （LPS） and underwent chronic intermittent hypoxia （CIH） modeling for 4 weeks. Subsequently， the mice were treated with medications for 4 weeks and then sampled. Animal behavioral tests assessed memory impairment due to hypoxia. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure mRNA expression levels of M1-associated inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and markers such as T lymphocyte activation antigen （CD86） and inducible nitric oxide synthase （iNOS）， as well as M2-associated inflammatory factors interleukin-10 （IL-10）， transforming growth factor-β （TGF-β）， and the marker mannose receptor （CD206） in hippocampal tissue. Western blot was employed to detect differences in the expression of M1 and M2 microglia phenotypic markers （CD86， CD206） and glycolysis-related proteins glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phosphofructokinase （PFKM）， pyruvate kinase 2 （PKM2）， and monocarboxylic acid transporter 1 （MCT1）. ResultBehavioral tests showed that compared to the results in the normal group， the Y-maze autonomous alternation rate was significantly reduced in the model group （P<0.01）. The latency time for the target hole in the Barnes' maze during the training period （days 2， 3， 4） and testing period （days 5， 12） was significantly increased （P<0.05， P<0.01）. M1 glial cell markers CD86 and iNOS， as well as inflammatory factors IL-1β and TNF-α mRNA， were significantly elevated （P<0.01）. In contrast， the mRNA expression of M2 glial cell markers IL-10， CD206， and TGF-β was significantly reduced （P<0.01）. The protein expression of glycolytic proteins HK2， PFKM， PKM2， MCT1， and the M1 marker CD86 was significantly increased （P<0.05， P<0.01）， while M2 marker CD206 protein expression was significantly decreased （P<0.01）. Compared to the results in the model group， the Y-maze autonomous alternation rate was significantly increased in the medium and high dose groups of YHTP （P<0.05， P<0.01）. The latency time for the target hole during the training （day 4） and testing periods （days 5， 12） was significantly reduced （P<0.01）. Real-time PCR results indicated that mRNA expression levels of M1-related pro-inflammatory factors in the hippocampal tissue were significantly reduced in the low， medium， and high dose groups of YHTP （P<0.01）， while M2-related inflammatory factors' mRNA expression was significantly increased （P<0.01）. Western blot results showed that in the medium and high dose groups of YHTP， the expression of the M1 marker CD86 in the hippocampus was reduced， whereas the expression of the M2 marker CD206 was significantly increased （P<0.01）， with a significant decrease in the expression of glycolysis-related proteins （P<0.01）. ConclusionYHTP can improve inflammation and cognitive impairment induced by hypoxia in OSA model mice. This is achieved by downregulating glycolysis in brain microglia， inhibiting M1 activation， reducing pro-inflammatory factor release， and promoting M2 activation， thereby exerting a therapeutic effect on inflammation and cognitive impairment caused by OSA.

Immune-related nephropathy (IRN) refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal failure. The pathogenesis of IRN is not fully understood; therefore, treatment is challenging. Traditional Chinese medicines (TCMs) have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy, lupus nephropathy, and diabetic nephropathy. The underlying mechanisms mainly include its inhibition of inflammation; improvements to renal interstitial fibrosis, oxidative stress, autophagy, apoptosis; and regulation of immunity. In this review, we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions, herbs, and bioactive compounds in treating IRN, as well as the potential mechanisms, intending to provide a reference for the future study of TCM as IRN treatments.