ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

ObjectiveTo identify the pathogen species responsible for the wilt disease of Tetradium ruticarpum in Chongqing， investigate there biological characteristics， and screen effective fungicides， so as to provide a theoretical basis for disease control in production. MethodsThe pathogen was isolated via the tissue culture method. Pathogenicity was verified according to Koch's postulates. The pathogen was identified based on morphological characteristics and multi-gene phylogenetic analysis. The mycelial growth rate method was used for biological characterization of the pathogen and fungicide screening. ResultsThe pathogen colonies were nearly circular with irregular edges， white， short， velvety aerial hyphae， and pale purple undersides. Macroconidia were colorless， sickle-shaped， with 3-5 septa， while microconidia were transparent， elliptical， aseptate or with 1-2 septa. Multi-gene phylogenetic analysis showed that the pathogen clustered in the same clade as Fusarium fujikuroi with 100% support， which， combined with morphological characteristics， identified the pathogen causing wilt of T. ruticarpum in Chongqing as F. fujikuroi. The optimal conditions for the mycelial growth of F. fujikuroi were mung bean agar （MBA） with glucose as the carbon source， beef extract and yeast powder as nitrogen sources， 28 ℃， pH 7.0， and alternating light/dark conditions. The optimal conditions for sporulation were potato dextrose agar （PDA） with glucose as the carbon source， beef extract as the nitrogen source， 28 ℃， pH 7.0， and complete darkness. Among chemical fungicides， phenazine-1-carboxylic acid exhibited the strongest inhibitory effect on F. fujikuroi. Shenqinmycin and tetramycin were the most effective bio-fungicides. ConclusionThis study is the first to report F. fujikuroi as the causal agent of wilt disease in T. rutaecarpa. The chemical fungicide phenazine-1-carboxylic acid and the bio-fungicides shenqinmycin and tetramycin showed strong inhibitory effects against F. fujikuroi.

Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

Non-alcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）， and hepatic stellate cell （HSC） activation is the key link in the progression of NAFLD to liver fibrosis. According to the theory of "Gaozhuo"， spleen deficiency and Qi stagnation， along with Gaozhuo invasion， are the causes of NAFLD progression to liver fibrosis， which reveals the pathogenesis essence of HSC activation in traditional Chinese medicine （TCM）. Among them， spleen deficiency and Qi stagnation are the root causes of the endogenous formation of Gaozhuo. Spleen deficiency indicates the insulin sensitivity decrease and glucose metabolism disorders， and Qi stagnation means the dysregulation of hepatic glucose and lipid metabolism， which creates the preconditions for HSC activation. Gaozhuo invasion is the direct cause of HSC activation， including three stages： Internal retention of Gaozhuo， turbidity and stasis stagnation， and toxic stasis and consolidation. Internal retention of Gaozhuo refers to the abnormal metabolism and deposition of hepatic lipids， as well as the microcirculatory disorders. Turbidity and stasis stagnation is the process by which lipotoxicity stimulates the transformation of HSC into myofibroblast （MFB）， and toxic stasis and consolidation represent the secretion of a large amount of extracellular matrix （ECM） by MFB to promote the fibrosis. According to the theory of Gaozhuo and the activation process of HSC， syndromes for T2DM combined with NAFLD can be classified into spleen deficiency and Qi stagnation with internal retention of Gaozhuo， spleen Qi deficiency with turbidity and stasis stagnation， and spleen Qi deficiency with toxic stasis and consolidation. Clinically， the treatment principle is to strengthen the spleen and promote Qi， resolve turbidity， and eliminate blood stasis. Both TCM compounds and monomers can effectively inhibit the HSC activation. TCM compounds can be classified into categories for regulating spleen and harmonizing liver， resolving turbidity and removing stasis， and detoxifying and removing stasis. They mainly work by improving lipid metabolism， reducing lipid accumulation in the liver， alleviating inflammatory and oxidative stress responses， inhibiting the activation and proliferation of HSC， and reducing ECM deposition， thereby delaying the progression of liver fibrosis.

Retinopathy of prematurity(ROP)is a leading cause of childhood blindness, with extremely preterm and very-low-birth-weight infants now constituting the main high-risk group. ROP progresses in two stages: early retinal microvascular degeneration and progressive vascular arrest, followed by abnormal neovascularization in the avascular area. Early oxidative and nitrosative stress—amplified by oxygen fluctuations and immature antioxidant defenses—drives the two-phase pathogenesis via hypoxia-inducible factor/vascular endothelial growth factor(HIF/VEGF), NOX/STAT3, and nuclear factor erythroid 2 related factor 2(Nrf2)-antioxidant response element(ARE)pathways, mediating apoptosis of endothelial cells, damage to barrier and pathological angiogenesis. This review systematically analyzes different oxygen-induced retinopathy(OIR)models, elucidates key signaling pathways including Notch, Wnt in physiological and pathological vascularization, with particular emphasis on the biphasic effects of Nrf2 and the differential roles of NOX signaling between phases. We also discuss the limitations of anti-VEGF therapy and oxygen management principles. Reactive oxygen species(ROS)play context-dependent roles across vaso-obliteration and neovascularization phases. Based on mechanistic insights, we propose future directions including combined/sequential interventions, ferroptosis and lipid peroxidation targeting, nano-delivery systems for enhanced bioavailability, and perinatal safety assessment strategies, aiming to provide translatable mechanistic basis for reducing pathological neovascularization while promoting physiological vascular development.

Based on the theory of "sweet-flavored medicinals retaining and restoring body fluid"， this paper proposed that the core pathogenesis of hypercoagulable state in malignant tumors is qi deficiency and fluid consumption， blood stasis and vessels stagnation， which evolves dynamically according to the pattern "qi deficiency → fluid consumption → blood stasis". Accordingly， a staged treatment system is established with the general principle of "fortifying the middle jiao， restoring fluid and activating blood circulation". In the initial stage， invigorating the spleen and boosting qi to generate body fluid， targeting the onset of middle jiao deficiency and body fluid consumption； in the middle stage， nourishing yin and unblocking collaterals to facilitate body fluid circulation， addressing the disorder of body fluid transportation and collateral injury caused by internal dryness； in the late stage， consolidating yin and resolving blood stasis to retain body fluid， resolving yin impairment， fluid exhaustion， and binding of stasis and toxin. By regulating body fluid metabolism to improve the hypercoagulable state， this system is intended to provide insights for the prevention and treatment of hypercoagulable state in malignant tumors with traditional Chinese medicine.

OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

Objective: To analyze the factors related to dual use of traditional cigarettes and e-cigarettes among middle school students in Beijing, in order to provide a scientific basis for adapting to the new situation and carrying out tobacco control among adolescents. Methods: A multi stage cluster random sampling method was used to select 15 688 and 13 607 junior and senior middle school students from 16 districts in Beijing from April to June in 2019 and 2023, respectively. Online self administered questionnaires among middle school students in Beijing were completed, including use of traditional cigarettes and e-cigarettes, exposure to second hand smoke, attitudes and perceptions towards tobacco, etc. The Chi-square test was used to compare rates, and a multiple factors Logistic regression model was used to analyze related factors of traditional cigarettes and e-cigarettes dual use among middle school students. Results: The dual use rate of traditional cigarettes and e-cigarettes in 2023 had decreased to 2.46% from 4.88% in 2019 among middle school students in Beijing. The results of the multiple Logistic regression model analysis showed that among middle school students, tobacco control anywhere at home (boys: OR =0.47, girls: OR =0.34), without anyone smoking on campus in the past month (boys: OR =0.43, girls: OR =0.26) had lower risks of dual use ( P <0.05); and middle school students strongly or slightly agreeing that smoking could bring happiness (boys: OR =4.11, 2.22, girls: OR =5.32, 3.87), believing that smoking could increase attractiveness of young people (boys: OR =3.13, girls: OR =5.81), smoking cigarettes handed over by good friends (boys: OR =4.24, girls: OR =7.21), thinking smoking in the next year (boys: OR =5.77, girls: OR =7.74) had higher risks of dual use ( P <0.05).Among boys, junior middle school students ( OR =0.50), excellent academic performance ( OR =0.36), no acceptance of free tobacco products from tobacco companies ( OR =0.38), believing that smoking couldn t refresh oneself ( OR =0.37) and smoking still could pose a health hazard though not yet addictive ( OR =0.32) had lower risks of dual use ( P <0.05);and boys with a history of secondhand smoke exposure indoor outside home ( OR =2.19), believing that quitting smoking without difficulty ( OR =2.57),smoking e-cigarettes handed over by good friends ( OR =11.27) had higher risks of dual use ( P <0.05). Among girls, no acceptance of using tobacco product labeled items ( OR =0.28) had lower risks of dual use ( P <0.05); and girls whose parents both smoke ( OR =5.53), believing that quitting smoking might not be difficult ( OR =4.44) had higher risks of dual use ( P < 0.05 ). Conclusions The dual use rate of traditional cigarettes and e-cigarettes among middle school students in Beijing has decreased. It is recommended to take the construction of smoke free families as the starting point, so as to reduce indoor second hand smoke exposure and control tobacco promotions, and promote the formation of correct tobacco control culture and moral constraints among secondary school students.

Objective:To investigate the therapeutic effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and stent implantation in the treatment of pancreaticobiliary injuries in children.Methods:A retrospective analysis was conducted on the clinical data of children diagnosed with pancreaticobiliary injury and undergoing ERCP and stent implantation at Beijing Children′s Hospital, Capital Medical University from January 2021 to December 2022. Demographic information, clinical data, endoscopic treatment methods, postoperative complications and clinical prognosis of the children were collected. The etiology, location of pancreaticobiliary injury, occurrence of complications after endoscopic treatment, and the time for improvement and recovery after endoscopic treatment were analyzed. The patients were divided into five groups according to the etiologies of pancreaticobiliary duct injuries: post-surgical, pancreatic trauma, acute pancreatitis, chronic pancreatitis, and systemic lupus erythematosus groups. They were also classified into four groups according to the sites of pancreaticobiliary duct injuries: common bile duct, pancreatic head, pancreatic body, and pancreatic tail groups. Multi-factor analysis of variance was used for comparing the time of improvement and recovery among different groups.Results:Among 22 patients, there were 8 males and 14 females, and the age was 7.5 (3.3,10.8) years. There were 19 cases of pancreatic or bile duct fistula, and 3 cases of pancreatic or bile duct stenosis. A total of 33 endoscopic procedures were performed on the 22 patients, out of which, 3 duct stenosis were failed to insert the stent because the catheter failed to pass through the stenosis site. The success rate was 91% (30/33). The pancreatic duct or bile duct stent was inserted, with the stent located at pancreatic or bile duct fistula. Postoperative complications included pancreatitis in 3 cases (9%, 3/33), hyperamylasemia in 5 cases (15%, 5/33), and postoperative infection in 4 cases (12%, 4/33). All patients were followed up for more than 1 year. Significant improvement was observed in external drainage and imaging monitoring among patients with successfully placed stents. There was no significant difference in the improvement time of ERCP in the treatment of pancreaticobile duct injury caused by different etiology ( F=0.65, P=0.637). However, there were significant differences in healing time ( F=6.46, P=0.004), among which the healing time of injuries caused by systemic lupus erythematosus was significantly different from that after surgery, trauma, acute pancreatitis and chronic pancreatitis (all P<0.05). There was no significant difference in the improvement and healing time among different injury sites (all P>0.05). Conclusions:ERCP and stent implantation can safely and effectively improve the clinical symptoms of children with pancreaticobiliary injury. Early intervention can improve long-term prognosis.