Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver injury of unknown etiology. The onset of this disease involves the activation and recruitment of diverse immune and non-immune cells, which in turn trigger hepatic damage. Immune checkpoint molecules (ICM) are expressed on the surface of multiple cell types. By regulating cellular functional states, they help limit the intensity and duration of immune responses, thereby preventing excessive inflammation and tissue damage, and maintaining immune homeostasis. In AIH, however, this natural "braking" mechanism is impaired, leading to aberrant activation of both immune and non-immune cells and the breakdown of immune homeostasis. Consequently, ICM are likely to play a critical role in the pathogenesis of AIH. A deeper understanding of the function of ICM in AIH not onlyadvances our insight into the disease mechanism, but also suggests that targeting these molecules may represent a promising therapeutic strategy for the treatment of AIH.

Objective To determine the molecular mechanism of Yuchang granule (YCG) against ulcerative colitis （UC） by network pharmacology-based approach combined with molecular docking. Methods TCMSP and HIT database were utilized to search the active components and potential targets of YCG. The effective targets of UC were obtained by GeneCards, CTD, and DisGeNET databases. Venn Diagram was exploited to receive common targets of YCG and UC. Network maps of the TCM of YCG-active component-common targets were constructed by the Cytoscape software to gain key active components. Protein-protein interaction （PPI） of common targets was constructed by the STRING database obtaining core common targets. The mechanism and therapeutic effects of YCG on UC were explored via gene ontology （GO） and the biological pathway （KEGG） enrichment analyses. Molecular docking technology was carried out to verify the combination of core active components with key common targets. Results 98 active components and 237 potential targets were sieved from YCG, and 1061 effective targets were screened from UC. 94 common targets of YCG and UC were regarded as potential therapeutic targets. Bioinformatics analysis revealed that quercetin, luteolin, β-quebrachol, stigmasterol, and kaempferol may be the potential candidate agents. Tumor necrosis factor （TNF）, serine/threonine-protein kinase （AKT1）, tumor protein p53 （TP53）, interleukin-6 （IL-6） and IL-1β could become potential therapeutic targets. KEGG showed pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and IL-17 signaling pathway might play an important role in YCG against UC. Molecular docking results showed that quercetin combined well with TNF, AKT1, and TP53. And stigmasterol did well with AKT1. Conclusion This study comprehensively illustrated the potential candidate agents, potential therapeutic targets, and pathways of YCG against UC. It also illustrated that YCG could act on multiple targets through multi-pathway treating UC.

OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Objective To explore a feasible simplified premedication protocol for preventing hypersensitivity reactions to taxanes. Methods The electronic medical record system was used to search for data from 49 patients with advanced gastric cancer who received paclitaxel liposome treatment for the first time in the gastroenterology department of Shanghai Changhai Hospital from 2021-06-01 to 2024-06-30, including premedication protocols, allergic reactions, and other adverse reactions. Results Among 31 patients, the premedication regimen included oral dexamethasone 9 mg at 12 h and 6 h prior to liposomal paclitaxel, plus oral loratadine 10 mg and oral ranitidine 150 mg at 12 h prior to treatment. Among 18 patients, the regimen included oral dexamethasone 9 mg at 12 h and 6 h prior to treatment, and oral loratadine 10 mg at 12 h prior to treatment. None of the patients experienced allergic reactions. The incidence of other adverse reactions did not differ significantly between the two groups（P>0.05）. Conclusion Based on literature and practice, a dual simplified premedication protocol of oral corticosteroids（GC）combined with oral H1 receptor blockers（H1RA）was proposed, which provided a new idea for doctors. Further clinical studies are needed to verify its effectiveness.

Objective To explore a feasible simplified premedication protocol for preventing hypersensitivity reactions to taxanes. Methods The electronic medical record system was used to search for data from 49 patients with advanced gastric cancer who received paclitaxel liposome treatment for the first time in the gastroenterology department of Shanghai Changhai Hospital from 2021-06-01 to 2024-06-30, including premedication protocols, allergic reactions, and other adverse reactions. Results Among 31 patients, the premedication regimen included oral dexamethasone 9 mg at 12 h and 6 h prior to liposomal paclitaxel, plus oral loratadine 10 mg and oral ranitidine 150 mg at 12 h prior to treatment. Among 18 patients, the regimen included oral dexamethasone 9 mg at 12 h and 6 h prior to treatment, and oral loratadine 10 mg at 12 h prior to treatment. None of the patients experienced allergic reactions. The incidence of other adverse reactions did not differ significantly between the two groups（P>0.05）. Conclusion Based on literature and practice, a dual simplified premedication protocol of oral corticosteroids（GC）combined with oral H1 receptor blockers（H1RA）was proposed, which provided a new idea for doctors. Further clinical studies are needed to verify its effectiveness.

Objective To explore the principle of antibacterial drug therapy and the strategy of program optimization in elderly patients with Helicobacter pylori（Hp）. Methods The common therapeutic regimen of Hp was summarized, and the better therapeutic regimen of elderly Hp patients was screened ultimately. Results Amoxicillin and cefuroxime were relatively safe compared with other recommended antibacterial drugs. Using other commonly antibiotics for Hp should pay attention to the disease of patients and current drug. Conclusion Elderly patients usually suffered from a variety of diseases and required multiple drugs. The application of therapeutic regimen for elderly patients with Hp should be supposed to fully weigh the risks and benefits.

OBJECTIVE To optimize the extraction process of polysaccharides from Abelmoschus manihot flowers， and to investigate the antioxidant， moisturizing and hygroscopicity activities of the polysaccharides.METHODS The optimal ratio of composite enzymes was determined by orthogonal experiments， and the extraction process of polysaccharides was optimized by single-factor experiments and Box-Behnken response surface methodology， and validated. The scavenging rates of 2，2′-azino-bis （3-ethylbenzothiazoline-6-sulfonic acid） （ABTS） free radicals， hydroxyl free radicals， and superoxide anion free radicals， as well as the total reducing ability of the polysaccharides were investigated by the ABTS method， Fenton-salicylic acid colorimetric method， pyrogallol autoxidation method， and potassium ferricyanide reduction method， respectively. The moisturizing and hygroscopicity activities of the polysaccharides were evaluated by the weighing method.RESULTS The optimal ratio of composite enzymes was 136 000 U of papain， 125 000 U of pectinase，and 5 000 U of cellulase. The optimal extraction process was as follows： enzymatic hydrolysis time of 2.8 h， enzymatic hydrolysis temperature of 57.50 ℃， pH of the sodium dihydrogen phosphate-disodium hydrogen phosphate buffer was 5.5， and solid-to-liquid ratio of 1∶40. The results of three experiments showed that the average polysaccharides extraction rate of 23.595%， with an RSD of 0.90%. The scavenging rates of ABTS free radicals， hydroxyl free radicals， superoxide anion free radicals， and total reducing ability were 81.759%， 87.110%， 54.244%， and 1.129 （the mass concentrations of polysaccharides were 10、 5、 10， and 10 mg/mL， respectively）， respectively. At relative humidity of 43% for 12 h， the moisturizing rate and hygroscopicity rate of polysaccharides were 99.387% and 100.478%， respectively； at relative humidity of 83% for 12 h， they were 99.764% and 100.455%， respectively.CONCLUSIONS The optimal extraction process of polysaccharides from A.manihot flowers based on the composite enzymes is stable and feasible； the polysaccharides obtained under this process have good antioxidant， moisturizing， and hygroscopicity activities.

ObjectiveTo explore the effects of electroacupuncture at governor vessel or Jiaji acupoints on the activation of lumbar spinal cord neurons and the recovery of motor function in paralyzed hind limbs in rats with complete transection of spinal cord injury. MethodsTwenty adult female SD rats were selected. Among them， 15 rats underwent the complete transection of the 10th thoracic spinal cord and were randomly divided into the Control group， the electroacupuncture at governor vessel acupoints （GV） group and the electroacupuncture at Jiaji acupoints （JJ） group， with 5 rats in each group. The other 5 rats served as the Normal group. Electroacupuncture treatment was initiated 3 days after surgery in the GV and JJ groups and performed every other day. Basso-Beatti-Bresnahan （BBB） behavioral score was evaluated weekly. Eight weeks after the operation， cortical motor evoked potential （CMEP） detection was performed， followed by perfusion fixation， tissue harvest， frozen sectioning， and immunofluorescence staining experiments. Results① Both electroacupuncture treatments activated the expression of the excitatory marker c-Fos in L1 spinal cord neurons. The c-Fos⁺ activated neurons were mainly distributed in lamina Ⅳ， Ⅴ and Ⅶ of the L1 spinal cord， while no c-Fos⁺ neuron was observed in the Normal group and the Control group. The percentages of c-Fos⁺ neurons activated by electroacupuncture in the GV group and the JJ group were （10.23±0.15） % and （10.77±1.12） %， respectively， and there was no significant difference between the two electroacupuncture groups. ② vGluT1⁺ proprioceptive afferent nerve fibers were mainly distributed in the dorsal horn and lamina Ⅶ of intermediate zone of L1 spinal cord gray matter. In the dorsal horn of L1 spinal cord， the relative fluorescence intensity of vGluT1⁺ nerve fibers in the GV group and the JJ group were greater than that in the Control group， and that in the JJ group was greater than that in the GV group. In the lamina Ⅶ in intermediate zone of L1 spinal cord， where the central pattern generator （CPG） for hindlimb rhythmic movement is located， the relative fluorescence intensity of vGluT1⁺ nerve fibers in the GV group and the JJ group were significantly higher than that in the Control group， and the JJ group was also higher than the GV group； The lamina Ⅶ neurons innervated by vGluT1⁺ axon terminals were activated to express the excitatory marker c-Fos in the GV group and the JJ group. ③ The immunofluorescence staining results of acetylcholinesterase （ChAT） in the ventral horn of L4 spinal cord of each group showed that the number of surviving ChAT⁺ motor neurons in the GV group （19.1±3.4， P=0.000 2） and JJ group （19.0±2.9， P=0.000 2） were higher than that in the Control group （9.9±1.9）. ④ The quantitative analysis of the vGluT2⁺ excitatory axonal terminals， vGAT⁺ inhibitory axonal terminals， and the ratio of vGluT2⁺/vGAT⁺ axonal terminals ［reflecting the excitation/inhibition （E/I） balance of motor neurons］ innervating ChAT⁺ motor neurons in the ventral horn of the L4 spinal cord revealed that all three indices were significantly higher in the GV and JJ groups than in the Control group. Moreover， the E/I ratio of motor neurons in the two electroacupuncture groups gradually reached the same level as normal and showed no statistical difference from the Normal group. ⑤ The electrophysiological and behavioral detection results showed that compared with the Control group， the latencies of CMEP in the GV group and the JJ group shortened， while their amplitudes increased. The BBB score of paralyzed hindlimbs showed that after 8 weeks of treatment， the scores of both the GV group （4.25±1.26， P=0.023 4） and the JJ group （4.75±0.96， P=0.000 2） were higher than those of the Control group （1.80±1.30）， but there was no statistical difference between the two electroacupuncture groups. ConclusionElectroacupuncture at GV or JJ acupoints may promote the afferent of vGluT1⁺ proprioceptive nerve fibers into the spinal cord， indicating the possibility to activate CPG neurons in lamina Ⅶ of L1 spinal cord； facilitate the survival of motor neurons in the L4 spinal cord and restore their excitatory/inhibitory balance， improving the motor function of the paralyzed hindlimbs in rats.

Objective : To investigate the prevalence of negative emotions in hospitalized youth patients with type 2 diabetes(T2DM) and its correlation with coping strategies and psychological resilience. Methods : 141 youth T2DM patients who met the research standards were selected. Blood glucose related indicators, blood pressure, body mass index(BMI), diabetes chronic complications screening results and other data were collected. The basic information and disease related information questionnaire, self-rating depression scale(SDS), self-rating anxiety scale(SAS), diabetes distress scale(DDS), medical coping modes questionnaire(MCMQ) and Connor-Davidson resilience scale(CD-RISC) were completed. Results: Among 141 hospitalized youth T2DM patients, 37.6% were combined with depression, 32.6% were combined with anxiety, and 35.5% were combined with diabetic distress(DD). Univariate analysis showed that systolic blood pressure(P<0.01), educational level, and the form of hospitalization expenses(P<0.05) were significantly correlated with depression. Marital status(P<0.01), family residence, blood glucose monitoring methods, and the last fasting blood glucose(P<0.05) were significantly correlated with anxiety. BMI, whether it was first diagnosed or treated(P<0.01), gender, occupation, disease course, weekly blood glucose monitoring frequency, and the presence of chronic complications(P<0.05) were significantly correlated with DD. In multivariate analysis, systolic blood pressure(P<0.01), educational level, and the form of hospitalization expenses were significantly correlated with depression, marital status(P<0.05) was significantly correlated with anxiety; BMI and weekly blood glucose monitoring frequency(P<0.01) were significantly correlated with DD. SDS, SAS, total scores and dimensions of DDS were negatively correlated with the total score and dimensions of CD-RISC(rs=-0.182--0.467, P<0.05 or 0.01), and positively correlated with the yielding coping strategies(rs=0.177-0.271,P<0.05 or 0.01). SAS,total scores and dimensions of DDS were positively correlated with avoiding coping strategies(rs=0.237-0.419,P<0.05 or 0.01). The total and dimensions of CD-RISC were positively correlated with facing coping strategies(rs=0.215-0.349,P<0.05 or 0.01),and negatively correlated with yielding coping strategies(rs=-0.234--0.325,P<0.01). Conclusion More than 30% of hospitalized youth T2DM may experience negative emotions such as depression,anxiety,and DD. The occurrence of negative emotions in such patients may be related to disease management or socio-economic issues such as systolic blood pressure,educational level,hospitalization expenses,marital status,BMI,and frequency of blood glucose monitoring,as well as decreased psychological resilience and negative coping strategies.

Using a novel(OH)n-C60@SiO2@Tm2O3@Ca5(PO4)3(OH)quaternary nano-particles/cross-linked chitosan coated open-tubular capillary column(QNPsC-OTCC)as the analytical column,a new method for highly selective determination of taurine(TAU)in functional drinks using pre-column derivatization capillary electrochromatography coupled with electrochemiluminescence(CEC-ECL)detection was established.In the experiments,it was found that adding hexamethylenetetramine as a co-catalyst in N-methylation derivative reaction could quantitatively convert TAU into a single derivative product that cuold be detected by ECL.With the help of Ru(bpy)32+reagent,the ECL peak intensity of TAU derivative was increased by more than 1000 times compared to the original TAU.In addition,a Ru-containing d-f cyano-bridged heterometallic coordination polymer modified platinum electrode was used instead of a bare platinum electrode as working electrode for ECL detection,which resulted in a further increase of the peak response of TAU derivatives about 5.7 times.Under optimized analytical conditions,by using betastatin hydrochloride(BSH)as the internal standard and simultaneously derivatized with TAU,the relative ratio of peak intensity of TAU and BSH derivatives showed a linear relationship with the initial TAU concentration in a two-segment ranges of 0.2-6.0 mmol/L and 6.0-10 mmol/L.The limit of detection of TAU was 0.09 mmol/L(S/N=3).The developed method was applied to determination of TAU contents in four commercial functional drink samples,and the relative standard deviations(RSDs)for relative intensity ratio were less than 0.9％,and the recoveries were in the range of 95.0％～102.0％,indicating good practicability of the method.