OBJECTIVE To study the effects of Ro 64-6198,a selective nociceptin/orphanin FQ receptor(NOPR)agonist,on heroin self-administration and drug-seeking behavior in rats.METHODS Rats were trained to self-administer heroin intravenously at a dose of 0.05 mg·kg-1 under a fixed ratio 1(FR1)reinforcement schedule.Heroin motivation was assessed using a progressive ratio(PR)schedule.Firstly,a stable heroin self-administered rat model was established before the effects of Ro 64-6198 on heroin rewarding under the FR1 schedule were observed.After three days of self-administration recovery training,the effects of Ro 64-6198 on heroin reward motivation were observed under the PR3-4 schedule.Following extinction,the reinstatement of heroin seeking induced by either conditioned cues or heroin priming was evaluated in rats withdrawn from self-administration.The expressions of cAMP response element-binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the ventral tegmental area(VTA)were analyzed using Western blotting,while the expression of the NOPR in neurons in the VTA was examined through immunofluorescence staining.RESULTS Pretreatment with 3 mg·kg-1 Ro 64-6198 significantly reduced active responses and heroin infusions during FR1 testing,as well as decreased breakpoints,indicating reduced motivation under the PR schedule.At a dose of 1 mg·kg-1,Ro 64-6198 markedly attenuated the reinstatement of heroin-seeking behavior induced by conditioned cues or heroin priming.Furthermore,the administration of SB-612111,an NOPR antagonist,blocked the inhibitory effects of Ro 64-6198 on cue-induced heroin-seeking,although SB-612111 alone had no effect on heroin-seeking behavior.Ro 64-6198 treatment also suppressed the reduction of both phos-phorylated CREB(p-CREB)and BDNF levels in the VTA and the decreased expression of NOPR and p-CREB in dopaminergic neurons of the VTA.CONCLUSION These results demonstrate that Ro 64-6198 can mitigate heroin-seeking behavior through NOPR activation and CREB/BDNF pathway in the VTA.This study is expected to offer evidence for its potential as a clinical treatment for heroin addiction and relapse.

Inflammatory bowel disease (IBD) is a chronic and nonspecific disease affected by both genetic and environmental factors. Ecological and social environmental factors, including air pollutants, heavy metals, industrial pollutants and organic pollutants, diet, and lifestyle, influence the occurrence and development of IBD and regulate IBD gene expression through epigenetics and gut microbiota. This article summarizes the role of environmental factors in IBD and explores the ways in which they influence the regulation of gene expression.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with unclear etiology. Existing studies indicate that diet plays an important role in both the pathogenesis and prognosis of IBD. This review summarizes clinical evidence regarding the association between diet and the development of IBD, analyze the current nutritional status of the IBD population at the prognosis level and underlying mechanisms of dietary interventions in disease management, and explores the application of precision nutrition in personalized care. The review ultimately aims to provide guidance for developing more precise and personalized dietary management strategies for IBD patients.

[Objective]To summarize Professor SHU Qijin's clinical experience in the diagnosis and treatment of palpitations induced by antitumor therapy.[Methods]Through outpatient apprenticeship,it systematically collected and analyzed clinical cases in which Professor SHU managed palpitations induced by antitumor therapies.Relevant classical treatises on traditional Chinese medicine(TCM)and modern literature were reviewed to summarize Professor SHU's understanding of the etiology and pathogenesis,characteristics of syndrome differentiation and treatment,as well as the composition,compatibility principles and clinical application of commonly used formulas.One representative medical case was selected for in-depth analysis as supporting evidence.[Results]Professor SHU believes that the pathogenesis of palpitations induced by antitumor therapy is primarily based on Qi and Yin deficiency.Therefore,the therapeutic approach emphasizes replenishing Qi and nourishing Yin as the foundation,with an additional focus on nourishing the heart meridian.Modified Shengmai Drink is commonly prescribed and adjusted according to the patient's condition.Holistic strategies are adopted to harmonize both the body and the mind,attending to both the physical form and spirit,while balancing warming and cooling interventions to regulate Yin and Yang.The TCM pattern diagnosis of the cited case was palpitation,with Qi and Yin deficiency as the root cause,and blood stasis and phlegm-dampness as the secondary symptoms,combined with Yang deficiency.It was treated by modified Shengmai Drink to benefit Qi and nourish Yin,with favorable therapeutic outcomes.[Conclusion]Professor SHU's clinical practice in managing palpitations induced by antitumor therapies emphasizes deficiency of both Qi and Yin as the fundamental pathogenesis.He advocates a comprehensive treatment principle that integrates replenishing Qi and nourishing Yin,harmonizing the body and mind,and employing both warming and cooling strategies according to clinical presentation.Professor SHU attaches great importance to clinical flexibility and individualized treatment adjustments,demonstrating rich clinical experience and remarkable therapeutic efficacy,which provide valuable guidance for wider clinical application.

Inflammatory bowel disease (IBD) is a chronic and nonspecific disease affected by both genetic and environmental factors. Ecological and social environmental factors, including air pollutants, heavy metals, industrial pollutants and organic pollutants, diet, and lifestyle, influence the occurrence and development of IBD and regulate IBD gene expression through epigenetics and gut microbiota. This article summarizes the role of environmental factors in IBD and explores the ways in which they influence the regulation of gene expression.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with unclear etiology. Existing studies indicate that diet plays an important role in both the pathogenesis and prognosis of IBD. This review summarizes clinical evidence regarding the association between diet and the development of IBD, analyze the current nutritional status of the IBD population at the prognosis level and underlying mechanisms of dietary interventions in disease management, and explores the application of precision nutrition in personalized care. The review ultimately aims to provide guidance for developing more precise and personalized dietary management strategies for IBD patients.

OBJECTIVE To study the effects of Ro 64-6198,a selective nociceptin/orphanin FQ receptor(NOPR)agonist,on heroin self-administration and drug-seeking behavior in rats.METHODS Rats were trained to self-administer heroin intravenously at a dose of 0.05 mg·kg-1 under a fixed ratio 1(FR1)reinforcement schedule.Heroin motivation was assessed using a progressive ratio(PR)schedule.Firstly,a stable heroin self-administered rat model was established before the effects of Ro 64-6198 on heroin rewarding under the FR1 schedule were observed.After three days of self-administration recovery training,the effects of Ro 64-6198 on heroin reward motivation were observed under the PR3-4 schedule.Following extinction,the reinstatement of heroin seeking induced by either conditioned cues or heroin priming was evaluated in rats withdrawn from self-administration.The expressions of cAMP response element-binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the ventral tegmental area(VTA)were analyzed using Western blotting,while the expression of the NOPR in neurons in the VTA was examined through immunofluorescence staining.RESULTS Pretreatment with 3 mg·kg-1 Ro 64-6198 significantly reduced active responses and heroin infusions during FR1 testing,as well as decreased breakpoints,indicating reduced motivation under the PR schedule.At a dose of 1 mg·kg-1,Ro 64-6198 markedly attenuated the reinstatement of heroin-seeking behavior induced by conditioned cues or heroin priming.Furthermore,the administration of SB-612111,an NOPR antagonist,blocked the inhibitory effects of Ro 64-6198 on cue-induced heroin-seeking,although SB-612111 alone had no effect on heroin-seeking behavior.Ro 64-6198 treatment also suppressed the reduction of both phos-phorylated CREB(p-CREB)and BDNF levels in the VTA and the decreased expression of NOPR and p-CREB in dopaminergic neurons of the VTA.CONCLUSION These results demonstrate that Ro 64-6198 can mitigate heroin-seeking behavior through NOPR activation and CREB/BDNF pathway in the VTA.This study is expected to offer evidence for its potential as a clinical treatment for heroin addiction and relapse.

Objective:To compare postoperative complications between acellular dermal matrix（ADM）and direct suture for tongue mucosa defect repair during lingual mucosa urethroplasty.Methods:A retrospective analysis was conducted on 106 patients with anterior urethral stricture who underwent lingual mucosal urethroplasty at the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to July 2024. According to the needs of urethral reconstruction，lingual mucosa was harvested（graft length 0.5 cm longer than the stricture length）. Using an instrumental variable method based on the surgeon’s preference，the tongue wound was repaired either with ADM or direct suture. The ADM group included 56 patients，aged（46.2±18.7）years；diabetes in 8 cases（14.3%），hypertension in 15 cases（26.8%），cardiopulmonary dysfunction in 3 cases（5.3%）；stricture location：penile segment in 44 cases（78.6%），penoscrotal junction in 12 cases（21.4%）；etiology：lichen sclerosus in 8 cases（14.3%），urethritis in 8 cases（14.3%），trauma in 24 cases（42.9%），and re-stricture after hypospadias surgery in 16 cases（28.6%）；maximum urinary flow rate（5.8±2.9）ml/s；graft length（4.02±1.72）cm. The direct suture group included 50 patients，aged（45.8±19.2）years；diabetes in 6 cases（12.0%），hypertension in 12 cases（24.0%），cardiopulmonary dysfunction in 2 cases（4.0%）；etiology：lichen sclerosus in 6 cases（12.0%），urethritis in 8 cases（16.0%），trauma in 25 cases（50.0%），and re-stricture after hypospadias surgery in 11 cases（22%）；stricture location：penile segment in 36 cases（72.0%），penoscrotal junction in 14 cases（28.0%）；maximum urinary flow rate（6.2±3.1）ml/s；graft length（4.18±1.68）cm. There were no statistically significant differences in the above baseline characteristics between the two groups（ P>0.05）.ADM group after electrocautery hemostasis，an ADM patch tailored to the wound size was used to cover the donor site. The edges of the ADM were overlapped with the wound margin and sutured to the submucosal layer using interrupted 4-0 polyglactin sutures. Direct suture group after electrocautery hemostasis，the wound was stretched into a diamond shape and closed in layers by suturing the mucosal layer down to the muscle layer using interrupted 4-0 polyglactin sutures. The primary outcome measures were postoperative tongue complications including hemorrhage，hematoma，and infection（Clavien-Dindo classification）. Secondary outcomes included VAS pain scores，functional recovery（difficulty drinking，difficulty eating，speech impairment，limited mouth opening），and sensory recovery（sensory disturbance，taste disturbance）. Results:The follow-up period ranged from 6 to 24 months，with a mean of 9.2 months. The 6-month follow-up rate was 100%. No Clavien-Dindo grade Ⅲ or higher complications（hemorrhage，hematoma，infection）occurred by the end of follow-up. Regarding secondary outcomes，the VAS pain score on postoperative day 1 was significantly better in the ADM group than in the suture group［0（0，3）vs. 2（0，3），P=0.013］.Functional impact：The incidence of difficulty drinking［24 cases（42.9%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 21 cases（42.0%）］，difficulty eating［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］，and speech impairment［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］on postoperative day 1，day 7，and within the first month，respectively，was significantly lower in the ADM group（all P<0.05）. On postoperative day 1 and day 7，the incidence of limited mouth opening was higher in the ADM group［0 cases vs. 6 cases（12.0%），0 cases vs. 6 cases（12.0%）］（ P<0.05）.Sensory recovery：The incidence of taste disturbance was higher in the ADM group at 7 days［8 cases（14.3%）vs. 0 cases］，1 month［8 cases（14.3%）vs. 0 cases］，and 3 months［8 cases（14.3%）vs. 0 cases］postoperatively（ P<0.05）. The incidence of sensory disturbance was higher in the ADM group at 1 day［20 cases（35.7%）vs. 6 cases（12.0%）］，7 days［16 cases（28.6%）vs. 6 cases（12.0%）］，and 1 month［16 cases（28.6%）vs. 6 cases（12.0%）］postoperatively（ P<0.05）. Pain scores and complication rates were zero in both groups after 6 months. Conclusions:ADM repair improves early recovery but may increase transient sensory complications. Both methods are safe for clinical application.

Objective:To compare postoperative complications between acellular dermal matrix（ADM）and direct suture for tongue mucosa defect repair during lingual mucosa urethroplasty.Methods:A retrospective analysis was conducted on 106 patients with anterior urethral stricture who underwent lingual mucosal urethroplasty at the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to July 2024. According to the needs of urethral reconstruction，lingual mucosa was harvested（graft length 0.5 cm longer than the stricture length）. Using an instrumental variable method based on the surgeon’s preference，the tongue wound was repaired either with ADM or direct suture. The ADM group included 56 patients，aged（46.2±18.7）years；diabetes in 8 cases（14.3%），hypertension in 15 cases（26.8%），cardiopulmonary dysfunction in 3 cases（5.3%）；stricture location：penile segment in 44 cases（78.6%），penoscrotal junction in 12 cases（21.4%）；etiology：lichen sclerosus in 8 cases（14.3%），urethritis in 8 cases（14.3%），trauma in 24 cases（42.9%），and re-stricture after hypospadias surgery in 16 cases（28.6%）；maximum urinary flow rate（5.8±2.9）ml/s；graft length（4.02±1.72）cm. The direct suture group included 50 patients，aged（45.8±19.2）years；diabetes in 6 cases（12.0%），hypertension in 12 cases（24.0%），cardiopulmonary dysfunction in 2 cases（4.0%）；etiology：lichen sclerosus in 6 cases（12.0%），urethritis in 8 cases（16.0%），trauma in 25 cases（50.0%），and re-stricture after hypospadias surgery in 11 cases（22%）；stricture location：penile segment in 36 cases（72.0%），penoscrotal junction in 14 cases（28.0%）；maximum urinary flow rate（6.2±3.1）ml/s；graft length（4.18±1.68）cm. There were no statistically significant differences in the above baseline characteristics between the two groups（ P>0.05）.ADM group after electrocautery hemostasis，an ADM patch tailored to the wound size was used to cover the donor site. The edges of the ADM were overlapped with the wound margin and sutured to the submucosal layer using interrupted 4-0 polyglactin sutures. Direct suture group after electrocautery hemostasis，the wound was stretched into a diamond shape and closed in layers by suturing the mucosal layer down to the muscle layer using interrupted 4-0 polyglactin sutures. The primary outcome measures were postoperative tongue complications including hemorrhage，hematoma，and infection（Clavien-Dindo classification）. Secondary outcomes included VAS pain scores，functional recovery（difficulty drinking，difficulty eating，speech impairment，limited mouth opening），and sensory recovery（sensory disturbance，taste disturbance）. Results:The follow-up period ranged from 6 to 24 months，with a mean of 9.2 months. The 6-month follow-up rate was 100%. No Clavien-Dindo grade Ⅲ or higher complications（hemorrhage，hematoma，infection）occurred by the end of follow-up. Regarding secondary outcomes，the VAS pain score on postoperative day 1 was significantly better in the ADM group than in the suture group［0（0，3）vs. 2（0，3），P=0.013］.Functional impact：The incidence of difficulty drinking［24 cases（42.9%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 21 cases（42.0%）］，difficulty eating［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］，and speech impairment［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］on postoperative day 1，day 7，and within the first month，respectively，was significantly lower in the ADM group（all P<0.05）. On postoperative day 1 and day 7，the incidence of limited mouth opening was higher in the ADM group［0 cases vs. 6 cases（12.0%），0 cases vs. 6 cases（12.0%）］（ P<0.05）.Sensory recovery：The incidence of taste disturbance was higher in the ADM group at 7 days［8 cases（14.3%）vs. 0 cases］，1 month［8 cases（14.3%）vs. 0 cases］，and 3 months［8 cases（14.3%）vs. 0 cases］postoperatively（ P<0.05）. The incidence of sensory disturbance was higher in the ADM group at 1 day［20 cases（35.7%）vs. 6 cases（12.0%）］，7 days［16 cases（28.6%）vs. 6 cases（12.0%）］，and 1 month［16 cases（28.6%）vs. 6 cases（12.0%）］postoperatively（ P<0.05）. Pain scores and complication rates were zero in both groups after 6 months. Conclusions:ADM repair improves early recovery but may increase transient sensory complications. Both methods are safe for clinical application.

[Objective]To summarize Professor SHU Qijin's clinical experience in the diagnosis and treatment of palpitations induced by antitumor therapy.[Methods]Through outpatient apprenticeship,it systematically collected and analyzed clinical cases in which Professor SHU managed palpitations induced by antitumor therapies.Relevant classical treatises on traditional Chinese medicine(TCM)and modern literature were reviewed to summarize Professor SHU's understanding of the etiology and pathogenesis,characteristics of syndrome differentiation and treatment,as well as the composition,compatibility principles and clinical application of commonly used formulas.One representative medical case was selected for in-depth analysis as supporting evidence.[Results]Professor SHU believes that the pathogenesis of palpitations induced by antitumor therapy is primarily based on Qi and Yin deficiency.Therefore,the therapeutic approach emphasizes replenishing Qi and nourishing Yin as the foundation,with an additional focus on nourishing the heart meridian.Modified Shengmai Drink is commonly prescribed and adjusted according to the patient's condition.Holistic strategies are adopted to harmonize both the body and the mind,attending to both the physical form and spirit,while balancing warming and cooling interventions to regulate Yin and Yang.The TCM pattern diagnosis of the cited case was palpitation,with Qi and Yin deficiency as the root cause,and blood stasis and phlegm-dampness as the secondary symptoms,combined with Yang deficiency.It was treated by modified Shengmai Drink to benefit Qi and nourish Yin,with favorable therapeutic outcomes.[Conclusion]Professor SHU's clinical practice in managing palpitations induced by antitumor therapies emphasizes deficiency of both Qi and Yin as the fundamental pathogenesis.He advocates a comprehensive treatment principle that integrates replenishing Qi and nourishing Yin,harmonizing the body and mind,and employing both warming and cooling strategies according to clinical presentation.Professor SHU attaches great importance to clinical flexibility and individualized treatment adjustments,demonstrating rich clinical experience and remarkable therapeutic efficacy,which provide valuable guidance for wider clinical application.