The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Objective:To compare the clinical efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma.Methods:A prospective, randomized, controlled study was conducted. Patients with melasma were collected from the Department of Dermatology, Guangzhou Dermatology Hospital from March 2023 to May 2024, and divided into a nanomicroneedle group (receiving nanomicroneedle-mediated delivery of tranexamic acid) and an ultrasound group (receiving ultrasound-mediated delivery of tranexamic acid) using the random number table method. Both groups underwent the treatment once a week for a total of 8 sessions. At week 12, outcomes including melasma area and severity index (MASI) scores, treatment response rates, VISIA brown spot scores, pain scores, and adverse reactions were evaluated and compared between the two groups. Statistical analyses were carried out using two-independent-sample t test, Mann-Whitney U test, and chi-square test. Results:A total of 80 patients with melasma were included, with 40 in each group. In the nanomicroneedle group, the patients were aged 40.35 ± 7.39 years (range: 25 - 55 years), with the disease duration being 8.45 ± 4.77 months (range: 1 - 16 months) ; in the ultrasound group, the patients were aged 40.25 ± 7.76 years (range: 25 - 55 years), and their disease duration was 10.45 ± 5.07 months (range: 2 - 17 months) ; there were no significant differences in ages or disease duration between the two groups (both P > 0.05). At week 12, both groups demonstrated reduced MASI scores compared to baseline scores, and the MASI scores were significantly lower in the nanomicroneedle group ( M[ Q1, Q3]: 5.80[4.20, 9.35]) than in the ultrasound group (8.65[5.70, 10.80], Z = 2.50, P = 0.012). The overall response rate was significantly higher in the nanomicroneedle group (97.5%, 39/40) than in the ultrasound group (55.0%, 22/40; χ2 = 19.95, P < 0.001). The lateral facial VISIA brown spot scores were also significantly lower in the nanomicroneedle group (left side: 126.18 ± 36.54 points; right side: 138.50 ± 40.76 points) than in the ultrasound group (left side: 142.37 ± 32.40 points; right side: 157.13 ± 39.59 points; t = -2.10, -2.07, P = 0.039, 0.041, respectively). In the nanomicroneedle group, the pain scores were 4.12 ± 1.47 points, and varying severity of adverse reactions such as erythema, edema and dryness occurred after operation, all of which resolved spontaneously within 48 hours. No marked adverse reactions were observed in the ultrasound group. Conclusion:Nanomicroneedle-mediated delivery of tranexamic acid demonstrated superior clinical efficacy and favorable safety profiles compared to the ultrasound-mediated delivery, providing more options for the treatment of melasma.

Depression is a highly heterogeneous psychiatric disorder with complex pathogenesis influenced by the interplay of biological,psychological,and social-environmental factors.Based on the 2021 edition of the Chinese Guidelines for the Prevention and Treatment of Depressive Disorders,which explicitly identify gender as a significant risk factor for depression onset,this paper systematically reviews the gender-differentiated pathogenesis and therapeutic advances in depression from both traditional Chinese medicine(TCM)and Western medical perspectives.In Western medicine,a large number of studies have demonstrated the sex-specific mechanism of estrogen/testosterone fluctuations and monoamine transmitter system regulation.While in TCM,although the constitution theory proposes that there are significant gender differences in congenital constitution and that qi depression and qi deficiency are associated with susceptibility to depression,current evidence primarily relies on cross-sectional surveys and lacks validation through high-quality RCTs.Compared with Western medicine,the direct research on gender-differentiated antidepressant effects in TCM remains relatively underdeveloped.In future study,it may be possible to deepen and improve the research on anti-depression in TCM from the biological markers of particular constitutions in the gender dimension.This paper advocates establishing a bio-psycho-social integrated intervention model,advancing mechanistic exploration through prospective cohort studies and multi-omics technologies,and promoting precision diagnosis and treatment systems based on gender differences,and to form a three-dimensional diagnosis and treatment and research system that covers biomarkers,social role assessment,and TCM constitution identification,in order to provide a new theoretical framework and a practical pathway for the precise medical treatment of depression.

Objective:To analyze the characteristics of Fournier gangrene (FG) induced by sodium-glucose cotransporter 2 inhibitors (SGLT2i), and provide reference for clinical safe drug use.Methods:CNKI, Wanfang Med Online, VIP, PubMed, Web of Science and other databases (up to January 2024) were retrieved and clinical data on patients with FG associated with the 5 kinds of SGLT2i currently used in clinical practice in China were collected and descriptively analyzed, including gender, age, comorbidities, concomitant medications, onset time and clinical manifestations of SGLT2i-related FG, laboratory and imaging examination results, treatment and outcomes, etc.Results:A total of 15 documents were included in the analysis, involving 15 patients, with 12 males and 3 females. The age of these patients ranged from 34 to 72 years, with 11 cases being over 50 years. Dapagliflozin was used in 7 cases, empagliflozin in 6 cases, canagliflozin in 2 cases, and no related reports on ertugliflozin and henagliflozin were collected. The main clinical manifestations of the 15 patients were redness, swelling, pain, abscess or purulent discharge in perineum, scrotum and perianal, etc. The time from application of SGLT2i to onset of FG ranged from 1 month to 6 years. Wound secretion bacterial culture was performed in 10 patients, and the results were all positive, including 9 cases of bacterial infection and 1 case of mixed infection of bacteria and fungi. All 13 patients who underwent imaging examinations had imaging manifestations related to FG. SGLT2i were discontinued in all patients. After treatments with broad-spectrum antibiotics and surgery, 14 cases were improved and 1 case was cured.Conclusions:SGLT2i has the risk of causing FG, which is more common in males. The clinical use of SGLT2i should be monitored closely. Secretion culture and imaging examination are helpful for the diagnosis of FG. The patient′s prognosis is good after discontinuation of medication, symptomatic treatment, and surgery.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To introduce the concepts and principles of the win ratio method and to analyze it in the context of a case study of a clinical trial in cerebrovascular disease.Methods Based on the study of clopidogrel with aspirin in high risk patients with acute non disabling cerebrovascular events 2,and key prognostic factors,the outcome events were defined sequentially as ① time to death within 90 d,② time to recurrence of ischemic stroke within 90 d,③ time to moderate-to-severe hemorrhage within 90 d.Using clopidogrel combined with aspirin as the reference group,the winning ratio(Rw)of ticagrelor combined with aspirin was analyzed by the win ratio method,and the 95% confidence interval(CI)of Rw was estimated by the Bootstrap method and compared with the hazard ratio(HR)calculated by the competing risk model.Results When only fatal events were considered,the win ratio method suggested that the ticagrelor group was significantly better than the clopidogrel group,Rw=2.00(95% CI:1.52-2.47),and after stepwise inclusion of ischemic stroke and moderate-to-severe hemorrhage recurrence,the win ratio method yielded a value of 1.29(95% CI:1.25-1.57),and the HR value from Fine and Gray competing risk regression was 0.78(95% CI:0.65-0.95),both of which indicated that the efficacy of the ticagrelor group was superior to that of the clopidogrel group.Conclusion The win ratio method can be used to analyze clinical trials with composite endpoints after prioritizing multiple outcome variables,showing the advantages of win ratio and its promising application in cerebrovascular disease research.

Acute ischemic stroke(AIS)is associated with high mortality and disability rates,presenting a substantial challenge to global public health challenge.Intravenous thrombolysis(IVT)is recognized as a cornerstone of early AIS treatment and is recommended as the standard therapeutic approach by both national and international guidelines.However,the clinical efficacy of IVT remains suboptimal due to several limitations,including a narrow therapeutic time window and the inevitable activation of the coagulation system and platelet aggregagation during thrombolysis.These factors may contribute to adverse outcomes such as early neurological deterioration(END)and vascular re-occlusion.Antiplatelet therapy(APT),which inhibits platelet aggregations,reduces microthrombus formation,and stabilizes the vascular endothelium with multifaceted mechanisms,has emerged as a promising adjunctive strategy to IVT,offering potential synergistic effects.This review summarized the latest evidence from both domestic and international studies,focusing on the mechanisms of APT,recent clinical advancements in IVT combined with APT,and the safety and efficacy of APT administration at different time windows relative to IVT.Emphasis is placed on the influence of various antiplatelet agents,dosing regimens,and initiation timing on therapeutic outcomes,alongside a comprehensive evaluation in the context of current guideline recommendations and clinical practice.Current guidelines recommend initiating APT 24 h after IVT,following imaging confirmation to exclude the risk of intracranial hemorrhage.However,the efficacy and safety of earlier APT initiation remain inconclusive.Individualized treatment strategies,such as early administration of low-dose,short-acting APT or combination therapy in specific patient subgroups,may effectively balance therapeutic benefits and risks.The adjunctive use of APT in IVT holds promise for enhancing efficacy and improving clinical outcomes,but precise stratification of safety and efficacy is essential.Future research should focus on optimizing combination IVT and APT strategies through individualized patient profiling,appropriate drug selection,and dynamic imaging monitoring to achieve precision management in AIS treatment.

The"promising zone"is a method used to analyze interim data from adaptive design clinical trials in an unblinded state.It allows for the adjustment of sample size based on interim results to enhance the trial's probability of success or minimize investment in unnecessary sample size.Mehta and Pocock proposed rules for increasing sample size based on interim analysis results using the concept of the"promising zone"(MP design).Furthermore,combination of the MP design with group sequential design can set up early stopping boundaries in trials,allowing for a reduction in sample size under favorable or unfavorable zone.The combination test(CT)design further optimizes the framework of the"promising zone",by considering sample size and conditional power in combination to achieve the highest conditional power with the smallest sample size.This review summarizes the principles of the"promising zone",introduces the method of determining the"promising zone"and re-estimating sample size,and further illustrates the feasibility of this method in clinical trials with a practical case.

Objective To introduce the concepts and principles of the win ratio method and to analyze it in the context of a case study of a clinical trial in cerebrovascular disease.Methods Based on the study of clopidogrel with aspirin in high risk patients with acute non disabling cerebrovascular events 2,and key prognostic factors,the outcome events were defined sequentially as ① time to death within 90 d,② time to recurrence of ischemic stroke within 90 d,③ time to moderate-to-severe hemorrhage within 90 d.Using clopidogrel combined with aspirin as the reference group,the winning ratio(Rw)of ticagrelor combined with aspirin was analyzed by the win ratio method,and the 95% confidence interval(CI)of Rw was estimated by the Bootstrap method and compared with the hazard ratio(HR)calculated by the competing risk model.Results When only fatal events were considered,the win ratio method suggested that the ticagrelor group was significantly better than the clopidogrel group,Rw=2.00(95% CI:1.52-2.47),and after stepwise inclusion of ischemic stroke and moderate-to-severe hemorrhage recurrence,the win ratio method yielded a value of 1.29(95% CI:1.25-1.57),and the HR value from Fine and Gray competing risk regression was 0.78(95% CI:0.65-0.95),both of which indicated that the efficacy of the ticagrelor group was superior to that of the clopidogrel group.Conclusion The win ratio method can be used to analyze clinical trials with composite endpoints after prioritizing multiple outcome variables,showing the advantages of win ratio and its promising application in cerebrovascular disease research.

Acute ischemic stroke(AIS)is associated with high mortality and disability rates,presenting a substantial challenge to global public health challenge.Intravenous thrombolysis(IVT)is recognized as a cornerstone of early AIS treatment and is recommended as the standard therapeutic approach by both national and international guidelines.However,the clinical efficacy of IVT remains suboptimal due to several limitations,including a narrow therapeutic time window and the inevitable activation of the coagulation system and platelet aggregagation during thrombolysis.These factors may contribute to adverse outcomes such as early neurological deterioration(END)and vascular re-occlusion.Antiplatelet therapy(APT),which inhibits platelet aggregations,reduces microthrombus formation,and stabilizes the vascular endothelium with multifaceted mechanisms,has emerged as a promising adjunctive strategy to IVT,offering potential synergistic effects.This review summarized the latest evidence from both domestic and international studies,focusing on the mechanisms of APT,recent clinical advancements in IVT combined with APT,and the safety and efficacy of APT administration at different time windows relative to IVT.Emphasis is placed on the influence of various antiplatelet agents,dosing regimens,and initiation timing on therapeutic outcomes,alongside a comprehensive evaluation in the context of current guideline recommendations and clinical practice.Current guidelines recommend initiating APT 24 h after IVT,following imaging confirmation to exclude the risk of intracranial hemorrhage.However,the efficacy and safety of earlier APT initiation remain inconclusive.Individualized treatment strategies,such as early administration of low-dose,short-acting APT or combination therapy in specific patient subgroups,may effectively balance therapeutic benefits and risks.The adjunctive use of APT in IVT holds promise for enhancing efficacy and improving clinical outcomes,but precise stratification of safety and efficacy is essential.Future research should focus on optimizing combination IVT and APT strategies through individualized patient profiling,appropriate drug selection,and dynamic imaging monitoring to achieve precision management in AIS treatment.