As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

ObjectiveTo investigate the mechanism of action of remifentanil （RMZL） in alleviating lung ischemia-reperfusion injury （LIRI） in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α （HIF-1α）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. MethodsRats were stochastically assigned into Control group， LIRI group， RMZL low-dose group， RMZL medium-dose group， RMZL high-dose group， and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine （DMOG） group， with 18 rats in each group. Rats in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group， LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model； rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum； rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluorescence intensity of gasdermin D （GSDMD） and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α， NLRP3， cysteine-aspartic protease-1 （Cleaved caspase-1）， and gasdermin D-N （GSDMD-N） proteins in lung tissue. ResultsCompared to the Control group， the LIRI group showed disordered alveolar structure， thickened alveolar septa， and abundant inflammatory cell infiltration in rats. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins increased （P0.05）. For the LIRI group， rats in the RMZL low， medium， and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins declined， and the RMZL high-dose group showed the most prominent trend （P0.05）. Compared with the RMZL high-dose group， rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration， along with increased lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， levels of IL-1β and IL-18， and protein expression of HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N （P0.05）. ConclusionRMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

ObjectiveTo observe the clinical efficacy and safety of Yanghe Xiaonang Decoction （阳和消囊汤， YXD） in the treatment of polycystic ovarian syndrome （PCOS）-related infertility with healthy qi deficiency and phlegm stasis syndrome. MethodsA total of 120 PCOS-related infertility participants with healthy qi deficiency and phlegm stasis syndrome were randomly divided into a treatment group and a control group in a 1∶1 ratio， with 60 cases in each group. The treatment group started taking YXD on the first day of the menstrual cycle， one dose daily， until the day of sexual intercourse when follicles matured and were released. Those without mature follicles or ovulation could take it until the 14th to 28th day. The control group was given oral letrozole at 2.5 mg daily starting on the 5th day of the menstrual cycle for 5 consecutive days. If the basal body temperature curve remained monophasic on the 28th day of the menstrual cycle， and no dominant follicle was detected by color Doppler ultrasound， estrogen plus progesterone or progesterone alone was administered for withdrawal bleeding， followed by a new treatment cycle. The treatment lasted for three consecutive menstrual cycles. Patients were followed up for 3 months upon confirmed pregnancy or after the completion of the 3rd treatment cycle. The clinical pregnancy rate， total effective rate， pregnancy rate， biochemical pregnancy rate， embryonic arrest rate， and ectopic pregnancy rate between the two groups were compared. Transvaginal color Doppler ultrasound was used for monitoring endometrial thickness， cyclic ovulation status， number of follicles between 2-9 mm， and the difference in transverse and longitudinal diameters of dominant follicles. The levels of endocrine hormone indicators including serum testosterone （T）， prolactin （PRL）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， progesterone （P）， estradiol （E₂）， free testosterone （F-T）， androstenedione （ASD）， inhibin B （INH-B）， and anti-Müllerian hormone （AMH）， as well as the total traditional Chinese medicine （TCM） symptom scores before and after treatment were compared between the two groups. ResultsA total of 58 patients in each group were included in the statistical analysis. The clinical pregnancy rate in the treatment group was 39.66% （23/58）， higher than 22.41% （13/58） in the control group （P＜0.05）. The total effective rate in the treatment group was 96.55% （56/58）， higher than 79.31% （46/58） in the control group （P＜0.05）. The biochemical pregnancy rate and embryonic arrest rate in the treatment group were lower than those in the control group （P＜0.05）. The treatment group was superior to the control group in increasing endometrial thickness and reducing the number of 2-9 mm follicles at the 2nd and 3rd cycles， as well as in improving the cyclic ovulation status and the difference in transverse and longitudinal diameters of dominant follicles at the 3rd cycle （P＜0.05）. After treatment， the treatment group exhibited significant reductions in serum T， LH， F-T， ASD， INH-B， and AMH levels （P＜0.05）. The control group also showed significant decreases in LH， F-T， INH-B， and AMH levels （P＜0.05）. The levels of F-T， INH-B， and AMH in the treatment group after treatment were lower than those in the control group （P＜0.05）. The improvement of the total TCM symptom score in the treatment group was superior to that in the control group （P＜0.05）. ConclusionYXD can significantly improve the clinical pregnancy rate， reduce the rates of biochemical pregnancy and embryonic arrest， alleviate clinical symptoms， increase endometrial thickness， enhance dominant follicles， and improve endocrine hormone levels in PCOS-related infertility with healthy qi deficiency and phlegm stasis syndrome， showing good safety.

ObjectiveTo develop and evaluate an O-RADSbased multiparametric model integratingcontrast-enhanced US （CEUS） and the z-score standardized risk of ovarian malignancy algorithm （ROMA z-score） to improve the diagnostic accuracy for differentiating benign， borderline， and malignant ovarian epithelial tumors （OETs）. MethodsThis retrospective study included 129 patients with pathologically confirmed OETs between May 2018 and December 2024. Clinical variables （age， menopausal status， BMI， HE4， CA125） and sonographic features （conventional US and CEUS） were collected. Tumors were classified as benign， borderline， or malignant according to pathological findings. A random forest algorithm was used to contruct the predictive model. Receiver operating characteristic （ROC） curves were generated tocompare the diagnostic performance of O-RADS， O-RADS+CEUS， O-RADS+ROMA z-score， and O-RADS+ CEUS+ROMA z-score. ResultsAmong the 129 patients， 63 had benign tumors， 25 had borderline tumors， and 41 had malignant tumors. Compared with O-RADS alone， the combined O-RADS+CEUS+ROMA z-score model demonstrated superior diagnostic performance， with an AUC of 0.87 （95% CI： 0.79-0.95） vs. 0.64 （95% CI： 0.51-0.76）， P＜0.001， for differentiating benign from borderline tumors， and 0.90 （95% CI： 0.83-0.97） vs. 0.64 （95% CI： 0.50-0.78）， P＜0.001， for differentiating borderline from malignant tumors. The random forest analysis identified HE4， CA125 and CEUS features as the most important predictors，contributing 11.02， 8.82， 18.1 points， respectively， to the total importance score of 51.94. In the test cohort， the model achieved an overall diagnostic accuracy of 72.97%， with an AUC of 0.89（95%CI：0.77-1.00）， sensitivity of 67.06%， and specificity of 85.01%. ConclusionsO-RADS+CEUS+ROMA z-score multiparametric model demonstrated the highest diagnostic performance for in differentiating benign from borderline and borderline from malignant OETs. HE4， CA125 and CEUS features were identified as key predictive risk factors， supporting the role of this model in improving preoperative risk stratification of OETs.

Objective To explore the safety and efficacy of thoracoscopy-guided thoracic paravertebral block (TPVB) in thoracoscopic pulmonary resection, and to provide strategies for enhanced recovery after surgery (ERAS) in thoracoscopic lung resection. Methods Patients who underwent thoracoscopic pulmonary resection (including sublobar resection and lobectomy) in the 987th Hospital of Joint Logistics Support Force of People's Liberation Army, General Hospital of Central Theater Command of the People’s Liberation Army, and the First Affiliated Hospital with Nanjing Medical University between May 2021 and June 2023 were prospectively enrolled. The patients were randomly allocated into three groups in a single-blind manner using a random number table. Group A (incisional nerve block group) received a subcutaneous injection of ropivacaine (0.375%, 2 mg/kg) around the incision during chest closure. Group B (ultrasound-guided TPVB group) received an ultrasound-guided injection of ropivacaine (0.375%, 2 mg/kg) at the paravertebral space after chest closure. Group C (thoracoscopy-guided TPVB group) received a thoracoscopy-guided intrathoracic injection of ropivacaine (0.375%, 2 mg/kg) at the paravertebral space during chest closure. Perioperative adverse drug reactions, pain scores, postoperative analgesic consumption, and postoperative length of hospital stay were compared among the three groups. Results A total of 180 patients were included, comprising 108 females and 72 males, with a mean age of (62.15±7.36) years. There were no statistical differences among the three groups in baseline characteristics, including age, weight, gender, prevalence of comorbidities, operative time, number of surgical incisions, number of chest tubes, or intraoperative dosages of sufentanil and propofol (P>0.05). No adverse anesthesia events occurred during surgery in any of the groups. The pressing frequency of the patient-controlled intravenous analgesia (PCIA) pump, Visual Analogue Scale (VAS) pain scores, the rate of postoperative rescue analgesic use, and the incidences of postoperative cough and dizziness in the group C were significantly lower than those in the other two groups (P<0.05). The postoperative length of hospital stay in the group B and group C was significantly shorter than that in the group A (P<0.05). Conclusion Thoracoscopy-guided TPVB during chest closure can effectively alleviate postoperative pain without increasing postoperative side effects, which facilitates the enhanced recovery after thoracoscopic lung surgery.

Objective: To analyze the mediating effects of self-efficacy and self-management behaviors on the relationship between depression symptoms and glycemic control among elderly patients with type 2 diabetes mellitus (T2DM), so as to provide references for optimizing health management of elderly T2DM patients. Methods: T2DM patients aged ≥60 years from 8 community health service centers in Nanjing City were selected using a convenience sampling method. Basic information such as gender and age was collected through questionnaires. Depressive symptoms, self-efficacy, and self-management behaviors were assessed using the Patient Health Questionnaire, the Diabetes Self-Efficacy Scale, and the Diabetes Self-Management Behavior Scale, respectively. Glycated hemoglobin (HbA1c) was measured to evaluate glycemic control. A mediating effect model was constructed to analyze the mediating effects of self-efficacy and self-management behaviors on the relationship between depressive symptoms and glycemic control. Results: A total of 567 elderly T2DM patients were included, with a median age of 70.00 (interquartile range, 7.50) years. There were 248 males (43.74%) and 319 females (56.26%). The median scores of self-efficacy, self-management behaviors, depressive symptoms, and HbA1c were 3.89 (interquartile range, 0.78), 4.45 (interquartile range, 1.55), 4.00 (interquartile range, 6.00), and 6.80% (interquartile range, 1.40%), respectively. The mediating effect analysis showed that depressive symptoms indirectly affected glycemic control among elderly T2DM patients through the independent mediating effects of self-efficacy (β=0.028, 95%CI: 0.016-0.043) and self-management behaviors (β=0.009, 95%CI: 0.003-0.016), as well as the chain mediating effect of both (β=0.025, 95%CI: 0.017-0.035). The mediating effects of self-efficacy and self-management behaviors accounted for 36.66% and 11.35% of the total effect, respectively, while the chain mediating effect accounted for 32.15% of the total effect. Conclusion Self-efficacy and self-management behaviors play mediating roles in the relationship between depressive symptoms and glycemic control among elderly T2DM patients.

AIM:To evaluate the effectiveness of EYESI binocular indirect ophthalmoscope simulation system as a training platform for fundus examination skills of general practitioner.METHODS:Prospective randomized study. A total of 40 general practitioners who received clinical ophthalmology training at Shenzhen Eye Hospital from January 2021 to December 2024 were selected and randomly divided into two groups by random number table method, with 20 cases in the study group and 20 cases in the control group. The study group was trained by EYESI binocular indirect ophthalmoscope simulation system and the control group was trained by conventional teaching. Training effects of the two groups were analyzed.RESULTS: The general information of the two groups was comparable. Through training with the EYESI binocular indirect ophthalmoscope simulator, the study group showed significant improvements in total examination and drawing scores compared to pre-training results(all P<0.001). Additionally, examination duration, retinal light exposure time, and drawing time were all significantly shorter than those before training(all P<0.001).The study group achieved significantly higher total examination and drawing scores than the control group during the EYESI binocular indirect ophthalmoscope simulator assessment(all P<0.001). Furthermore, examination duration, retinal light exposure time, and drawing time were all significantly shorter in the study group compared to the control group(all P<0.001). Moreover, ratings for the novelty of the training method and overall satisfaction with the training were significantly higher in the study group than in the control group(all P<0.001); while the perceived psychological stress during training was significantly lower in the study group(P<0.001).CONCLUSION:The EYESI binocular indirect ophthalmoscope simulaton system effectively enhances both the proficiency in fundus examination skills and overall training satisfaction among general practitioners.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome