Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective: To analyze the prevalence and trend of screening myopia among primary and middle school students in Linfen Community of Shanghai from 2019 to 2023, so as to provide a reference for the prevention and control of myopia from the perspective of the community. Methods: From 2019 to 2023, all primary(5) and middle(2) school students aged 6-15 years in Linfen Community of Shanghai were screened. Statistical analysis was performed using the Chi square test and trend Chi square test. The curve fitting model was used to fit the model of the increase rate of screening myopia among primary and middle school students in 2019, 2021 and 2023. Results: The overall rate of screening myopia among primary and middle school students in Linfen community from 2019 to 2023 was 55.17%. The prevalence rate of screening myopia was 79.43% in boys and 81.92% in girls in middle school, and the difference was statistically significant ( χ 2=5.71, P =0.02). In 2019, 2021, and 2023, the peak age of screening myopia among primary and middle school students in Linfen Community gradually occurred earlier, at the age of 7(12.13%), 6( 12.28 %), and 6(14.99%) years old, respectively. The growth rate of screening myopia in students aged 8-12 years in 2023 was lower than that in 2019 and 2021. Conclusions The screening myopia rate of primary and middle school students aged 6-15 years in Linfen Community is relatively high, with primary school girls higher than boys, and growth spurt accelerates. It is suggested that prevention and control of myopia in the community should focus on preschool children and adolescent girls.

Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation.Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used,and data processing was performed using the Seurat package,with integrated data to remove batch effects.Cell subpopulations were annotated based on known markers.Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package,and inferred based on the expression of cell surface receptors and ligands.Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors.Finally,differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting.Results A total of 7 different cell subpopulations were found in mouse islets,with β-cells being the most abundant.Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest.Gene set enrichment analysis showed that after treatment with inflammatory factors,the immune response was positively enriched in β-cells,while peptide hormone metabolism,bile acid metabolism,and ion homeostasis were downregulated.The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1(EGR1),nuclear factor-κB inhibitor α(NFKBIA),and activating transcription factor 3(ATF3).Among them,NFKBIA and ATF3 were upregulated,while EGR1 was downregulated.The expression of EGR1 protein was downregulated after 24 h,48 h,and 72 h of cold ischemia.Conclusions EGR1 is a transcription factor closely related to islet cold ischemia,and future research should focus on the specific mechanisms of EGR1 and its downstream target genes,in order to provide more effective strategies for clinical treatment of islet transplantation.

Objective:To study the effects of periodontitis on bone and tryptophan metabolism of gut microbiota in the context of estrogen deficiency.Methods:Thirty-two female C57BL6/J mice were randomly divided into four groups based on table of random numbers ( n=8 in each group): Sham group, in which mice were given sham surgery; Sham_Lig group, in which mice were given sham surgery and were induced to periodontitis by ligating the bilateral maxillary second molars with 5-0 silk threads at the fourth week; Ovx group, in which mice were given bilateral ovariectomy; Ovx_Lig group, in which mice were given bilateral ovariectomy and were induced to periodontitis at the fourth week. After 8 weeks of ligation, the mice of 4 groups were euthanized for collecting the samples of femur, tibia, mandible and skull. Those samples were scanned by micro-CT to measure the bone mineral density (BMD), bone volume versus total volume ratio (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp). The cecum contents of 4 groups of mice were collected for gut microbiota 16S rRNA gene sequencing. The tryptophan and its metabolites in intestinal tracts were detected by liquid chromatography-mass spectrometry. Pearson correlation analysis was performed to analyze the correlation between the abundance of gut microbiota and the content of tryptophan and its metabolites. Results:Femur BMD [(82.23±3.97) mg/cm 3], BV/TV [(9.25±1.37)%] and Tb.Th [(70.95±5.70) μm] in Ovx_Lig group were significantly lower than Ovx group [(96.30±3.76) mg/cm 3 ( P=0.004); (14.45±1.55)% ( P=0.022) and (87.58±8.02) μm ( P<0.001), respectively]. The β-diversity analysis of gut microbiota based on Bray-Curtis distance showed that samples of Ovx_Lig group and Ovx group were obviously grouped. Linear discriminant analysis effect size (LEfSe) showed that Alistipes was the representative genus in Ovx_Lig group. The relative abundance of Alistipes in Ovx_Lig group [(0.42±0.14)%] were significantly higher than that in Ovx group [(0.17±0.05)%] ( t=4.45, P<0.001). Tryptophan metabolism analysis showed that the content of kynurenic acid [(531.12±158.60) ng/g] in Ovx_Lig group were significantly higher than that in Ovx group [(400.42±57.96) ng/g] ( t=2.19, P=0.046). And the content of indole-3-carbaldehyde [(383.37±144.06) ng/g] in Ovx_Lig group were significantly lower than Ovx group [(701.72±141.93) ng/g] ( t=4.45, P<0.001). Correlation analysis showed that relative abundance of Alistipes was positively correlated with kynurenic acid ( r=0.32, P=0.088), while negatively correlated with indole-3-carbaldehyde ( r=-0.32, P=0.088). Conclusions:Periodontitis can induce bone destruction of femur in estrogen-deficient mice, the mechanism of which may be related to Alistipes in gut and the tryptophan metabolites kynurenic acid and indole-3-carbaldehyde.

Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

Objective To observe the effect of exsanguination at jing points and auricular tips on antipyretic effect and inflammation factors level in patients with fever caused by coronavirus disease 2019(COVID-19).Methods A retrospective study was conducted.A total of 521 febrile patients with COVID-19 admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from January 1 to 10,2023 were selected as the study subjects.The patients were divided into the control group(treated with conventional treatment)and the experimental group(treated with exsanguination of jing points and auricular tips based on the control group)according to whether they received traditional Chinese medicine(TCM)exsanguination treatment.The body temperature before treatment and 30 minutes and 4 hours,24 hours after treatment,the immediate(within 30 minutes)antipyrexia efficiency,the time of body temperature returning to normal,and the levels of inflammatory factors before treatment and 48 hours after treatment were collected,and the differences between the two groups were compared.According to the standard of fever relief≥1℃within 4 hours,the differences of the average onset time of fever and the rate of fever relief at 2.5,3 and 4 hours after treatment were compared between the two groups.Kaplan-Meier curve was drawn to analyze the change of 4-hour antipyrexia rate in the two groups before and after matching.Results A total of 169 cases in the experimental group and 352 cases in the control group were finally included.Because this study was retrospective,there were significant differences in the course of disease and underlying diseases(chronic bronchitis,diabetes,renal insufficiency,hepatobiliary diseases)between the two groups at baseline(all P＜0.05).In order to reduce the differences,the above 4 factors were included in the predictor variables,and a 1∶1 propensity matching was performed to match 166 pairs of case samples,which were comparable.The result showed body temperature of the two groups gradually decreased with the extension of time,and the body temperature of the experimental group was significantly lower than that of the control group at each time point(℃:30 minutes was 38.32±0.22 vs.38.43±0.24,4 hours was 37.67±0.32 vs.38.13±0.51,24 hours was 37.03±0.38 vs.37.14±0.51,all P＜0.05),the immediate antipyrexia efficiency was significantly higher than that of the control time group[63.86%(106/166)vs.44.58%(74/166),P＜0.05],and the time of body temperature recovery to normal was significantly shorter than that of the control group(hours:19.25±7.79 vs.38.90±17.17,P＜0.05).In terms of the 4 hours antipyretic onset dynamic time,the average antipyretic onset time of the experimental group was significantly shorter than that of the control group[hours:4.39(4.11,4.68)vs.7.16(6.71,7.61),P＜0.05],the fever relief rates at 2.5,3 and 4 hours were significantly higher than those in the control group[6.63%(11/166)vs.0.60%(1/166),24.10%(40/166)vs.4.82%(8/166),74.10%(123/166)vs.38.55%(64/166),respectively,all P＜0.05].Kaplan-Meier curve analysis showed that there were statistically significant differences in 4 hours fever reduction rates between the two groups before and after matching(all P＜0.05).In terms of inflammatory factors,high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the two groups after treatment were significantly lower than those before treatment[hs-CRP(mg/L):control group was 32.03±15.38 vs.79.78±13.34,experimental group was 33.21±16.07 vs.80.03±14.66;TNF-α(μg/L):control group 2.91±0.88 vs.5.09±0.95,experimental group 2.83±0.98 vs.5.10±0.87;IL-6(ng/L):control group was 96.30±48.12 vs.206.48±56.70,experimental group was 94.01±45.13 vs.202.38±55.38,all P＜0.05],but there was no significant difference in the levels of the above indicators between the two groups after treatment.Conclusion Exsanguination at the jing points and auricular tips has a good antipyretic effect in the treatment of fever caused by COVID-19,which can accelerate the antipyretic time,improve the antipyretic efficiency,and reduce the level of inflammatory factors.

This review summarized the latest advances in islet transplantation, islet encapsulation and co-delivery strategies of cell and growth factors.

Surgery is a classic traditional method for the treatment of early-stage esophageal cancer, and it is also recognized as an effective first-choice method in the medical community. With the development of endoscopic technology, esophagus-preserving comprehensive treatment of esophageal cancer has almost the same or even better effects in some aspects in the treatment of early esophageal cancer than surgery. Many clinical guidelines have also recommended it as the first-choice treatment for early esophageal cancer. The room for surgical treatment of esophageal cancer has been further compressed. This article discusses the comprehensive treatment model of esophageal cancer from the perspective of thoracic surgery, aiming to find a new position of thoracic surgery in the treatment of esophageal cancer.

Objective:To report the surgical techniques and clinical outcomes of multi-dimensional fixation of patellar multi-fragmentary fractures with locking plates.Methods:A retrospective study was performed in the 26 patients with patellar multi-fragmentary fracture who had undergone open reduction and 3-D internal fixation with locking plates from November 2016 to July 2020 at Department of Orthopaedic Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University. There were 17 males and 9 females, with an average age of 62.6 years (from 31 to 90 years). The patellar fractures were exposed and reduced via the longitudinal anterior midline incision of the knee. After the reduction was initially maintained with a cerclage wire, a trimmed and pre-contoured 3.5 mm locking plate was applied onto the patellar surface. After-wards, locking screws were inserted from the lower pole to the upper pole of the patella, from the anterior to the posterior and from the lateral to the medial, respectively, to complete the multi-planar fixation. Follow-ups assessed the B?stman score, knee pain visual analogue scale (VAS), radiographic image and fracture healing, range of motion of the knee, and complications.Results:All the 26 patients were followed up for 12 to 56 months (average, 28 months). Crutches were used while walking until an average of 1.6 months (from 1 to 3 months) after operation in all patients. At the last follow-up, the B?stman score averaged 27.5 points (from 17 to 30 points), yielding 12 excellent, 13 good and 1 poor case with an excellent to good rate of 96.2% (25/26); the knee pain VAS averaged 1.2 points (from 0 to 5 points); the active knee flexion averaged 125° (from 100° to 150°). No breakage, loosening or displacement of the patellar plates or screws was observed during follow-up, but cerclage wire breakage occurred without any symptom in 11 cases. Four patients complained of hardware irritation, and 4 patients underwent hardware removal after fracture union.Conclusion:Multi-dimensional fixation with locking plates is a viable and safe surgical option for patellar multi-fragmentary fractures, due to its satisfactory therapeutic outcomes.