Interplay between the ß-lactam side chain and an active-site mobile loop of NDM-1 in penicillin hydrolysis as a potential target for mechanism-based inhibitor design.

Metallo-ß-lactamases (MßLs) stand as significant resistant mechanism against ß-lactam antibiotics in Gram-negative bacteria. The worldwide dissemination of New Delhi metallo-ß-lactamases (NDMs) intensifies antimicrobial resistance, posing severe threats to human health due to the absence of inhibitors available in clinical therapy. L3, a flexible ß-hairpin loop flanking the active site in MßLs, has been proven to wield influence over the reaction process by assuming a crucial role in substrate recognition and intermediate stabilization. In principle, it potentially retards product release from the enzyme, consequently reducing the overall turnover rate although the details regarding this aspect remain inadequately elucidated. In this study, we crystallized NDM-1 in complex with three penicillin substrates, conducted molecular dynamics simulations, and measured the steady-state kinetic parameters. These analyses consistently unveiled substantial disparities in their interactions with loop L3. We further synthesized a penicillin V derivative with increased hydrophobicity in the R1 side chain and co-crystallized it with NDM-1. Remarkably, this compound exhibited much stronger dynamic interplay with L3 during molecular dynamics simulation, showed much lower Km and kcat values, and demonstrated moderate inhibitory capacity to NDM-1 catalyzed meropenem hydrolysis. The data presented here may provide a strategic approach for designing mechanism-based MßL inhibitors focusing on structural elements external to the enzyme's active center.

Precision diagnosis and treatment of antibody-mediated rejection / 中华器官移植杂志

Based upon the underlying mechanism and pathological evidence of tissue injury of antibody-mediated rejection (AMR) , four etiological and symptomatic therapies were proposed for managing AMR, including etiological treatment of AMR including antibody-targeting, B cell or plasma cell-targeting therapies; strategies for preventing antibody-mediated endothelial damage: an inhibition of complement/antibody dependent cell-mediated pathways; anticoagulant & thrombolytic therapies for thrombotic microangiopathy secondary to endothelial damage ; anti-inflammatory therapies for acute/chronic vascular inflammation secondary to endothelial damage. Etiological treatment is essential for preventing and treating AMR while symptomatic measures, such as anticoagulant, thrombolytic and antiinflammatory therapies, are stressed. Finally the authors devised therapeutic strategies for AMR in 4 different patient groups of non-sensitized allograft recipients, sensitized allograft recipients, individuals with active AMR and those with chronic active AMR.

Self-management and family support among elderly patients with type 2 diabetes in community: based on semi-structured interviews / 中华全科医师杂志

Objective:To investigate the status of self-management and family support among elderly diabetic patients in community.Methods:Eight elderly patients with type 2 diabetes were interviewed in Xietu Community Health Service Center in Shanghai by semi-structured interviews from March 1st to March 15th, 2022. The interview outline focused on the impact of the disease on the patients' daily life, the status of disease self-management, and the support provided by their family. The contents of interviews were analyzed and extracted by Colaizz 7-step analysis method.Results:Of the 8 interviewees, there were 2 males and 6 females, aged (75.25±3.01)years old, with a disease course of (17.50±8.50)years. The interviews showed that there were three themes in the area of family support: difficulties in disease management (in terms of diet, exercise, medication, disease surveillance, health knowledge and quitting unhealthy habits), helpfulness of family support in management of above behaviors, differences between family support and support from others (including eating habits, information sharing, emotional support, patient trust, and continuity of support).Conclusions:The elderly diabetic patients in the community have some awareness of health management, but there is still much room for improvement. The supervision and support from family members can help patients improve their self-management and quality of life.

A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement / 罕见病研究

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement / 罕见病研究

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Application of seminar in addition to case-based learning in physical therapy practical teaching / 中国康复理论与实践

Objective To explore the effect of seminar based on case-based learning(CBL)in practical teaching of physical therapy. Methods From July,2021 to June,2022,42 rehabilitation therapy students for internships in Rehabilitation Medicine Center,the First Affiliated Hospital of Nanjing Medical University were non-directionally recruited,and random-ly divided into control group(n = 21)and experimental group(n = 21).The experimental group received instruc-tion using seminar and CBL,while the control group received CBL alone,for three months.The scores of theoret-ical and practical assessments were observed,and the satisfaction was investigated using a self-designed question-naire. Results The scores of both theoretical and practical assessments were better in the experimental group than in the control group(t>2.421,P<0.05);while the satisfaction was better in terms of motivating learning enthusiasm,enhanc-ing learning abilities,cultivating clinical reasoning skills,improving teacher-student communication,promoting teamwork,enhancing overall competence,and satisfying to the teaching in the experimental group than in the control group(χ2>6.667,P<0.05). Conclusion The combination of seminar with CBL would enhance the effect of practical teaching in physical therapy.

Physcion increases the sensitivity of hepatocellular carcinoma to sorafenib through miRNA-370/PIM1 axis-regulated glycolysis.

BACKGROUND: Resistance to sorafenib has become a challenge in clinical treatment of hepatocellular carcinoma (HCC). Physcion is a common bioactive anthraquinone that has potential as an anticancer agent. AIM: To study the effect of physcion on sensitizing HCC cells to sorafenib. METHODS: Sorafenib-resistant HCC cells were established and treated with sorafenib and/or physcion. The cell viability, proliferation and apoptosis were measured by cell counting kit-8, colony formation, flow cytometry, and in vivo xenograft model. Glucose uptake, lactate acid production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) were measured to analyze glycolysis. Expression of glycolysis-related regulators was assessed by western blotting. RESULTS: The addition of physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells, manifested by enhanced apoptosis and suppressed cell growth. The glucose uptake, lactate acid production, and ECAR were elevated, and OCR was suppressed by physcion treatment. The level of PIM1 was elevated and miR-370 was suppressed in sorafenib-resistant HCC cells compared with the parental cells, which was suppressed by physcion treatment. Inhibition of miR-370 notably reversed the effects of physcion on sorafenib-resistant HCC cells. CONCLUSION: Our data indicated that physcion enhanced the sensitivity of HCC cells to sorafenib by enhancing miR-370 to suppress PIM1-promoted glycolysis.

Progress in the research of cuproptosis and possible targets for cancer therapy.

Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment. According to a recently published study in Science, copper death (cuproptosis) occurs when intracellular copper is overloaded, triggering aggregation of lipidated mitochondrial proteins and Fe-S cluster proteins. This intriguing phenomenon is triggered by the instability of copper ions. Understanding the molecular mechanisms behind cuproptosis and its associated genes, as identified by Tsvetkov, including ferredoxin 1, lipoic acid synthase, lipoyltransferase 1, dihydrolipid amide dehydrogenase, dihydrolipoamide transacetylase, pyruvate dehydrogenase α1, pyruvate dehydrogenase ß, metallothionein, glutaminase, and cyclin-dependent kinase inhibitor 2A, may open new avenues for cancer therapy. Here, we provide a new understanding of the role of copper death and related genes in cancer.

Patients with epilepsy without cognitive impairment show altered brain networks in multiple frequency bands in an audiovisual integration task.

OBJECTIVES: Comorbid cognitive and behavioral deficits are often observed in patients with epilepsy. It is not clear whether the brain networks of patients with epilepsy without cognitive decline differs from that of healthy controls in different frequency bands in the task-state. The purpose of our study was to explore whether epilepsy affects the structure of brain networks associated with cognitive processing, even when patients with epilepsy do not have cognitive impairment. METHODS: We designed an audiovisual discrimination task and recorded electroencephalogram (EEG) data from healthy controls and patients with epilepsy. We established constructed time-varying brain networks across the delta, theta, alpha, and beta bands on the task-state EEG data during audiovisual integration processing. RESULTS: The results showed changes in the structure of the brain networks in the theta, alpha, and beta bands in patients with epilepsy who had no cognitive deficit. No significant difference in the connectivity strength, clustering coefficient, characteristic path length, or global efficiency was noted between patients and healthy controls. Moreover, the structure of brain networks in patients showed no correlation with the behavioral performance. CONCLUSION: The repeated abnormal firing of neurons in the brain of patients with epilepsy may inhibit it from optimizing networks into more efficient structures. Epilepsy might affect decision-making ability by damaging the neural activity in the beta band and preventing its correlation with decision-making behaviors.

Recent progress in understanding mitokines as diagnostic and therapeutic targets in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths. The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism, including mitochondrial stress response. Mitokines, soluble proteins produced and secreted in response to mitochondrial stress, play an essential immunomodulatory role. Immunotherapy has emerged as a crucial treatment option for HCC. However, a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment. Therefore, exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy. This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function. In addition, a systematic review of mitokines-mediated immunomodulation in HCC is presented. Finally, the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized. Recent progress in mitokine research represents a new prospect for mitochondrial therapy. Considering the potential of mitokines to regulate immune function, investigating them as a relevant molecular target holds great promise for the diagnosis and treatment of HCC.

Crystal structures and solution conformations of HtrA from Helicobacter pylori reveal pH-dependent oligomeric conversion and conformational rearrangements.

Helicobacter pylori is a Gram-negative microaerophilic bacterium that infects over 50 % of the world's population, making it a major risk factor for chronic gastritis, ulcer diseases of the stomach and duodenum, MALT lymphoma, and gastric cancer. The clinical consequences of H. pylori infection are closely linked with the expression of virulence factors secreted by the bacterium. One such virulence factor is high temperature requirement A (HtrA), which possesses chaperone and serine protease activity. In the host stomach, HtrA secreted from H. pylori (HpHtrA) disrupts intercellular adhesions by cleaving epithelial adhesion proteins including E-cadherin and desmoglein-2. This disruption causes intercellular junctions to open, allowing the bacterium to pass through the epithelial barrier, access the intercellular space, and colonize the gastric mucosa. HtrA proteases are well known for their structural complexity, reflected in their diverse oligomer forms and multi-tasking activities in both prokaryotes and eukaryotes. In this study, we determined crystal structures and solution conformations of HpHtrA monomer and trimer, which revealed large domain rearrangements between them. Notably, this is the first report of a monomeric structure in the HtrA family. We further found a pH-dependent dynamic trimer-to-monomer conversion and concurrent conformational changes that seem closely linked with a pH-sensing ability through the protonation of certain Asp residues. These results advance our understanding of the functional roles and the related mechanisms of this protease in bacterial infection, which may shed light on the development of HtrA-targeted therapies for H. pylori-associated diseases.

Reproductive outcomes after uterine septum resection in patients with recurrent miscarriage or infertility: a retrospective study in Chinese women.

OBJECTIVE: Septate uterus is the most common structural uterine anomaly, which is related to the adverse pregnancy outcomes in women of childbearing age. This article provides a retrospective review of hysteroscopic uterine septum resection performed in our hospital during recent years, focusing on the patients with recurrent miscarriage and primary infertility, and also to identify which patients are more likely to benefit from the surgery. METHODS: This is a single-center retrospective study. Cases of women who underwent hysteroscopic septum resection at West China Second Hospital of Sichuan University from January 2014 to December 2019, retrieved through the medical record system, were divided into three groups: Group A was the recurrent miscarriage group, Group B had a history of pregnancy with spontaneous abortion once at most, and Group C was the primary infertility group. Each patient was followed up by telephone about further pregnancy, miscarriage and live birth for at least 1 year. RESULTS: A total of 176 surgical patients were included in this study. Group A, B, and C include 42, 74, and 60 cases, respectively. The postoperative pregnancy rates of the three groups were 71.4, 82.4, and 75.0%; live births rates were 50.0, 74.3, and 71.7%; and spontaneous abortion rates were 21.4, 17.6, and 13.3%. 62 patients had a complete uterine septum and 114 had a partial uterine septum. For patients with complete septate uterus, the preoperative pregnancy rate was 54.84% and the pregnancy rate increased to 85.48% after surgery; and yet the preoperative and postoperative pregnancy rates in patients with partial septate uterus were close (from 71.9 to 72.8%). CONCLUSIONS: After uterine septum resection, the pregnancy rate and spontaneous abortion rate in RSA patients were not significantly different from the other two groups, but the live birth rate was still significantly lower. Patients with complete uterine septum may benefit more from surgery. The surgical indications should be carefully and strictly evaluated.

Effect of anterior capsule polishing on the visual quality after cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the effect of anterior capsule polishing on visual quality after phacoemulsification.METHODS: Prospective randomized control study. A total of 65 patients(73 eyes)with age-related cataract who underwent phacoemulsification combined with intraocular lens(IOL)implantation in the Emergency General Hospital between November 2021 and June 2022 were included. These patients were randomly assigned to two groups, with one group(anterior polishing group)underwent anterior and posterior capsule polishing(30 cases, 35 eyes), while the other(control group)receive routine posterior capsule polishing(35 cases, 38 eyes). Best corrected visual acuity was observed at 1wk, 1, 3 and 6mo after operation. Area of anterior capsule orifice was measured at 3 and 6mo after operation. Meanwhile, posterior capsular opacification(P score), IOL tilt and decentration were recorded by Pentacam Scheimpflug system. In addition, wavefront aberration, Strehl ratio(SR)of point spread function(PSF)and modulation transfer function(MTF)were evaluated by OPD-Scan Ⅲ.RESULTS: At 1wk, 1, 3 and 6mo after operation, best corrected visual acuity in anterior polishing group is significantly better than that of control group(P&#x003C;0.05). There were no significant differences in area of anterior capsule opening, P score, IOL decentration, SR of PSF and MTF between two groups at 3 and 6mo after operation(P&#x003E;0.05). At 3mo follow-up, no significant differences in IOL tilt and wavefront aberration were measured between two groups either(P&#x003E;0.05). However, IOL tilt [(1.65±0.60)° vs.(2.34±0.43)°, P&#x003C;0.001] and wavefront aberration(0.03±0.01μm vs. 0.06±0.03μm, P&#x003C;0.001)in anterior polishing group were significant lower compared to control group at 6mo after operation.CONCLUSION: 360° polishing of anterior and posterior capsule during phacoemulsification can improve best corrected visual quality, with reduced IOL tilt, lower wavefront aberration and better visual quality.

Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice / 中华内科杂志

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) μg/mg vs. (0.974±0.060) μg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) μg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.

Clinical characteristics, treatment and vaccination effect of SARS-CoV-2 Omicron variant infection in kidney transplant recipients abroad / 中华器官移植杂志

The Omicron variant of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious, but compared to early virus typing has milder symptoms and better prognosis.This article reviewed and analyzed the clinical characteristics, treatment, prognosis and vaccination effect of Omicron infection in Kidney transplant recipients (KTR) in recent years.The clinical manifestations of KTR infected with Omicron and the comparison with early variants, the clinical characteristics of KTR infected with Omicron compared with the general population, the treatment of KTR infected with Omicron after foreign countries, the effect of vaccination on KTR to prevent Omicron and the measures to increase the ted of vaccine, the summary of the prevention and treatment of KTR infected with Omicron abroad and the experience and the shortcomings of the current researches were analyzed and summarized.

Factors associated with acute rejection after pediatric kidney transplantation: a single-center cohort study / 中华器官移植杂志

Objective:To summarize the incidence of acute rejection (AR) after pediatric kidney transplantation (KT) at a single center and examine its impact on graft/patient survival and risk factors for AR.Methods:This is a retrospective cohort study including pediatric recipients who underwent kidney transplantation in past 8 years.After excluding recipients of graft thrombosis within a week post-transplant and lost to follow-ups, a total of 143 cases were ultimately recruited and assigned into two groups of AR (n=29) and non-AR (n=114).Basic profiles of both donors and recipients and graft/patient survival rate were compared between two groups.Relative risk factors for AR episodes were also examined by Logistic regression.Results:Renal grafts for 130/143 cases (90.9%) were harvested from deceased donors and 120(83.9%) cases from children.Twenty-seven transplants (18.9%) were performed in infants and young recipients aged < 3 years.During a median follow-up of 33 months, 34 AR episodes occurred in 29(20.3%) patients.Rate of re-transplantation (27.6% vs. 7.9%), pediatric donor (96.5% vs. 80.7%) and rabbit anti-human thymocyte globulin (rATG) induction (79.3% vs. 36%) were significantly higher in AR group than non-AR group ( P=0.007, P=0.046, P<0.001).Multivariate regression analysis indicated that basiliximab induction caused a significant reduction in the risk of AR incidence as compared with rATG induction (odds ratio 0.13, 95% confidence interval 0.04-0.43, P<0.001).The median time of AR incidence was 1.3 months post-transplantation and 23 episodes (67.6%) were confirmed by biopsy.After anti-rejection treatment, 52.9%(n=18) of the cases achieved a full recovery and 38.3% (n=13) had improved graft function.However, 3 cases (8.8%) developed irreversible graft failure.The 1/3-year graft survival rates were significantly lower in AR group than those in non-AR group (75.3% vs. 95.2%, 68.4% vs. 90.4%, P=0.01), and there was no significant difference in 1-and 3-year patient survival rates between two groups. Conclusions:The incidence of AR is relatively high in pediatric renal transplantation, which has an impact on graft survival.Basiliximab induction can effectively reduce the risk of AR.

Recent advances in preclinical research of renal xenotransplantation and selection of potential recipients in the future / 中华器官移植杂志

After continuous efforts from generations of transplant surgeons, kidney transplantation (KT) has become an optimal treatment for end-stage renal disease.However, an imbalance between supply and demand of organs has always restricted the development of KT.For this clinical dilemma, xenotransplantation is expected to become one practical alternative for alleviating organ shortage.This review summarized recent literature reports of kidney xenotransplantation and the latest cases of pig-to-human kidney and heart transplantations.Also clinical transformations and applications of kidney xenotransplantation were discussed.

Comparison of image quality based on deep-learning image reconstruction and iterative reconstruction algorithm for dual-energy CT: a phantom and animal-model study / 中华放射学杂志

Objective:To investigate the impact of the deep learning reconstruction algorithm TrueFidelity TM for Gemstone Spectral Imaging (TF-GSI) and the adaptive statistical iterative reconstruction algorithm (ASiR-V, hereinafter referred to as ASiR-V) based on phantom and animal models on the image quality of dual-energy CT images. Methods:GE Revolution Apex CT was used to scan the ACR 464 phantom and a mouse model of gastric cancer with lymph node metastasis ( n=16). TF-GSI and ASiR-V were separately used to reconstruct middle and high-grade images (TF-GSI-M, TF-GSI-H, ASiR-V-50%, and ASiR-V-100%) on the phantom and mouse based on virtual monoenergetic images at 70 keV. The task transfer function (TTF) of bone and acrylic, image noise power spectrum (NPS), and detectability index (d′) of the phantom images were evaluated. One-way ANOVA analysis was used to compare the image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for brain and liver on images of mice. The consistency of the two reconstruction-algorithm images (TF-GSI-H and ASiR-V100%) in the detection of small lesions by two radiologists (A and B) was evaluated using kappa test. Results:In terms of the phantom, the TF-GSI-H group had the best performance in TTF, NPS, and d′. Compared to ASiR-V-100%, the TTF50% of bone and acrylic in the TF-GSI-H group increased by 2.4% and 8.9%, respectively; the NPS peak decreased by 54.1%, compared to ASiR-V-100%; the d′ of bone and acrylic in the TF-GSI-H group relative to ASiR-V-100% increased by 52.7% and 59.5%, respectively. The TF-GSI group had reduced image noise compared to the ASiR-V group, and both SNR and CNR of the two tissues increased, but the differences between the groups were not statistically significant (all P>0.05). The two reconstruction-algorithm images showed good consistency in image evaluation by the two radiologists (A, Kappa=0.875, P<0.001; B, Kappa=0.625, P=0.012). In terms of the detection of micro-metastases in mice, the TF-GSI group outperformed the ASiR-V group (average accuracy: 83.5% vs 71.9%; average sensitivity: 77.8% vs 61.2%; average specificity: 85.7% vs 85.7%). Conclusion:Compared with iterative reconstruction algorithm, the DLIR algorithm showed improved spatial resolution, reduced image noise, and enabled detectability of micro-lesion for images from dual-energy CT.

Sustained high glucose intake accelerates type 1 diabetes in NOD mice.

Introduction: Epidemiological studies have suggested that dietary factors, especially high consumption of high glycaemic index carbohydrates and sugars, may trigger or exacerbate the progression of type 1 diabetes. We aimed to provide experimental evidence to confirm this relevance and to explore the underlying mechanisms. Methods: NOD mice were given sustained high-glucose drinking or glucose-free water and observed for the incidence of type 1 diabetes and islet inflammation. RNAseq was performed to detect the transcriptome changes of the NOD islet beta cell line NIT-1 after high glucose treatment, and mass spectrometry was performed to detect the proteome changes of NIT-1-cells-derived sEVs. Results: Sustained high glucose drinking significantly aggravates islet inflammation and accelerates the onset of type 1 diabetes in NOD mice. Mechanistically, high glucose treatment induces aberrant ER stress and up-regulates the expression of autoantigens in islet beta cell. Moreover, high glucose treatment alters the proteome of beta-cells-derived sEVs, and significantly enhances the ability of sEVs to promote DC maturation and stimulate immune inflammatory response. Discussion: This study provides evidence for negative effect of high glucose intake as a dietary factor on the pathogenesis of type 1 diabetes in genetically predisposed individuals. Therefore, avoiding high sugar intake may be an effective disease prevention strategy for children or adults susceptible to type 1 diabetes.