Objective To preliminarily investigate the safety and efficacy of donor pancreas needle biopsy in simultaneous pancreas-kidney transplantation. Methods Clinical data of 7 cases undergoing donor pancreas biopsy were collected retrospectively. All cases underwent donor pancreas biopsy before or during simultaneous pancreas-kidney transplantation. Frozen section or paraffin sectioning techniques were used for tissue preparation, and hematoxylin-eosin and Masson staining were performed to histologically evaluate the donor pancreas. The quality of donor pancreas was comprehensively assessed by combining histological findings with the donor's clinical data. Postoperative follow-up data of 5 simultaneous pancreas-kidney transplant recipients were collected to summarize the safety of donor pancreas biopsy and the prognosis of transplant recipients. Results The 7 pancreas donors were aged 28 to 62 years, with a body mass index ranging from 20.76 to 27.68 kg/m². Liver ultrasound indicated fatty liver in 3 cases, while pancreatic ultrasound did not reveal any significant abnormalities. Among them, biopsy was performed on 2 donors after completion of pancreatic procurement and processing, and the frozen section histology showed moderate acute pancreatitis changes (edema of acinar cells, necrosis and inflammatory cell infiltration). Combined with a serum amylase level elevated more than 3 times the upper limit of normal value, these two donor pancreases were finally discarded. The remaining 5 cases underwent biopsy immediately after pancreatic vascular anastomosis during simultaneous pancreas-kidney transplantation, and histological evaluation was performed on paraffin-embedded sections. No biopsy-related complications (such as bleeding, pancreatic fistula, etc.) occurred after transplantation. One recipient died of severe infection 2 months after transplantation, while the other 4 recipients were followed up for more than 5 years, with well-functioning transplant kidneys and pancreases. Conclusions Donor pancreas biopsy is relatively safe, and the risk of biopsy-related complications after transplantation is controllable. Comprehensive assessment of donor pancreas quality by combining histological evaluation with the donor's clinical indicators is conducive to improving the accuracy of donor pancreas selection and organ utilization.

The development of the rare disease discipline is a crucial pathway for enhancing the diagnosis and treatment of rare diseases, cultivating specialized professionals, and fostering technological innovation. Currently, China' rare disease discipline is accelerating its development driven by both policy and demand. However, it still faces multi-dimensional challenges, including an incomplete clinical management mechanism, a shortage of interdisciplinary talents, a weak scientific research system, and limited outreach capacity. To address these challenges, this paper proposes and constructs an integrated development system with clinical diagnosis and treatment as the foundation, talent cultivation as the engine, scientific research as the support, and disciplinary outreach capacity as the extension. Specific strategies include: enhancing clinical management through artificial intelligence-assisted diagnosis systems and multidisciplinary collaboration platforms; strengthening the talent pool through textbooks, curricula, and hierarchical training mechanisms; bolstering research collaboration and translational outcomes by leveraging international data-sharing platforms, national rare disease medical centers, the State Key Laboratory of Complex Severe and Rare Diseases, and the National Key Scientific Infrastructure for Translational Medicine; and expanding grassroots outreach and public awareness through the National Rare Disease Diagnosis and Treatment Collaboration Network, the National Rare Disease Quality Control Center, and integrated media communication channels. In the future, the rare disease discipline should further deepen the integration of medicine and engineering, expand international cooperation, focus on the translational closed loop, improve the regional collaboration network, so as to build a more resilient and dynamic disciplinary ecosystem, and ultimately achieve a comprehensive improvement in the diagnosis and treatment of rare diseases.

[摘 要] 目的：探究乌头酸酶2（ACO2）发生核转位的条件和作用机制并探讨ACO2核转位对肝癌细胞PLC/PRF/5增殖、迁移和侵袭的影响。方法：借助Human Protein Atlas（HPA）数据库分析ACO2在人肝癌组织中的表达与亚细胞定位；利用NLStradamus网站预测ACO2的潜在核定位信号（NLS），并通过基因截短技术构建NLS缺失的ACO2基因（ACO2 ∆NLS）；将野生型（ACO2WT）及突变型（ACO2ΔNLS）质粒转染至人肝癌PLC/PRF/5细胞，分别在常氧及低氧（1% O₂）条件下培养；采用免疫荧光染色技术，分析低氧条件影响ACO2入核的机制；通过EdU染色、划痕实验及Transwell实验评估PLC/PRF/5细胞的增殖、迁移与侵袭能力；借助WB检测胞核和胞质中ACO2的表达水平以及迁移、侵袭相关蛋白MMP2与MMP9表达水平的变化。结果：HPA数据库分析显示，ACO2在肝癌细胞的细胞核和细胞质中均呈高表达；免疫荧光染色和WB结果显示，低氧能够以NLS依赖的方式显著诱导ACO2发生核转位（均P < 0.01）；功能学实验显示，低氧诱导的ACO2核转位能进一步显著促进PLC/PRF/5细胞的增殖、迁移（均P < 0.05）和侵袭（均P < 0.05）能力。WB实验表明，ACO2核转位可上调迁移、侵袭相关蛋白MMP2与MMP9的表达水平（均P < 0.05）。结论：低氧能以NLS依赖的方式诱导ACO2发生核转位，从而增强PLC/PRF/5细胞的增殖、迁移和侵袭能力。

Objective:To explore the value of neutrophil extracellular traps (NETs) and interleukin (IL)-33 in the early diagnosis of contrast-induced acute kidney injury (CIAKI).Methods:It was a prospective cohort study. The clinical data of patients who underwent coronary angiography (CAG) in Sir Run Run Hospital, Nanjing Medical University from December 2022 to December 2023 were collected. The main indicators of NETs included myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone H3 (H3Cit) and antimicrobial peptide LL-37 amide (LL-37). Serum samples were collected before CAG, and 2 hours and 12 hours after CAG, and the levels of MPO, NE, H3Cit, LL-37, IL-33 and neutrophil gelatinase-associated lipocalin (NGAL) were detected. The differences of clinical data between CIAKI group and non-CIAKI group were compared. Multivariate logistic regression model was applied to analyze the risk factors of CIAKI. The receiver- operating characteristic curve was used to evaluate the predictive performance of biomarkers. Spearman correlation analysis was used to analyze the correlations among those biomarkers.Results:A total of 280 eligible patients with CAG were included in this study, with age of (65±13) years and 203 males (72.5%). The incidence rate of CIAKI was 11.8% (33/280). Compared with non-CIAKI group, the proportions of diabetes ( χ2=5.302, P=0.021), preoperative positive urine protein ( χ2=6.871, P=0.009), taking beta-blockers ( χ2=4.580, P=0.032), diuretics ( χ2=21.987, P<0.001) and calcium channel blocker ( χ2=10.424, P=0.001), preoperative blood glucose ( Z=2.807, P=0.005), preoperative blood urea nitrogen ( Z=2.504, P=0.012), neutrophil at 24 hours after CAG ( Z=2.173, P=0.030), serum creatinine at 24 hours after CAG ( Z=4.000, P<0.001), and blood urea nitrogen at 24 hours after CAG ( Z=4.459, P<0.001) were higher, while the preoperative hemoglobin ( Z=-2.380, P=0.017) and serum albumin ( Z=-2.556, P=0.011) were lower in CIAKI group. Multivariate logistic regression analysis showed that increasing neutrophil at 24 hours after CAG ( OR=1.180，95% CI 1.037-1.341), diuretics ( OR=5.615，95% CI 2.294-13.745) and calcium channel blockers ( OR=3.141，95% CI 1.374-7.182) were independent influencing factors of CIAKI. There were statistically significant differences in the levels of serum NE, MPO, H3Cit, LL-37, NGAL and IL-33 among before CAG, 2 hours after CAG and 12 hours after CAG in the overall population, CIAKI group and non-CIAKI group (all P<0.05). In addition, the changes of IL-33 before CAG and 12 hours after CAG was positively correlated with the changes of MPO, NE, H3Cit, LL-37, NGAL, serum creatinine and blood urea nitrogen before CAG and 12 hours after CAG (all P<0.05). The levels of NE ( Z=3.435, P=0.001; Z=6.164， P<0.001), MPO ( Z=3.627, P<0.001; Z=4.729, P<0.001), H3Cit ( Z=5.174, P<0.001; Z=6.241, P<0.001), LL-37 ( Z=4.986, P<0.001; Z=6.346, P<0.001), NGAL ( Z=2.956, P=0.003; Z=4.263, P<0.001) and IL-33 ( Z=5.056, P<0.001; Z=6.240, P<0.001) in CIAKI group at 2 h and 12 h after CAG were significantly higher than those in non-CIAKI group. The receiver-operating characteristic curve indicated that the combined AUC of neutrophil 24 hours after CAG, diuretics and calcium channel blockers in predicting CIAKI was 0.791. NE ( AUC=0.701), MPO ( AUC=0.712), H3Cit ( AUC=0.777), LL-37 ( AUC=0.767) and IL-33 ( AUC=0.795) at 2 hours after CAG predicted CIAKI relatively well. NE ( AUC=0.865), MPO ( AUC=0.758), H3Cit ( AUC=0.834), LL-37 ( AUC=0.840) and IL-33 ( AUC=0.867) at 12 hours after CAG had better prediction effect for CIAKI. The AUC of NETs combined with IL-33 in predicting CIAKI at 2 hours and 12 hours after CAG was 0.874 and 0.956, respectively. Conclusions:CIAKI patients exhibit elevated levels of NETs and IL-33. Serum MPO, NE, H3Cit, LL-37 and IL-33 at 12 hours after CAG can predict the occurrence of CIAKI. The combination of NETs and IL-33 is more effective in predicting CIAKI.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Objective:To analyze the efficacy of phantom-less quantitative computer tomography (PL-QCT) for the diagnosis of osteoporosis in patients with lumbar degenerative diseases.Methods:From October 2021 to October 2023, a total of 1 248 patients with lumbar degenerative disease who did not receive anti-osteoporosis treatment in the Department of Spine Surgery, Tianjin Hospital were retrospectively analyzed. There were 520 males and 728 females, aged 62.31±9.37 years (range, 40-87 years), height 1.66±0.08 m (range, 1.43-1.89 m), weight 69.04±8.27 kg (range, 49-93 kg). The mean body mass index was 26.11±3.67 kg/m 2 (range, 14.40-37.11 kg/m 2). Dual-energy X-ray absorptiometry (DXA) and PL-QCT were used to diagnose osteoporosis, and the detection rates of the two diagnostic methods were compared. The receiver operating characteristic (ROC) curve of PL-QCT for the diagnosis of osteoporosis was drawn, the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity were calculated. Results:Among 1 248 patients with lumbar degenerative diseases, 626 (50.2%) were diagnosed as osteoporosis by PL-QCT, 423(33.9%) were diagnosed by spine DXA, 488(39.1%) were diagnosed by hip DXA and 539 patients(43.2%) were diagnosed by dual-site DXA. The detection rate of osteoporosis of PL-QCT was higher than that of spine DXA (χ 2=193.557, P<0.001), hip DXA (χ 2=322.201, P<0.001) and dual-site DXA (χ 2=94.683, P<0.001), and the difference was statistically significant. Taking the diagnostic results of spinal DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 79%, a specificity of 81%, and an AUC and 95% CI of 0.82(0.79, 0.85). Taking the diagnostic results of hip DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 85%, a specificity of 55%, and an AUC and 95% CI of 0.75(0.71, 0.78). Taking the diagnostic results of two-site DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 72%, a specificity of 75%, and an AUC and 95% CI of 0.81(0.78, 0.83). Conclusion:Compared with DXA, PL-QCT has a higher detection rate of osteoporosis in patients with degenerative lumbar spine disease and good diagnostic efficacy.

Objective:To investigate the clinical efficacy of lumbar lateral interbody fusion (LLIF) versus posterior lumbar interbody fusion (PLIF) in the treatment of severe lumbar spinal stenosis.Methods:The data of patients with severe lumbar spinal stenosis who underwent LLIF or PLIF from February 2019 to December 2023 were retrospectively analyzed. There were 30 patients in the LLIF group, 10 males and 20 females, aged 62.7±5.6 years (range, 53-74 years), including 21 cases of single segment and 9 cases of double segment. There were 46 patients in the PLIF group, including 20 males and 26 females, aged 63.2±8.4 years (range, 43-75 years), 40 cases of single segment and 6 cases of double segment. The visual analogue scale (VAS), Oswestry disability index (ODI), intervertebral space height, intervertebral foramen height and postoperative complications were compared between the two groups.Results:All patients were followed up for an average of 21.3±6.4 months (range, 12-32 months). The intraoperative blood loss in the LLIF group was 112.2±76.9 ml, which was significantly lower than 193.9±88.2 ml in the PLIF group ( P<0.05). The VAS scores of back pain and leg pain after operation were significantly lower than those before operation in the two groups ( P<0.05). There was no statistically significant difference between groups in back pain VAS scores at preoperative, 6 months postoperative, and final follow-up ( P>0.05); the back pain VAS score at 1 month postoperatively in the LLIF group was 1.6±1.2, which was less than 2.8±0.7 in the PLIF group ( P<0.05). There was no statistically significant difference between groups in leg pain VAS scores at preoperative, 1 month postoperative, and 6 months postoperative ( P>0.05); the leg pain VAS score at the final follow-up in the LLIF group was 1.2±1.5, which was smaller than 1.8±1.0 in the PLIF group ( P<0.05). The postoperative ODI was smaller than the preoperative one in both groups, and the difference was statistically significant ( P<0.05); the preoperative, 1-month postoperative, 6-month postoperative, and final follow-up ODIs in the LLIF group were 45.7%±16.0%, 17.9%±12.0%, 16.2%±11.6%, and 15.7%±11.7%, and those in the PLIF group were 47.9%±15.4%, 20.1%±9.3%, 16.9%±10.6%, and 14.6%±11.0% in the PLIF group, and the difference between the groups was not statistically significant ( P>0.05). The preoperative intervertebral space height in the LLIF group was 10.6±2.0 mm, which was smaller than that in the PLIF group 11.8±2.2 mm ( P<0.05). The intervertebral space heights in the immediate postoperative period and at the final follow-up were 13.3±2.3 mm and 12.3±2.2 mm in the LLIF group and 13.7±1.7 mm and 13.0±1.9 mm in the PLIF group ( P>0.05). The preoperative intervertebral foraminal height in the LLIF group was 18.0±3.2 mm, which was smaller than that of 19.7±2.4 mm in the PLIF group ( P<0.05); the intervertebral foraminal heights in the immediate postoperative period and at the final follow-up were 21.4±2.5 mm and 20.2±2.4 mm in the LLIF group, and in the PLIF group were 20.7±2.4 mm and 19.7±2.6 mm in the PLIF group ( P>0.05). In the LLIF group, 2 cases had femoral nerve injury and 2 cases had transient back pain after operation. There were 2 cases of cerebrospinal fluid leakage, 1 case of screw loosening, and 2 cases of deep vein thrombosis in the PLIF group. In the PLIF group, 2 patients underwent revision, including 1 case due to cage displacement and 1 case due to screw malposition. The fusion settling rate was 21% (8/39) in the LLIF group and 12% (6/52) in the PLIF group ( P>0.05). Conclusion:Both LLIF and PLIF can effectively restore the intervertebral height, improve the lumbar function and the symptoms of back and leg pain in the treatment of severe lumbar spinal stenosis.

Objective:To investigate the risk factors for complications following lateral lumbar interbody fusion (LLIF) surgery.Methods:A retrospective analysis was conducted on 196 patients who underwent LLIF surgery via the psoas major muscle approach in the Department of Spinal Surgery, Tianjin Hospital, Tianjin University, from October 2018 to July 2024. The age, gender, body mass index (BMI), presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, operative time, surgical segments (whether the surgery was single-segment or multi-segments), and use of internal fixation or not were compared between patients with and without postoperative complications, the indicators with P<0.10 were included in the binary variable logistic regression analysis, and determine the independent risk factors for complications after LLIF surgery. Complications included anterior thigh symptoms (pain, numbness, weakness), cage subsidence, surgery-related complications (nerve injury, surgical site infection, postoperative buttock pain, urinary and fecal incontinence, etc.), and medical complications (cerebrovascular accident, deep vein thrombosis, urinary tract infection, etc.). Results:All 196 patients were followed up for 27.02 (12.6, 40.69) months. Postoperative complications occurred in 71 cases (96 times), and no complications occurred in 125 cases. In the complication group, there were 15 males and 56 females with a mean age of 61.82±7.57 years; in the non-complication group, there were 43 males and 82 females with a mean age of 62.00± 8.39 years. In the complication group, there were 43 cases of anterior thigh symptoms, 38 cases of cage subsidence, 11 cases of surgical operation-related complications, and 4 cases of medical complications. There were statistically significant differences in gender (χ 2=3.829, P=0.051), operation time ( t=2.391, P=0.018), and surgical segment (χ 2=4.245, P=0.039) between the complication group and the non-complication group. No statistically significant differences were found in age, gender, BMI, presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, or use of internal fixation ( P>0.10). Binary variable logistic regression analysis indicated that prolonged operative time [ OR=1.007, 95% CI(1.001, 1.013), P=0.019] and multilevel surgery [ OR=2.099, 95% CI(1.095, 4.025), P=0.026] were independent risk factors for complications following LLIF. Conclusion:Prolonged operative time and multi-segments surgery are independent risk factors for complications following LLIF.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.