Validity of the modified versions of SARC-F+EBM for sarcopenia screening and diagnosis in China: the PPLSS study.

BACKGROUND AND OBJECTIVES: It is recommended by Asian Working Group for Sarcopenia to early identify people at risk for sarcopenia using simple screening tools like SARC-F. The modified version SARC-F+EBM showed higher diagnostic performance. However, this cut-off value of body mass index (BMI) remained uncertain to be used in Chinese population. In this study, we used appropriate BMI recommended for Chinese older population and further modified SARC-F+EBM by combining calf circumference. METHODS AND STUDY DESIGN: Diagnostic tests were performed and the receiver operating characteristics analyses were conducted between the SARC-F, SARC-F+EBM (cut-off of BMI: ≤ 21 kg/m2), SARC-F+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2), SARC-CalF and SARC-CalF+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2) in 1660 community-dwelling participants aged ≥ 65 years from China. RESULTS: The participants had an average age of 71.7±5.1 years, of which 56.8% were women. All the modified models could enhance the areas under the receiver operating characteristic curve (AUC) of original SARC-F (all p<0.001). The SARC-F+EBM (CN) also showed a significantly higher sensitivity of 47.4% (p<0.001) and an AUC of 0.809 (p=0.005) than SARC-F+EBM. SARC-CalF+EBM (CN) was validated to be of great diagnostic value of the highest AUC of 0.88 among these sarcopenia screening tools, including SARC-F, SARC-CalF and SARC-F+EBM (CN) (all p<0.001). Using this study population as a reference, the optimal cut-off value of SARC-CalF+EBM (CN) is ≥12 points, with a sensitivity of 79.3% and a specificity of 80.7%. CONCLUSIONS: The SARC-F+EBM (CN) and SARC-CalF+EBM (CN) could enhance the diagnostic performance of SARC-F and SARC-F+EBM and are suitable sarcopenia screening tools for Chinese population.

Tetrasulfide bond boosts the anti-tumor efficacy of dimeric prodrug nanoassemblies.

Dimeric prodrug nanoassemblies (DPNAs) stand out as promising strategies for improving the efficiency and safety of chemotherapeutic drugs. The success of trisulfide bonds (-SSS-) in DPNAs makes polysulfide bonds a worthwhile focus. Here, we explore the comprehensive role of tetrasulfide bonds (-SSSS-) in constructing superior DPNAs. Compared to trisulfide and disulfide bonds, tetrasulfide bonds endow DPNAs with superlative self-assembly stability, prolonged blood circulation, and high tumor accumulation. Notably, the ultra-high reduction responsivity of tetrasulfide bonds make DPNAs a highly selective "tumor bomb" that can be ignited by endogenous reducing agents in tumor cells. Furthermore, we present an "add fuel to the flames" strategy to intensify the reductive stress at tumor sites by replenishing exogenous reducing agents, making considerable progress in selective tumor inhibition. This work elucidates the crucial role of tetrasulfide bonds in establishing intelligent DPNAs, alongside the combination methodology, propelling DPNAs to new heights in potent cancer therapy.

Phytochemicals, antioxidant capacities and volatile compounds changes in fermented spicy Chinese cabbage sauces treated by thermal and non-thermal technologies.

To extend shelf life of fermented spicy Chinese cabbage sauce at room temperature, the effects of electron beam irradiation (EBI), high pressure processing (HPP), pasteurization (PT) and autoclave sterilization (AS) treatments on the colony counts of Lactobacillus plantarum, phytochemicals, antioxidant activities and volatile compounds were investigated. Results showed that thermal and non-thermal treatments could significantly decrease the colony counts of Lactobacillus plantarum, in which EBI and AS treatments inactivated Lactobacillus plantarum thoroughly. EBI and HPP treatments were superior to PT and AS treatments in terms of volatile compounds, bioactive compounds and antioxidant activities. The total contents of volatile compounds in sauces treated by EBI and HPP were significantly increased by 43.92%-61.87% and 71.53%-84.46%, respectively, and the new formed substance 2,3-butanedione endowed sauces with sweet and creamy aroma. In addition, HPP treatment improved the extractable contents of total phenolics and carotenoids, retained capsicum red pigment content, and significantly enhanced antioxidant capacities of sauces. Sauce treated by HPP at 200 MPa exhibited the highest total carotenoid content, DPPH radical scavenging activity and FRAP, increasing by 9.27%, 2.24% and 16.13%, respectively, compared with CK. EBI treatment exhibited higher total phenolic content and FRAP, which positively depended on the dose. Therefore, HPP and EBI treatments were suggested as potential technologies to improve shelf-life stability and volatile compounds of fermented spicy Chinese cabbage sauce.

Sentrin-specific protease 1 maintains mitochondrial homeostasis through targeting the deSUMOylation of sirtuin-3 to alleviate oxidative damage induced by hepatic ischemia/reperfusion.

Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes a substantial economic burden in clinical practice, especially in liver surgery. Sentrin-specific protease 1 (SENP1) is a crucial enzyme involved in the regulation of SUMOylation, and is related to various diseases. However, the role of SENP1 in HIRI remains unexplored. Here, we confirmed that SENP1 actively participated in modulating the oxidative damage induced by HIRI. Notably, SENP1 functioned by maintaining mitochondrial homeostasis. Further mechanistic exploration indicated that the protective mitochondrial protein sirtuin-3 (Sirt3) was inactivated by SUMOylation during HIRI, which was reversed by SENP1. Overexpression of SENP1 could restore mitochondrial function, mitigate oxidative stress and attenuated apoptosis through recovering the expression of Sirt3 during HIRI. Nevertheless, 3-TYP, an inhibitor of Sirt3, could eliminate the therapeutic effects brought by overexpression of SENP1. In conclusion, our findings demonstrated that SENP1 mediated the deSUMOylation of Sirt3 and maintained mitochondrial homeostasis, thus alleviating HIRI induced oxidative damage. SENP1 might be a promising therapeutic target for HIRI.

A prediction model for high ovarian response in the GnRH antagonist protocol.

Backgrounds: The present study was designed to establish and validate a prediction model for high ovarian response (HOR) in the GnRH antagonist protocol. Methods: In this retrospective study, the data of 4160 cycles were analyzed following the in vitro fertilization (IVF) at our reproductive medical center from June 2018 to May 2022. The cycles were divided into a training cohort (n=3121) and a validation cohort (n=1039) using a random sampling method. Univariate and multivariate logistic regression analyses were used to screen out the risk factors for HOR, and the nomogram was established based on the regression coefficient of the relevant variables. The area under the receiver operating characteristic curve (AUC), the calibration curve, and the decision curve analysis were used to evaluate the performance of the prediction model. Results: Multivariate logistic regression analysis revealed that age, body mass index (BMI), follicle-stimulating hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH) were independent risk factors for HOR (all P< 0.05). The prediction model for HOR was constructed based on these factors. The AUC of the training cohort was 0.884 (95% CI: 0.869-0.899), and the AUC of the validation cohort was 0.884 (95% CI:0.863-0.905). Conclusion: The prediction model can predict the probability of high ovarian response prior to IVF treatment, enabling clinicians to better predict the risk of HOR and guide treatment strategies.

Up-regulated SPP1 increases the risk from IPF to lung cancer via activating the pro-tumor macrophages.

The incidence of lung cancer (LC) in Idiopathic Pulmonary Fibrosis (IPF) patients is more than twice that in non-IPF. This study aims to investigate IPF-to-LC pathogenesis and to develop a predictor for detecting IPF predisposing patients to LC. We conducted unsupervised clustering to detect high-risk subtypes from IPF to LC. Subsequently, we performed single-cell RNA-seq analysis to characterize high-risk IPF by examining the immune microenvironment. We identified 42 common immune function-related pathogenic genes between IPF and LC. We developed an LC risk classifier for IPF patients, comprising five genes: SPP1, MMP9, MMP12, FABP4, and IL1B. The five-gene classifier can successfully distinguish the high-risk population from IPF patients. High-risk IPF patients exhibited an immunosuppressive microenvironment with higher oncogene expression than low-risk patients. Single-cell analysis revealed that SPP1+ macrophages at the terminal of macrophages' developmental trajectory may promote the progression from IPF to LC. The strong crosstalk between SPP1+ macrophages and inflammation-related cancer-associated fibroblasts promoted the tumorigenic process in IPF. In vitro, assays showed that co-culturing macrophages overexpressing SPP1 with MRC-5 cells induced the transition of fibroblasts into cancer-associated fibroblasts. SPP1 produced by macrophages promoted epithelial-mesenchymal transition in alveolar epithelial cells via stimulating the upregulation of N-cadherin and Vimentin in MLE-12 cells. This study provided a novel method to identify the LC risk population from IPF, revealing the cellular interactions involved in the transition from IPF to LC. Our findings highlighted SPP1 as a critical driver in IPF progression, offering a potential target for therapy in fibrosis.

Multi-omics integration analysis unveils heterogeneity in breast cancer at the individual level.

Identifying robust breast cancer subtypes will help to reveal the cancer heterogeneity. However, previous breast cancer subtypes were based on population-level quantitative gene expression, which is affected by batch effects and cannot be applied to individuals. We detected differential gene expression, genomic, and epigenomic alterations to identify driver differential expression at the individual level. The individual driver differential expression reflected the breast cancer patients' heterogeneity and revealed four subtypes. Mesenchymal subtype as the most aggressive subtype harbored deletion and downregulated expression of genes in chromosome 11q23 region. Specifically, silencing of the SDHD gene in 11q23 promoted the invasion and migration of breast cancer cells in vitro by the epithelial-mesenchymal transition. The immunologically hot subtype displayed an immune-hot microenvironment, including high T-cell infiltration and upregulated PD-1 and CTLA4. Luminal and genomic-unstable subtypes showed opposite macrophage polarization, which may be regulated by the ligand-receptor pairs of CD99. The integration of multi-omics data at the individual level provides a powerful framework for elucidating the heterogeneity of breast cancer.

Autoimmune receptor encephalitis in ApoE­/­ mice induced by active immunization with NMDA1.

Subacute progressive neuropsychiatric symptoms with cognitive and motor impairment and autoimmune seizures are some of the typical symptoms of anti­N­methyl­D­aspartate receptor (anti­NMDAR) encephalitis. The mechanisms underlying this disease are yet to be elucidated, which could be partly attributed to the lack of appropriate animal models. The present study aimed to establish an active immune mouse model of anti­NMDAR encephalitis. Mice were immunized with the extracellular segment of the NMDA1 protein, then subjected to open­field and novel object recognition experiments. Plasma was collected after euthanasia on day 30 after immunization and anti­NMDA1 antibodies were detected using ELISA. Furthermore, brain slices were analyzed to measure postsynaptic density protein 95 (PSD­95) and NMDA1 expression. Western blot analysis of NMDA1 and PSD­95 protein expression levels in the hippocampus was also performed. In addition, protein expression levels of PSD­95 and NMDA1 in mouse neuronal HT­22 cells were evaluated. Compared with controls, mice immunized with NMDA1 exhibited anxiety, depression and memory impairment. Moreover, high anti­NMDA1 antibody titers were detected with ELISA and the levels of anti­NMDA1 antibody reduced postsynaptic NMDA1 protein density in the mouse hippocampus. These findings demonstrated the successful construction of a novel mouse model of anti­NMDAR encephalitis by actively immunizing the mice with the extracellular segment of the NMDA1 protein. This model may be useful for studying the pathogenesis and drug treatment of anti­NMDAR encephalitis in the future.

Hepatocellular SETDB1 Regulates Hepatic Ischemia-Reperfusion Injury through Targeting Lysine Methylation of ASK1 Signal.

Background: Hepatic ischemia-reperfusion injury (HIRI) stands as an unavoidable complication arising from liver surgery, profoundly intertwined with its prognosis. The role of lysine methyltransferase SET domain bifurcated 1 (SETDB1) in HIRI remains elusive, despite its confirmation as a potential therapeutic target for diverse diseases. Here, we investigated the mechanism by which SETDB1 regulated HIRI. Methods: RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis. To elucidate the impact of SETDB1 on HIRI, both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established. Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI. Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI. Results: We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis. Moreover, inhibition of SETDB1 could mitigate HIRI-induced liver damage, inflammation, and apoptosis. Through our comprehensive mechanistic investigation, we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1 (ASK1) and facilitates the methylation of its lysine residues. Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1, leading to a marked suppression of downstream c-Jun N-terminal kinase (JNK)/p38 signaling pathway activation. The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression. Conclusions: The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1-JNK/p38 pathway, thus involved in HIRI-induced inflammation and apoptosis. These results suggest that SETDB1 holds promise as a potential therapeutic target for mitigating HIRI.

A comprehensive survival and prognosis analysis of GPR55 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common subtype, accounting for about 90% of all primary liver cancers. The liver is rich in a large number of immune cells, thus forming a special immune microenvironment, which plays a key role in the occurrence and development of hepatocellular carcinoma. Nowadays, tumor immunotherapy has become one of the most promising cancer treatment methods. Immune checkpoint inhibitors (ICIs) combined with VEGF inhibitors are listed as first-line treatment options for advanced HCC. Therefore, the search for a potential biomarker to predict the response to immunotherapy in HCC patients is urgently needed. The G protein-coupled receptor 55 (GPR55), a lysophosphatidylinositol (LPI) receptor, has recently emerged as a potential new target for anti-tumor therapy. Previous studies have found that GPR55 is highly expressed in breast cancer, pancreatic cancer, skin cancer and cholangiocarcinoma, and is involved in tumor proliferation and migration. However, the role and mechanism of GPR55 in HCC has not been elucidated. Therefore, this article discusses the clinical significance of GPR55 in HCC and its correlation with the immune response of HCC patients, so as to provide theoretical basis for improving the prognosis of HCC.

Effects of body mass index and insulin resistance on first-time assisted conception and perinatal outcomes in young polycystic ovary syndrome patients.

Objective: The objective of the study was to explore the effect of body mass index (BMI) and insulin resistance (IR) levels on first-time assisted conception results and perinatal outcomes in young polycystic ovary syndrome (PCOS) patients. Design: This was a single-center, retrospective, observational cohort study. Patients: Young women with PCOS undergoing their first embryo transfer were included in the study. Main outcome measure: Early pregnancy loss rate was the main outcome measure. Results: The early pregnancy loss rate in the overweight + insulin resistance group (OW+IR group) was significantly higher than that in the non-overweight + non-insulin resistance group (NOW+NIR group) (18.16% vs. 9.02%, Bonferroni correction, P = 0.012). The early pregnancy loss rate in the non-overweight + insulin resistance group (NOW+IR group) and overweight + non-insulin resistance group (OW+NIR group) (18.18% and 17.14%, respectively) were also higher than that in the NOW+NIR group (6.07%), but the difference was not statistically significant (Bonferroni correction, all P > 0.05). No significant difference was found in clinical pregnancy rate, live birth rate, and macrosomia rate (all P > 0.05). After adjusting for confounding factors, BMI and IR levels were identified as independent risk factors for early pregnancy loss rate. Conclusion: BMI and IR levels are independent risk factors for early pregnancy loss in young PCOS patients during the first embryo transfer cycle. Multiple indicators should be considered when assessing pregnancy outcomes, which will promote individualized pregnancy guidance and treatment procedures for PCOS patients.

NCOA7 Regulates Growth and Metastasis of Clear Cell Renal Cell Carcinoma via MAPK/ERK Signaling Pathway.

NCOA7 is a nuclear receptor coactivator that is downregulated in a variety of cancers. However, the expression and prognostic significance of NCOA7 in clear cell renal cell carcinoma (ccRCC) remain unknown. The expression of NCOA7 in ccRCC tissues was analyzed using bioinformatics analysis, Western blotting, and immunohistochemistry. Kaplan-Meier analysis, the receiver operating characteristic (ROC) curve, and clinicopathological correlation analysis were used to assess the predictive power of NCOA7. Overexpression function tests were conducted in cells and mouse models to clarify the function and mechanism of NCOA7 in inhibiting the progression of ccRCC. NCOA7 expression was downregulated in all three subtypes of renal cell carcinoma, and only had significant prognostic value for patients with ccRCC. NCOA7 overexpression inhibited the proliferation, invasion, and metastasis of ccRCC cells in vivo and in vitro. Mechanistically, NCOA7 inhibited the MAPK/ERK pathway to regulate epithelial-mesenchymal transformation (EMT) and apoptosis, thereby inhibiting the progression of ccRCC. NCOA7 inhibits tumor growth and metastasis of ccRCC through the MAPK/ERK pathway, thus indicating its potential as a prognostic marker and therapeutic target for ccRCC.

Netrin Family Genes as Prognostic Markers and Therapeutic Targets for Clear Cell Renal Cell Carcinoma: Netrin-4 Acts through the Wnt/ß-Catenin Signaling Pathway.

Clear cell renal cell carcinoma (ccRCC, or KIRC) is the most common type of kidney cancer, originating within the renal cortex. The current outcomes for early diagnosis and late treatment of ccRCC are unsatisfactory. Therefore, it is important to explore tumor biomarkers and therapeutic opportunities for ccRCC. In this study, we used bioinformatics methods to systematically evaluate the expression and prognostic value of Netrin family genes in ccRCC. Through our analysis, three potential biomarkers for ccRCC were identified, namely NTNG1, NTNG2, and NTN4. Moreover, we performed in vitro and in vivo experiments to explore the possible biological roles of NTN4 and found that NTN4 could regulate ccRCC development through Wnt/ß-catenin signaling. We elucidate the molecular mechanism by which NTN4 modulates ß-catenin expression and nuclear translocation to inhibit ccRCC progression, providing a new theoretical basis for developing therapeutic targets for ccRCC. Thus, we suggest that Netrin-related studies may offer new directions for the diagnosis, treatment, and prognosis of ccRCC patients.

Influence of SPIO labelling on the function of BMSCs in chemokine receptors expression and chemotaxis.

Bone marrow-derived mesenchymal stem cells (BMSCs) are increasingly being used in bone marrow transplantation (BMT) to enable homing of the allogeneic hematopoietic stem cells and suppress acute graft versus host disease (aGVHD). The aim of this study was to optimize the labelling of BMSCs with superparamagnetic iron oxide particles (SPIOs), and evaluate the impact of the SPIOs on the biological characteristics, gene expression profile and chemotaxis function of the BMSCs. The viability and proliferation rates of the SPIO-labeled BMSCs were analyzed by trypan blue staining and CCK-8 assay respectively, and the chemotaxis function was evaluated by the transwell assay. The expression levels of chemokine receptors were measured by RT-PCR and flow cytometry. The SPIOs had no effect on the viability of the BMSCs regardless of the labelling concentration and culture duration. The labelling rate of the cells was higher when cultured for 48 h with the SPIOs. Furthermore, cells labeled with 25 µg/ml SPIOs for 48 h had the highest proliferation rates, along with increased expression of chemokine receptor genes and proteins. However, there was no significant difference between the chemotaxis function of the labeled and unlabeled BMSCs. To summarize, labelling BMSCs with 25 µg/ml SPIOs for 48h did not affect their biological characteristics and chemotaxis function, which can be of significance for in vivo applications.

Ubiquitin-specific protease 29 attenuates hepatic ischemia-reperfusion injury by mediating TGF-ß-activated kinase 1 deubiquitination.

Background and aims: In the course of clinical practice, hepatic ischemia/reperfusion (I/R) injury is a prevalent pathophysiological event and is caused by a combination of complex factors that involve multiple signaling pathways such as MAPK and NF-κB. USP29 is a deubiquitinating enzyme important during the development of tumors, neurological diseases, and viral immunity. However, it is unknown how USP29 contributes to hepatic I/R injury. Methods and results: We systematically investigated the role of the USP29/TAK1-JNK/p38 signaling pathway in hepatic I/R injury. We first found reduced USP29 expression in both mouse hepatic I/R injury and the primary hepatocyte hypoxia-reoxygenation (H/R) models. We established USP29 full knockout mice (USP29-KO) and hepatocyte-specific USP29 transgenic mice (USP29-HTG), and we found that USP29 knockout significantly exacerbates the inflammatory infiltration and injury processes during hepatic I/R injury, whereas USP29 overexpression alleviates liver injury by decreasing the inflammatory response and inhibiting apoptosis. Mechanistically, RNA sequencing results showed the effects of USP29 on the MAPK pathway, and further studies revealed that USP29 interacts with TAK1 and inhibits its k63-linked polyubiquitination, thereby preventing the activation of TAK1 and its downstream signaling pathways. Consistently, 5z-7-Oxozeaneol, an inhibitor of TAK1, blocked the detrimental effects of USP29 knockout on H/R-induced hepatocyte injury, further confirming that USP29 plays a regulatory role in hepatic I/R injury by targeting TAK1. Conclusion: Our findings imply that USP29 is a therapeutic target with promise for the management of hepatic I/R injury via TAK1-JNK/p38 pathway-dependent processes.

Global Transcriptomic Analyses Provide New Insight into the Molecular Mechanisms of Endocarp Formation and Development in Iron Walnut (Juglans sigillata Dode).

Iron walnut (Juglans sigillata Dode) is a native species in southwestern China that exhibits variation in both fruit morphology and shell thickness. However, the underlying molecular processes controlling hardened endocarp development in walnut has not yet been reported. Here, we generated transcriptional profiles of iron walnut endocarp at three developmental stages using "Dapao", the most common commercial variety. Using pairwise comparisons between these three stages, a total of 8555 non-redundant differentially expressed genes (DEGs) were identified, and more than one-half of the total DEGs exhibited significant differential expression in stage I as compared with stage II or stage III, suggesting that the first stage may ultimately determine the final characteristics of the mature walnut shell. Furthermore, in the clustering analysis of the above DEGs, 3682, 2349, and 2388 genes exhibited the highest expression in stages I, II, and III, respectively. GO enrichment analysis demonstrated that the major transcriptional variation among the three developmental stages was caused by differences in cell growth, plant hormones, metabolic process, and phenylpropanoid metabolism. Namely, using the tissue-specific expression analysis and a gene co-expression network, we identified MADS-box transcription factor JsiFBP2 and bHLH transcription factor JsibHLH94 as candidate regulators of endocarp formation in the early stage, and JsiNAC56 and JsiMYB78 might play key roles in regulating the lignification process of endocarp in the late stage. This study provides useful information for further research to dissect the molecular mechanisms governing the shell formation and development of iron walnut.

MAPK Signaling Pathways in Hepatic Ischemia/Reperfusion Injury.

The mitogen-activated protein kinase signaling pathway can be activated by a variety of growth factors, cytokines, and hormones, and mediates numerous intracellular signals related to cellular activities, including cell proliferation, motility, and differentiation. It has been widely studied in the occurrence and development of inflammation and tumor. Hepatic ischemia-reperfusion injury (HIRI) is a common pathophysiological phenomenon that occurs in surgical procedures such as lobectomy and liver transplantation, which is characterized by severe inflammatory reaction after ischemia and reperfusion. In this review, we mainly discuss the role of p38, ERK1/2, JNK in MAPK family and TAK1 and ASK1 in MAPKKK family in HIRI, and try to find an effective treatment for HIRI.

A case report of two Chinese monozygotic twins with NPHP1 gene-associated nephronophthisis undergoing kidney transplantation from a related living-donor.

BACKGROUND: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and the most common hereditary disease leading to end-stage renal disease in children and adolescents. The NPHP1 gene was the first NPHP gene to be discovered. Pathogenic variation of the NPHP1 gene can cause juvenile renal wasting disease type 1. CASE PRESENTATION: Here, we report the first case of living related kidney transplantation of monozygotic twins with NPHP1 nephronophthisis in China; one of these cases involved cross-blood type kidney transplantation. Our experience shows that patients with NPHP1 nephronophthisis have almost no risk recurrent kidney disease following living related kidney transplantation and genetic testing. The two twins recovered well without any complications. CONCLUSIONS: This is the first report of living related kidney transplantation of monozygotic twins with heterozygous deletion of the NPHP1 gene in a Chinese family with NPHP. In addition, genetic testing provides an efficient means of evaluating the safety of living related kidney transplantation in patients with NPHP1 nephronophthisis.

Delayed closure of the anterior fontanelle in Iron Age children from Zaghunluq, northwestern China.

Delayed closure of the anterior fontanelle is often associated with various disorders. However, the phenomenon might be a normal variation. In this study, the anterior fontanelle was investigated in children from the Iron Age Zaghunluq cemetery in Xinjiang, northwestern China. Age at death was estimated by tooth development/eruption in the children. The anterior fontanelle was visually assessed for delayed fusion. Three out of nine children aged between 3-6 years old from the cemetery had signs of open anterior fontanelle. However, there were no signs of craniofacial pathology or developmental disruption. Delayed closure of the anterior fontanelle might have been a norm in the Iron Age Zaghunluq population. However, it is impossible to determine the reasons behind the high prevalence of delayed AF closure at Zaghunluq. Additional studies are warranted to determine whether this phenomenon is population specific, or diet specific, or just an individual variation.

Recent estimates and predictions of 5-year survival rate in patients with pancreatic cancer: A model-based period analysis.

Background: The 5-year survival rate for pancreatic cancer (PC) is incredibly low, resulting in this often being a fatal disease. Timely and accurate assessment of the survival rate and prognosis of patients with PC is of great significance for the development of new programs for prevention, monitoring, and treatment. Methods: Period analysis and further stratified analysis were used to determine the 5-year relative survival rate (RSR) of patients with PC from 2002 to 2016 using the Surveillance, Epidemiology, and End Results (SEER) project database of the National Cancer Institute. Based on this, a generalized linear model was created to predict the survival rate of patients from 2017 to 2021. Result: During 2002-2016, the 5-year RSR of patients with PC increased from 7.9 to 23.7%. The generalized linear model predicted that the survival rate had increased to 33.9% during 2017-2021, and hence, it was still unacceptably low. The survival rate of patients aged ≥75 years at diagnosis was the lowest among all age groups and was predicted to be only 21.4% during 2017-2021. Notably, the survival rate of patients with differentiation grade III at diagnosis remains particularly low at 7.6%. Conclusion: The survival rates of patients with PC, although slightly improved, remain extremely low. Timely assessment of the trend of survival rate changes in patients with PC further improves the prognosis of tumor patients and provides data support for relevant medical works to formulate effective tumor prevention and control policies.