ObjectiveTo systematically analyze the epidemiological characteristics and cause-of-death distribution among death cases with hepatitis C in Hongkou District of Shanghai, and to provide a scientific basis for optimizing healthcare resources allocation and targeted hepatitis C prevention and control measures. MethodsA retrospective cross-sectional study was conducted by integrating historical surveillance data from China Information System of Disease Prevention and Control and Shanghai Hongkou District Death Medical Registration System. Data on demographic characteristics, hepatitis C-related clinical and management records, and underlying causes of death for cases with hepatitis C between 2012 and 2024 in Hongkou District of Shanghai, were collected. Descriptive analyses were performed to analyze the epidemiological characteristics and cause-of-death distribution of death cases, and comparative analyses were conducted across different subgroups. ResultsA total of 204 hepatitis C-related deaths were identified in Hongkou District, Shanghai, from 2012 to 2024. The average age at death was (69.49±12.75) years The majority decedents were males (71.57%) and retired (73.53%). The top three underlying causes of death were malignant tumors (45.10%), cerebrovascular diseases (15.20%) and cardiovascular diseases (12.25%), collectively accounting for 72.55% of all deaths. Deaths attributed to hepatitis C accounted for 9.80% (20/204), with a mean age at death of (63.41±11.81) years. No statistically significant differences were observed in the proportion of hepatitis C-attributed deaths across different subgroups (all P>0.05). The proportion of premature deaths was 55.88% (114/204), with a mean age at death of (60.02±6.89) years. The proportion of premature deaths was higher among males (60.27%), laboratory-diagnosed patients (62.69%), patients with other liver diseases (72.06%), and those non-compliant with follow-up (70.97%) compared to their respective counterparts (all P<0.05). Additionally, homemakers /unemployed patients (100.00%) and employed patients (88.89%) had a significantly higher proportion of premature deaths compared to retired patients (42.67%) (P<0.001). There was a statistically significant difference in the distribution of causes of death between the premature death group and the non-premature death group (χ²=14.93， P=0.048). The top three causes of premature deaths were malignant tumors (50.00%), hepatitis C (12.28%) and cerebrovascular diseases (10.53%). Regarding the proportion of deaths occuring prematurely, other viral hepatitis had the highest percentage (75.00%), followed by diabetes mellitus (71.43%) and hepatitis C (70.00%). ConclusionThe majority of death cases with hepatitis C were males and retirees in Hongkou District, Shanghai. The leading cause of death was malignant tumors, while hepatitis C ranked as the fourth underlying cause, as well as served as the second leading cause of premature death following malignant tumors. Premature death was closely associated with gender, occupation, diagnostic classification, presence of other liver diseases, and follow-up compliance, highlighting the importance of enhanced health management and targeted interventions among high-risk groups.

BACKGROUND:In recent years,human pluripotent stem cell derived kidney organoids and rodent models of diabetic kidney disease have also made some progress.However,because the pathogenesis of diabetic kidney disease is affected by environmental factors and genetic factors,the pathogenesis is complex,and the clinical treatment for diabetic kidney disease patients needs to vary from person to person.Therefore,more flexible and integrated approaches need to be developed,leading to the discovery of strong preclinical evidence to support more targeted interventions in patients with diabetic kidney disease.OBJECTIVE:To reviewthe research progress of diabetic kidney disease model from the aspects of diabetic kidney disease animal model,two-dimensional cell culture simulation diabetic kidney disease model,and three-dimensional organoid diabetic kidney disease model,to provide clues and ideas for further research.METHODS:China National Knowledge Network and PubMed databases were searched with"diabetes,diabetic nephropathy,diabetic kidney diseases,diabetic nephropathy models,diabetic nephropathy animal models,organoids,diabetic and organoids,diabetic and kidney organoids,kidney organoids,diabetic nephropathy cell models,diabetic nephropathy syndrome combined animal models"as Chinese and English search terms.Totally 101 articles were finally included for review and analysis.RESULTS AND CONCLUSION:Both in vivo and in vitro models of diabetic kidney disease are powerful tools to further study the pathogenesis of diabetic kidney disease.The interactions between multiple systems can be observed in animal models.Two-dimensional cell culture is easy to operate and low cost.The emerging kidney organoids fill the gap between two-dimensional and global levels,without species differences,and simulate the complexity of human kidney to a certain extent.With the continuous development of organoid technology,kidney organoids are expected to provide a new perspective for exploring the pathogenesis,pathophysiology,and drug screening of diabetic kidney disease.

BACKGROUND:In recent years,human pluripotent stem cell derived kidney organoids and rodent models of diabetic kidney disease have also made some progress.However,because the pathogenesis of diabetic kidney disease is affected by environmental factors and genetic factors,the pathogenesis is complex,and the clinical treatment for diabetic kidney disease patients needs to vary from person to person.Therefore,more flexible and integrated approaches need to be developed,leading to the discovery of strong preclinical evidence to support more targeted interventions in patients with diabetic kidney disease.OBJECTIVE:To reviewthe research progress of diabetic kidney disease model from the aspects of diabetic kidney disease animal model,two-dimensional cell culture simulation diabetic kidney disease model,and three-dimensional organoid diabetic kidney disease model,to provide clues and ideas for further research.METHODS:China National Knowledge Network and PubMed databases were searched with"diabetes,diabetic nephropathy,diabetic kidney diseases,diabetic nephropathy models,diabetic nephropathy animal models,organoids,diabetic and organoids,diabetic and kidney organoids,kidney organoids,diabetic nephropathy cell models,diabetic nephropathy syndrome combined animal models"as Chinese and English search terms.Totally 101 articles were finally included for review and analysis.RESULTS AND CONCLUSION:Both in vivo and in vitro models of diabetic kidney disease are powerful tools to further study the pathogenesis of diabetic kidney disease.The interactions between multiple systems can be observed in animal models.Two-dimensional cell culture is easy to operate and low cost.The emerging kidney organoids fill the gap between two-dimensional and global levels,without species differences,and simulate the complexity of human kidney to a certain extent.With the continuous development of organoid technology,kidney organoids are expected to provide a new perspective for exploring the pathogenesis,pathophysiology,and drug screening of diabetic kidney disease.

Objective To explore the effect of nicotinamide transmethylase on intracellular reactive oxygen species(ROS)in iron death of hepatocellular carcinoma cells and its mechanism.Methods Methyl nicotinamide(MNA)expression in cells was detected using a tandem liquid chromatography-mass spectrometry.The average fluorescence intensity of ROS and lipid peroxidation was measured using a flow cytometer.Western blot was used to detect changes in the expression of human liver cancer cells(SK-Hep-1,Hep3B).Forty patients with primary hepatocellular carcinoma who received treatment in our hospital from March 2019 to February 2020 were selected as the study subjects,and their adjacent tissue samples and liver cancer tissue samples were collected.Immunohistochemical methods were used to detect the levels of nicotinamide N-methyltransferase(NNMT)and ROS in adjacent and liver cancer tissues.CCK-8 method was used to detect the survival activity of cells with different iron concentrations.Results The MNA levels in the liver cancer tissue group were higher than those in the adjacent tissue group(P<0.05).Compared with the adjacent tissue group,the average fluorescence intensity expression of ROS in the liver cancer tissue group increased,while the average fluorescence intensity expression of lipid peroxidation decreased(P<0.05).Compared with the adjacent tissue group,the expression levels of SK Hep-1 and Hep3B cells in the liver cancer tissue group increased(P<0.05).Compared with the control group,NNMT groups 2,10,20,and 25 μmol/L The cell survival activity level increased(P<0.05);Compared with the NNMT group,the iron inhibition group had different iron concentrations(2μmol/L,10μmol/L,20μmol/L,25μmol/L.The expression of cell viability decreased(P<0.05).Conclusion ROS mediated by nicotinamide methyltransferase can be guided to produce ROS and energy disorders,leading to increased tumor cell death.

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.
Mice ; Animals ; Cementogenesis ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism* ; RNA, Long Noncoding/genetics* ; Parathyroid Hormone ; Receptors, G-Protein-Coupled/metabolism*

Infertility has become a serious disease since it affects 10%-15% of couples worldwide, and male infertility contributes to about 50% of the cases. Notably, a significant decrease occurs in the newborn population by 7.82 million in 2020 compared to 2016 in China. As such, it is essential to explore the effective methods of obtaining functional male gametes for restoring male fertility. Stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), spermatogonial stem cells (SSCs), and mesenchymal stem cells (MSCs), possess the abilities of both self-renewal and differentiation into germ cells. Significantly, much progress has recently been achieved in the generation of male germ cells in vitro from various kinds of stem cells under the specified conditions, e.g., the coculturing with Sertoli cells, three-dimensional culture system, the addition of growth factors and cytokines, and/or the overexpression of germ cell-related genes. In this review, we address the current advance in the derivation of male germ cells in vitro from stem cells based on the studies of the peers and us, and we highlight the perspectives and potential application of stem cell-derived male gametes in reproductive medicine.
Humans ; Infant, Newborn ; Male ; Germ Cells ; Embryonic Stem Cells ; Cell Differentiation ; Infertility, Male ; Induced Pluripotent Stem Cells

Spermatogonial stem cells (SSCs) have great applications in both reproductive and regenerative medicine. Primates including monkeys are very similar to humans with regard to physiology and pathology. Nevertheless, little is known about the isolation, the characteristics, and the culture of primate SSCs. This study was designed to identify, isolate, and culture monkey SSCs. Immunocytochemistry was used to identify markers for monkey SSCs. Glial cell line-derived neurotrophic factor family receptor alpha-1 (GFRA1)-enriched spermatogonia were isolated from monkeys, namely Macaca fascicularis (M. fascicularis), by two-step enzymatic digestion and magnetic-activated cell sorting, and they were cultured on precoated plates in the conditioned medium. Reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, and RNA sequencing were used to compare phenotype and transcriptomes in GFRA1-enriched spermatogonia between 0 day and 14 days of culture, and xenotransplantation was performed to evaluate the function of GFRA1-enriched spermatogonia. SSCs shared some phenotypes with rodent and human SSCs. GFRA1-enriched spermatogonia with high purity and viability were isolated from M. fascicularis testes. The freshly isolated cells expressed numerous markers for rodent SSCs, and they were cultured for 14 days. The expression of numerous SSC markers was maintained during the cultivation of GFRA1-enriched spermatogonia. RNA sequencing reflected a 97.3% similarity in global gene profiles between 0 day and 14 days of culture. The xenotransplantation assay indicated that the GFRA1-enriched spermatogonia formed colonies and proliferated in vivo in the recipient c-Kit

Objective To evaluate the role of microglia in paraventricular nucleus (PVN) in sus-ceptibility to depression in rats with chronic visceral pain. Methods Ninety-six pathogen-free healthy male Sprague-Dawley rats, aged 8 days, were divided into 6 groups (n= 16 each) using a random number table: sham operation group (S group), chronic visceral pain group (CHVP group), sham operation plus colorectal distension group (S+C group), chronic visceral pain plus colorectal distension group (CHVP+C group), chronic visceral pain plus phosphate buffer solution plus colorectal distension group (CHVP+P+C group) and chronic visceral pain plus minocycline plus colorectal distension group (CHVP+M+C group). Colorectal distension was not performed in S group. In CHVP group, chronic visceral pain was induced by performing colorectal distension twice daily on postnatal days 8, 10, and 12. Phosphate buffer solution 0. 5μl was injected into PVN by stereotaxic method at 8th week after birth in CHVP+P+C group, and 2％ mi-nocycline 0. 5 μl was injected into PVN at 8th week after birth in CHVP+M+C group. Eight rats in each group were selected 2 h later for measurement of visceral pain threshold. In S+C, CHVP+C, CHVP+P+C and CHVP+M+C groups, colorectal distension was performed for 2 times, open field test and sucrose preference test were then performed, the rats were sacrificed and PVN was removed for determination of micro-glial activation by immunofluorescence. Results The pain threshold was significantly decreased in CHVP, CHVP+C, CHVP+P+C and CHVP+M+C groups as compared with S and S+C groups (P<0. 05). The pain threshold was significantly increased in CHVP+M+C group when compared with CHVP +P +C group (P<0. 05). Compared with S, CHVP and S+C groups, the total locomotor distance, the number of rea-ring and sucrose consumption were significantly reduced, and the proportion of activated microglia in PVN was increased in CHVP+C, CHVP+P+C and CHVP+M+C groups (P<0. 05). Compared with CHVP+P+C group, the total locomotor distance, the number of rearing and sucrose consumption were significantly in-creased, and the proportion of activated microglia in PVN was decreased in CHVP+M+C group (P<0. 05). Conclusion Microglia in PVN is involved in regulation of susceptibility to depression in rats with chronic visceral pain.

Objective To explore 3D constructive interference insteady state sequence value of related diseases in trigeminal neuralgia.Methods A retrospective analysis of 62 cases of trigeminal neuralgia as the main symptoms of patients with brain magnetic resonance imaging (MRI) routine scan and 3D constructive interference insteady state (3D-CISS) sequence images,of which 12 cases were enhanced scan,comparative analysis of MRI 3D-CISS sequence and conventional sequence of trigeminal nerve.The lesion showed the condition and was compared with the outcome of the operation.Trigeminal neuralgia-related lesions mainly included the trigeminal nerve brain pool around the vascular compression or transition,solid tumors and tumor-like lesions.Results Preoperative MRI 3D-CISS sequence was used to diagnose the vascular compression or metastasis of the trigeminal nerve pool segment in 46 cases.Forty-five patients were found to be responsible blood vessels.The 3D-CISS sequence showed 95.83％ coincidence with surgical exploration.The routine sequence could not show the trigeminal The brain around the brain was forced or pushed.3D-CISS sequence showed eight cases of solid tumors,routine scan showed six cases of solid tumors.Tumor-like lesions were shown in 6 cases of MRI3D-CISS sequences and routine plain scan sequences.The sensitivity of 3D-CISS sequence to trigeminal neuralgia-related disease was 96.77％,and the sensitivity of MRI routine scan to trigeminal neuralgia was only 19.35％.There was significant difference in the sensitivity of 3D-CISS sequence and conventional plain scan sequence to trigeminal neuralgia-related diseases (P ＜ 0.01).Conclusions MRI 3D-CISS sequence has a significant advantage in trigeminal neuralgia-related disease,and patients with trigeminal neuralgia should routinely use 3D-CISS sequences.

People′s misunderstandings about the radiological check in health examination: Equalize the price of the medical check equipment with the accuracy of the check .The health examinees′misunderstanding about the harm which X-Ray can cause , thinking that low dose chest CT only can do very little harm to human body .The health examination unit makes the rate of finding out early lung tumor a main basis of assessing a medical personnel ′s achievement , which caused medical staff go against epidemiological laws when diagnosing tiny nodules .Misun-derstandings about some biological features such as the scale or the growing speed of the nidus , and laying exces-sive importance on the check accuracy , which caused some examinees received excessive X -Ray, overdiagnosis and overtreatment .So, people must treat radiological check in health examination rationally and dialectically , in order to further realize the legitimation and rationalization of radiological check .