ObjectiveTo investigate the etiology and clinical features of intrahepatic cholestasis and the diagnostic value of whole exome sequencing （WES） through a retrospective analysis of the medical history， pathological results， and gene sequencing data of 62 patients with unexplained intrahepatic cholestasis. MethodsA retrospective analysis was performed for the clinical data of 480 patients who underwent WES due to unexplained liver function abnormalities in Nanjing Second Hospital from January 2017 to December 2023， among whom 62 patients with unexplained intrahepatic cholestasis were selected based on laboratory data， and a confirmed diagnosis was made based on imaging data， pathological findings， and gene sequencing data. The patients with unexplained intrahepatic cholestasis were analyzed in terms of demographic features， clinical manifestation， etiology spectrum， and genetic profile. ResultsA total of 62 patients with unexplained intrahepatic cholestasis were included， among whom there were 35 male patients and 27 female patients， with a median age of 42 （7 — ‍77） years. WES was used to make a definite diagnosis in 21 patients （33.87%）， among whom the patients with familial intrahepatic cholestasis accounted for the highest proportion of 52.38% （11/21）； genetic metabolic disorders were excluded by WES in 34 patients， with drug-induced liver injury and sepsis-associated liver injury accounting for the highest proportion of 55.88% （19/34）， followed by primary biliary cholangitis and primary sclerosing cholangitis accounting for 20.59% （7/34） and intrahepatic bile duct stones accounting for 17.65% （6/34）， while the patients with a lack of confirmed diagnosis accounted for 11.29% （7/62）. A total of 21 novel mutation sites which were not reported in previous articles were identified in this study. ConclusionGenetic metabolic disorders constitute a significant proportion of unexplained intrahepatic cholestasis， and WES plays a crucial role in the diagnosis of unexplained intrahepatic cholestasis.

Objective To investigate and analyze epidemiological characteristics of patients with mycoplasma pneumoniae pneumonia (MPP) from 2020 to 2023, and the risk factors for plastic bronchitis (PB), To provide data support for developing preventive measures. Methods The medical records of 2 257 patients with respiratory tract infection treated at Huai'an Hospital Affiliated to Xuzhou Medical University from 2020 to 2023 were collected. Count the number of MPP patients and analyze the MP detection rate. Multivariate logistic regression analysis and ROC curve was used to screen the risk factors for PB. Results A total of 858 cases were positive for MP antibodies, and the detection rate was 38.02%. There are statistically significant differences in MP detection rates among different genders, age groups, and years (P<0.05). Among the 286 patients diagnosed with MPP and undergoing bronchoscopy, 68 (23.78%) patients had PB. According to univariate and multivariate logistic regression analysis, small age, higher N%, D-D, LDH and AST levels were independent risk factors for PB (P<0.05). ROC curve analysis shows that age and combined detection are the most effective indicators for PB prediction, with areas under the curve of 0.998 and 0.961, respectively. Conclusion MP is the main pathogen of respiratory tract infections in the area from 2020 to 2023. Women and children are more susceptible to MP infection. Small age, high N%, DD, LDH and AST levels are independent risk factors for PB in patients with MPP. Targeted preventive measures should be taken for MP susceptible population, and close attention should be paid to PB related risk factors to prevent disease progression and the occurrence of PB.

Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death.It was previously thought that myocardial cells of the adult mammalian heart possess a limited ability to proliferate and self-renew.However,it has been widely reported that mammals have the ability to regenerate the myocardium,which is restricted to early postnatal life,and that it is strong enough to repair damaged heart tissue.The discovery of myocardial regeneration in neonatal hearts has provided an ideal animal model to investigate the mechanisms that affect myocardial regeneration,and many mechanisms that reverse myocardial cell cycle arrest and promote myocardial regeneration have been revealed.In this article,we review the factors affecting gene expression for myocardial regeneration(e.g.,ncRNAs and transcription factors),myocardial regeneration-related signaling pathways,and the regulation of myocardial regeneration by non-myocardial cells(e.g.,extracellular matrix,immune response,and epicardium)to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.

Objective To explore the clinicopathological and immunohistochemical features of nephrogenic adenoma(NA).Methods Clinical data of NA patients diagnosed in the Department of Pathology,Zhongshan Hospital,Fudan University from July 2016 to October 2022 were collected and analyzed to explore their clinicopathological features.Results A total of 13 NA cases were enrolled.There were 11 males and 2 females.Organs involved:ureter(n=7),bladder(n=5),bladder and ureter(n=1),renal pelvis(n=2).NA patients performed as ureteral stenosis(6/7),rough bladder wall(3/5),and renal pelvis polyp(2/2).The typical microscopical features of NA were tubular(13/13)and papillary(4/13)structures,covered with cuboidal or columnar epithelium(13/13),or a mixed hobnail-spike eosinophilic epithelium(12/13);the interstitium was loose,containing varied amounts of vasculature and inflammatory cells(13/13).Immunohistochemistry revealed specific expressions of CK7,PAX-8,CK19 and CK8.Conclusions NA is a rare neoplasm of the urinary system with unique histological features.NA has the risk of misdiagnosis and over-treatment,and the potential of recurrence and malignant conversion.The diagnosis of NA depends on pathology,and the immunohistochemistry can be helpful for its pathological diagnosis.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Objective:To study the expression level of peripheral blood microRNA(miRNA)-21 and miRNA-192 in patients with papillary thyroid carcinoma (PTC) and their relationship with pathological features and prognosis.Methods:A total 107 PTC patients admitted to Huaian Cancer Hospital in Jiangsu Province from June 2018 to June 2021 were selected as the PTC group, another 76 healthy individuals who underwent physical examination during the same period were selected as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) was used to measure the expression levels of miRNA-21 and miRNA-192 in the peripheral blood of two populations, and the expression of miRNA-21 and miRNA-192 in the peripheral blood of the two populations and patients with different characteristics was compared and analyzed. Kaplan-Meier (K-M) method was used to analyze the relationship between the expression levels of miRNA-21, miRNA-192 in peripheral blood of PTC patients and prognosis.Results:The expression level of miRNA-21 in the peripheral blood of patients in the PTC group (2.21 ± 0.64) was higher than that in the control group (1.01 ± 0.02), while miRNA-192 (0.42 ± 0.14) was lower than that in the control group (0.99 ± 0.03, t = 16.33, 34.90, P < 0.001). In different clinical stages, the expression level of miRNA-21 in peripheral blood of patients in stages Ⅲ - Ⅳ was higher than that in stages Ⅰ - Ⅱ, and the level of miRNA-192 was lower than that in stages Ⅰ - Ⅱ ( t = 9.98, 11.75, P < 0.001). In the case of lymph node metastasis, the expression level of miRNA-21 in peripheral blood of patients with lymph node metastasis was higher than that of the group without lymph node metastasis, and the level of miRNA-192 was lower than that of the group without lymph node metastasis ( t = 12.81, 18.75, P < 0.001). There was no statistically significant difference in the expression levels of miRNA-21 and miRNA-192 in peripheral blood of patients with different genders, ages, body mass index, and tumor sizes ( t = 0.57, 0.42, 0.54, 0.62, 1.15, 1.47, 0.74, 1.13, P > 0.05). The K-M survival curve results showed that the progression free survival time (39.02 months) with high miRNA-21 expression was lower than that with low miRNA-21 expression (55.97 months, P = 0.026); the progression free survival time (34.97 months) with low miRNA-192 expression was lower than that with high miRNA-192 expression (57.04 months, P = 0.008). Conclusion:The high expression of miRNA-21 and low expression of miRNA-192 in peripheral blood of PTC patients, and they are closely related to the clinical stage, lymph node metastasis, and prognosis of patients.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective:To investigate the incidence and mortality of gynecological tumors in China from 1990 to 2019, and explore the impact of age, period and birth cohort on the incidence and mortality of gynecological tumors, and predict the incidence and mortality trends of gynecological tumors, so as to provide references for formulating the prevention and control strategies of gynecological tumors.Methods:Based on the Global Burden of Disease Study 2019 (GBD 2019) database, the Joinpoint regression model was used to analyze the change trends of standardized incidence rates and mortality rates of cervical cancer, uterine cancer and ovarian cancer in China. The age, period and cohort effects of the incidence and mortality of 3 gynecological tumors were analyzed by using R software based on age-period-cohort model. The grey forecast model (GM) (1, 1) was used to fit the trends of incidence rates and mortality rates of 3 gynecological tumors, and predict the incidence rates and mortality rates from 2020 to 2034.Results:From 1990 to 2019, the standardized incidence rates of cervical cancer, uterine cancer and ovarian cancer showed upward trends in China, the standardized incidence rates increased from 8.41/100 000, 5.13/100 000 and 2.56/100 000 in 1990 to 11.01/100 000, 6.39/100 000 and 4.54/100 000 in 2019, the average annual percent changes (AAPC) were 0.9 % (95% CI: 0.8%-1.1%), 0.8 % (95% CI: 0.6%-1.0%) and 2.0 % (95% CI: 1.9%-2.1%), respectively, and the differences were statistically significant (all P < 0.001). The standardized mortality rate of ovarian cancer showed an increasing trend year by year, the standardized mortality rate increased from 1.76/100 000 in 1990 to 2.77/100 000 in 2019, with the AAPC of 1.6 % (95% CI: 1.4%-1.7%), while the standardized mortality rates of uterine cancer and cervical cancer showed decreasing trends year by year, the standardized mortality rates decreased from 2.38/100 000 and 5.85/100 000 in 1990 to 1.17/100 000 and 5.13/100 000 in 2019, with the AAPC of -2.4 % (95% CI: -2.6% - -2.3%) and -0.4 % (95% CI: -1.6% - -0.3%), respectively, and the differences were statistically significant (both P < 0.001).The analysis of age effect showed that the incidence rates and mortality rates of cervical cancer, uterine cancer and ovarian cancer showed gradual upward trends with age, reaching a peak in the ≥85 years old group. The analysis of period effect showed that the incidence risk of cervical cancer and uterine cancer decreased firstly, then increased and then decreased, and the incidence risk of cervical cancer and uterine cancer was the highest in 1990-1994 ( RR = 1.04, 95% CI: 0.86-1.27) and 2005-2009 ( RR = 1.08, 95% CI: 0.88-1.31), respectively. The incidence risk of ovarian cancer increased firstly and then decreased, and the incidence risk of ovarian cancer was the highest in 2000-2004 ( RR = 0.96, 95% CI: 0.71-1.30). The mortality risk of cervical cancer showed a trend of decreasing firstly, then increased and then decreased, and the mortality risk was the highest in 1990-1994 ( RR = 1.22, 95% CI: 0.86-1.27). The mortality risk of uterine cancer showed a trend of decreasing year by year, and the mortality risk was the highest in 1990-1994 ( RR = 1.26, 95% CI: 0.85-1.87). The mortality risk of ovarian cancer showed a trend of increasing firstly and then decreased, and the mortality risk was the highest in 1990-1994 ( RR = 1.01, 95% CI: 0.69-1.48). Cohort effect analysis showed that the risk of incidence and mortality of cervical cancer, uterine cancer and ovarian cancer showed a gradually decreasing trend except for a small fluctuation in individual birth cohorts, but the birth cohort 1990-1994 showed a rebound trend. The GM results showed that the overall incidence rates of cervical cancer, uterine cancer and ovarian cancer in China were increased year by year. In addition to the mortality rate of uterine cancer at a stable level, the mortality rates of cervical cancer and ovarian cancer showed upward trends. Conclusions:The disease burden of gynecological tumors in China is still heavy. Age, period and birth cohort effects affect the incidence and mortality of cervical cancer, uterine cancer and ovarian cancer to varying degrees.

Purpose: To analyze the gene mutation, immune infiltration and tumor growth of primary tumor and distant tumor under different treatment modes. Materials and Methods: Twenty B16 murine melanoma cells were injected subcutaneously into the of both sides of the thigh, simulating a primary tumor and a secondary tumor impacted by the abscopal effect, respectively. They were divided into blank control group, immunotherapy group, radiotherapy group, and radiotherapy combined immunotherapy group. During this period, tumor volume was measured, and RNA sequencing was performed on tumor samples after the test. R software was used to analyze differentially expressed genes, functional enrichment, and immune infiltration. Results: We found that any treatment mode could cause changes in differentially expressed genes, especially the combination treatment. The different therapeutic effects might be caused by gene expression. In addition, the proportions of infiltrating immune cells in the irradiated and abscopal tumors were different. In the combination treatment group, T-cell infiltration in the irradiated site was the most obvious. In the immunotherapy group, CD8+ T-cell infiltration in the abscopal tumor site was obvious, but immunotherapy alone might have a poor prognosis. Whether the irradiated or abscopal tumor was evaluated, radiotherapy combined with anti-programmed cell death protein 1 (anti-PD-1) therapy produced the most obvious tumor control and might have a positive impact on prognosis. Conclusion Combination therapy not only improves the immune microenvironment but may also have a positive impact on prognosis.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled